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Clinical Trial Results:
A phase 3 randomized, open-label (sponsor-blind), active controlled, parallel-group, multi-center, event driven study in dialysis subjects with anemia associated with chronic kidney disease to evaluate the safety and efficacy of daprodustat compared to recombinant human erythropoietin, following a switch from erythropoietin-stimulating agents

Summary
EudraCT number	2016-000541-31
Trial protocol	HU BE GB DK CZ DE SE PT ES NL AT GR FR IT
Global end of trial date	09 Nov 2020

Results information
Results version number	v1(current)
This version publication date	20 Nov 2021
First version publication date	20 Nov 2021
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

200807

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom, TW8 9GS

Public contact

GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

15 Apr 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

09 Nov 2020

Was the trial ended prematurely?

Main objective of the trial

• To compare daprodustat to recombinant human erthropoetin (rhEPO) for cardiovascular (CV) safety (non-inferiority) • To compare daprodustat to rhEPO for hemoglobin (Hgb) efficacy (non-inferiority)

Protection of trial subjects

Not applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

28 Sep 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

India: 70

Country: Number of subjects enrolled

Malaysia: 31

Country: Number of subjects enrolled

Singapore: 12

Country: Number of subjects enrolled

Korea, Republic of: 129

Country: Number of subjects enrolled

Taiwan: 43

Country: Number of subjects enrolled

Bulgaria: 80

Country: Number of subjects enrolled

Czechia: 50

Country: Number of subjects enrolled

Estonia: 11

Country: Number of subjects enrolled

Hungary: 143

Country: Number of subjects enrolled

Poland: 73

Country: Number of subjects enrolled

Romania: 37

Country: Number of subjects enrolled

Russian Federation: 207

Country: Number of subjects enrolled

South Africa: 47

Country: Number of subjects enrolled

Turkey: 24

Country: Number of subjects enrolled

Ukraine: 163

Country: Number of subjects enrolled

Australia: 56

Country: Number of subjects enrolled

Austria: 12

Country: Number of subjects enrolled

Belgium: 39

Country: Number of subjects enrolled

Canada: 11

Country: Number of subjects enrolled

Denmark: 23

Country: Number of subjects enrolled

France: 27

Country: Number of subjects enrolled

Germany: 43

Country: Number of subjects enrolled

Greece: 96

Country: Number of subjects enrolled

Italy: 34

Country: Number of subjects enrolled

Netherlands: 6

Country: Number of subjects enrolled

New Zealand: 44

Country: Number of subjects enrolled

Norway: 6

Country: Number of subjects enrolled

Portugal: 64

Country: Number of subjects enrolled

Spain: 81

Country: Number of subjects enrolled

Sweden: 4

Country: Number of subjects enrolled

United Kingdom: 26

Country: Number of subjects enrolled

Argentina: 182

Country: Number of subjects enrolled

Brazil: 156

Country: Number of subjects enrolled

Mexico: 88

Country: Number of subjects enrolled

United States: 846

Worldwide total number of subjects

2964

EEA total number of subjects

829

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

1985

From 65 to 84 years

931

85 years and over

Subject disposition

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Recruitment details

This was a randomized, open-label (sponsor blind), active-controlled, parallel-group, event-driven study conducted at 431 centers in 35 countries. Participants were randomized to receive daprodustat and recombinant human erythropoietin (rhEPO) (epoetin alfa or darbepoetin alfa).

Screening details

A total of 2964 participants were randomized in the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Daprodustat

Arm description

Participants received placebo tablets orally once daily in run-in period from Week -4 up to randomization (Day 1) and subsequently received daprodustat tablets at dose levels of 1, 2, 4, 6, 8, 10, 12, 16 and 24 milligrams (mg) orally once daily until the required number of major adverse cardiovascular event (MACE) occurred, at approximately 45.1 months of randomized treatment. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (10 to 11 grams per deciliter [g/dL]).

Arm type

Experimental

Investigational medicinal product name

Daprodustat

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Daprodustat was given orally once daily at dose levels ranging from 1, 2, 4, 6, 8, 10, 12, 16 and 24 milligrams (mg).

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo was administered orally, one tablet daily.

rhEPO

Arm description

Participants received placebo tablets orally once daily in run-in period from Week -4 up to randomization (Day 1) and subsequently received treatment with rhEPO. Participants on hemodialysis received epoetin alfa as intravenous (IV) injection once weekly or three-times weekly with total weekly dose levels ranging from 1500 to 60,000 Units. Participants on peritoneal dialysis received subcutaneous (SC) injection of darbepoetin alfa every 1, 2, or 4 weeks with 4-weekly total dose levels ranging from 20 to 400 microgram (mcg). Darbepoetin could be given by IV injection for peritoneal dialysis participants switching to hemodialysis. Study treatment was dose-titrated to achieve and maintain hemoglobin in the target range (10 to 11 g/dL) and administered until the required number of MACE events occurred, at approximately 45.1 months of randomized treatment.

Arm type

Active comparator

Investigational medicinal product name

Epoetin alfa

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Epoetin alfa was administered as once weekly or three-times weekly intravenous (IV) injection at total weekly dose levels ranging from 1500 to 60,000 Units .

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo was administered orally, one tablet daily.

Investigational medicinal product name

Darbepoetin alfa

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection, Solution for injection in pre-filled syringe

Routes of administration

Intravenous use, Subcutaneous use

Dosage and administration details

Darbepoetin alfa was administered subcutaneously (SC) or as IV injection with 4-weekly total dose levels ranging from 20, 30, 40, 60, 80, 100, 150, 200, 300 and 400 microgram (mcg).

Number of subjects in period 1	Daprodustat	rhEPO
Started	1487	1477
Completed	1370	1366
Not completed	117	111
Consent withdrawn by subject	44	42
Investigator Site Closed	55	57
Unknown	1	-
Lost to follow-up	17	12

Baseline characteristics

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Reporting group title

Daprodustat

Reporting group description

Reporting group title

rhEPO

Reporting group description

Reporting group values	Daprodustat	rhEPO	Total
Number of subjects	1487	1477	2964
Age categorical
All Randomized (Intent-to-treat [ITT]) Population comprised of all randomized participants. Participants were analyzed according to the treatment to which they were randomized.
Units: Participants
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	1007	978	1985
From 65-84 years	458	473	931
85 years and over	22	26	48
Age Continuous
All Randomized (Intent-to-treat [ITT]) Population comprised of all randomized participants. Participants were analyzed according to the treatment to which they were randomized.
Units: years
arithmetic mean (standard deviation)	57.2 ± 14.29	57.3 ± 14.65	-
Sex: Female, Male
All Randomized (Intent-to-treat [ITT]) Population comprised of all randomized participants. Participants were analyzed according to the treatment to which they were randomized.
Units: Participants
Female	636	630	1266
Male	851	847	1698
Race/Ethnicity, Customized
All Randomized (Intent-to-treat [ITT]) Population comprised of all randomized participants. Participants were analyzed according to the treatment to which they were randomized.
Units: Subjects
American Indian or Alaskan Native	19	32	51
Asian - Central/South Asian Heritage	36	46	82
Asian - East Asian Heritage	97	86	183
Asian - Japanese Heritage	3	3	6
Asian - South East Asian Heritage	40	45	85
Black or African American	228	233	461
Native Hawaiian or Other Pacific Islander	26	25	51
White - Arabic/North African Heritage	8	14	22
White - White/Caucasian/European Heritage	987	968	1955
Mixed Asian Race	0	1	1
Mixed Race	43	24	67

End points

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Reporting group title

Daprodustat

Reporting group description

Reporting group title

rhEPO

Reporting group description

Primary: Time to first occurrence of adjudicated major adverse cardiovascular event (MACE) during cardiovascular (CV) events follow-up time period: Non-inferiority analysis

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End point title

Time to first occurrence of adjudicated major adverse cardiovascular event (MACE) during cardiovascular (CV) events follow-up time period: Non-inferiority analysis

End point description

Time to MACE defined as time to first occurrence of Clinical Events Committee (CEC) adjudicated MACE (composite of all-cause mortality, non-fatal myocardial infarction [MI] and non-fatal stroke) was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to first occurrence was computed as (event date minus randomization date)+1. Incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95 percent (%) confidence interval (CI). First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. All Randomized (Intent-to-treat [ITT]) Population comprised of all randomized participants. Participants were analyzed according to the treatment to which they were randomized.

End point type

Primary

End point timeframe

Up to 3.9 person-years for CV follow-up time period

End point values	Daprodustat	rhEPO
Number of subjects analysed	1487 ^[1]	1477 ^[2]
Units: Events per 100 person years
number (confidence interval 95%)	11.07 (9.98 to 12.26)	11.86 (10.72 to 13.09)

Notes
[1] - All Randomized (ITT) Population
[2] - All Randomized (ITT) Population

Statistical analysis

Statistical analysis description

Hazard ratio was estimated using a Cox proportional hazard regression model with treatment group, dialysis type and region as covariates.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.07

Notes
[3] - Non-inferiority was achieved if the upper limit of the two-sided 95% CI for the hazard ratio was below the pre-specified non-inferiority margin of 1.25.

Primary: Mean Change from Baseline in Hemoglobin (Hgb) levels During Evaluation Period (Week 28 to Week 52)

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End point title

Mean Change from Baseline in Hemoglobin (Hgb) levels During Evaluation Period (Week 28 to Week 52)

End point description

Blood samples were collected from participants for hemoglobin measurements. Hemoglobin during the evaluation period was defined as the mean of all available post-randomization hemoglobin values (on and off-treatment) during the evaluation period (Week 28 to Week 52). For the primary analysis, missing post-Baseline hemoglobin values were imputed using pre-specified multiple imputation methods. Change from Baseline was defined as post-Baseline value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.

End point type

Primary

End point timeframe

Baseline (Pre-dose on Day 1) and evaluation period (Week 28 to Week 52)

End point values	Daprodustat	rhEPO
Number of subjects analysed	1487 ^[4]	1477 ^[5]
Units: Grams per deciliter
least squares mean (standard error)	0.28 ± 0.022	0.10 ± 0.022

Notes
[4] - All Randomized (ITT) Population
[5] - All Randomized (ITT) Population

Statistical analysis

Statistical analysis description

Analysis of covariance (ANCOVA) model adjusted for treatment, Baseline Hgb, dialysis type and region along with 95% CI for treatment difference (daprodustat-rhEPO).

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[6]

Method

Parameter type

Least square (LS) mean difference

Point estimate

0.18

Confidence interval

level

95%

sides

2-sided

lower limit

0.12

upper limit

0.24

Notes
[6] - Non-inferiority was to be established if the lower limit of the two-sided 95% CI for the treatment difference was greater than -0.75 g/dL.

Secondary: Time to first occurrence of adjudicated MACE during CV events follow-up time period: Superiority analysis

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End point title

Time to first occurrence of adjudicated MACE during CV events follow-up time period: Superiority analysis

End point description

Time to MACE defined as the time to first occurrence of CEC adjudicated MACE was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariate. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method.

End point type

Secondary

End point timeframe

Up to 3.9 person-years for CV follow-up time period

End point values	Daprodustat	rhEPO
Number of subjects analysed	1487 ^[7]	1477 ^[8]
Units: Events per 100 person years
number (confidence interval 95%)	11.07 (9.98 to 12.26)	11.86 (10.72 to 13.09)

Notes
[7] - All Randomized (ITT) Population
[8] - All Randomized (ITT) Population

Statistical analysis

Statistical analysis description

Hazard ratio was estimated using a Cox proportional hazard regression model with treatment group, dialysis type and region as covariates.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.156123 ^[9]

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.07

Notes
[9] - The p-value was compared against 0.0125 based on the Holm-Bonferonni adjustment.

Secondary: Time to first occurrence of adjudicated MACE or thromboembolic event during CV events follow-up time period

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End point title

Time to first occurrence of adjudicated MACE or thromboembolic event during CV events follow-up time period

End point description

Time to first occurrence of adjudicated MACE or thromboembolic event (vascular access thrombosis, symptomatic deep vein thrombosis or symptomatic pulmonary embolism) was analyzed using a Cox proportional hazards regression model with with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method.

End point type

Secondary

End point timeframe

Up to 3.9 person-years for CV follow-up time period

End point values	Daprodustat	rhEPO
Number of subjects analysed	1487 ^[10]	1477 ^[11]
Units: Events per 100 person years
number (confidence interval 95%)	15.84 (14.48 to 17.30)	17.85 (16.38 to 19.42)

Notes
[10] - All Randomized (ITT) Population.
[11] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Hazard ratio was estimated using a Cox proportional hazard regression model with treatment group, dialysis type and region as covariates.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.023539 ^[12]

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

Notes
[12] - The p-value was compared against 0.006250 based on the Holm-Bonferonni adjustment.

Secondary: Time to first occurrence of adjudicated MACE or hospitalization for heart failure during CV events follow-up time period

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End point title

Time to first occurrence of adjudicated MACE or hospitalization for heart failure during CV events follow-up time period

End point description

Time to first occurrence of adjudicated MACE or hospitalization for heart failure was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. This endpoint was adjusted for multiplicity using the Holm-Bonferonni method.

End point type

Secondary

End point timeframe

Up to 3.9 person-years for CV follow-up time period

End point values	Daprodustat	rhEPO
Number of subjects analysed	1487 ^[13]	1477 ^[14]
Units: Events per 100 person years
number (confidence interval 95%)	12.98 (11.77 to 14.27)	13.38 (12.15 to 14.70)

Notes
[13] - All Randomized (ITT) Population.
[14] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Hazard ratio was estimated using a Cox proportional hazard regression model with treatment group, dialysis type and region as covariates.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.325797 ^[15]

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.11

Notes
[15] - The p-value was compared against 0.025000 based on the Holm-Bonferonni adjustment.

Secondary: Mean average monthly On-treatment IV iron dose per participant

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End point title

Mean average monthly On-treatment IV iron dose per participant

End point description

Average monthly IV iron dose (milligrams) per participant from Day 1 to Week 52 was determined by calculating the total IV iron dose per participant from treatment start date + 1 to the earliest of (Week 52 visit date, first blood (red blood cell [RBC] or whole blood) transfusion date, and treatment stop date + 1 day) which corresponds to the time while the participant was on randomized treatment and before receiving a blood transfusion. This total IV iron dose was divided by (the number of days from treatment start date + 1 to the earliest of (Week 52 visit date, first blood transfusion date (RBC or whole blood), and treatment stop date +1) / 30.4375 days). This endpoint was adjusted for multiplicity using the Holm-Bonferonni method. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Day 1 to Week 52

End point values	Daprodustat	rhEPO
Number of subjects analysed	1482 ^[16]	1472 ^[17]
Units: Milligrams
least squares mean (standard error)	90.8 ± 3.34	99.9 ± 3.35

Notes
[16] - All Randomized (ITT) Population.
[17] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Analysis was carried out by using ANCOVA model with terms for treatment, Baseline monthly IV iron dose, dialysis type and region.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2954

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.026947 ^[18]

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-9.1

Confidence interval

level

95%

sides

2-sided

lower limit

-18.4

upper limit

0.2

Notes
[18] - The p-value was compared against 0.008333 based on the Holm-Bonferonni adjustment.

Secondary: Time to First occurrence of Adjudicated All-Cause Mortality during vital status for follow-up time period

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End point title

Time to First occurrence of Adjudicated All-Cause Mortality during vital status for follow-up time period

End point description

Time to first occurrence of adjudicated all-cause mortality was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the vital status for follow-up time period.

End point type

Secondary

End point timeframe

Up to 3.9 person-years for vital status follow-up time period

End point values	Daprodustat	rhEPO
Number of subjects analysed	1487 ^[19]	1477 ^[20]
Units: Events per 100 person years
number (confidence interval 95%)	8.32 (7.39 to 9.32)	8.59 (7.65 to 9.62)

Notes
[19] - All Randomized (ITT) Population.
[20] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Hazard ratio was estimated using a Cox proportional hazard regression model with treatment group, dialysis type and region as covariates.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3281

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.13

Secondary: Time to First occurrence of Adjudicated CV Mortality during CV events follow-up time period

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End point title

Time to First occurrence of Adjudicated CV Mortality during CV events follow-up time period

End point description

Time to first occurrence of adjudicated CV mortality was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.

End point type

Secondary

End point timeframe

Up to 3.9 person-years for CV follow-up time period

End point values	Daprodustat	rhEPO
Number of subjects analysed	1487 ^[21]	1477 ^[22]
Units: Events per 100 person years
number (confidence interval 95%)	3.31 (2.74 to 3.97)	3.46 (2.88 to 4.14)

Notes
[21] - All Randomized (ITT) Population.
[22] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Hazard ratio was estimated using a Cox proportional hazard regression model with treatment group, dialysis type and region as covariates.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3553

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

1.23

Secondary: Time to First occurrence of Adjudicated Myocardial Infarction (MI) (Fatal and Non-Fatal) during CV events follow-up time period

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End point title

Time to First occurrence of Adjudicated Myocardial Infarction (MI) (Fatal and Non-Fatal) during CV events follow-up time period

End point description

Time to first occurrence of adjudicated MI (fatal and non-fatal) was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.

End point type

Secondary

End point timeframe

Up to 3.9 person-years for CV follow-up time period

End point values	Daprodustat	rhEPO
Number of subjects analysed	1487 ^[23]	1477 ^[24]
Units: Events per 100 person years
number (confidence interval 95%)	3.34 (2.76 to 4.01)	4.08 (3.43 to 4.83)

Notes
[23] - All Randomized (ITT) Population.
[24] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Hazard ratio was estimated using a Cox proportional hazard regression model with treatment group, dialysis type and region as covariates.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0524

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

1.04

Secondary: Time to First occurrence of Adjudicated Stroke (Fatal and Non-Fatal) during CV events follow-up time period

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End point title

Time to First occurrence of Adjudicated Stroke (Fatal and Non-Fatal) during CV events follow-up time period

End point description

Time to first occurrence of adjudicated stroke (fatal and non-fatal) was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.

End point type

Secondary

End point timeframe

Up to 3.9 person-years for CV follow-up time period

End point values	Daprodustat	rhEPO
Number of subjects analysed	1487 ^[25]	1477 ^[26]
Units: Events per 100 person years
number (confidence interval 95%)	1.23 (0.89 to 1.66)	1.48 (1.10 to 1.94)

Notes
[25] - All Randomized (ITT) Population.
[26] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Hazard ratio was estimated using a Cox proportional hazard regression model with treatment group, dialysis type and region as covariates.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1927

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.56

upper limit

1.25

Secondary: Number of participants with Adjudicated MACE or Hospitalization for Heart Failure (Recurrent events analysis)

Top of page

End point title

Number of participants with Adjudicated MACE or Hospitalization for Heart Failure (Recurrent events analysis)

End point description

Number of participants with adjudicated MACE or hospitalization for heart failure (recurrent events analysis) is presented, categorized by number of occurrences of adjudicated MACE or hospitalization for heart failure per participant.

End point type

Secondary

End point timeframe

Up to 3.9 person-years for CV follow-up time period

End point values	Daprodustat	rhEPO
Number of subjects analysed	1487 ^[27]	1477 ^[28]
Units: Participants
Occurrences per participant: 0	1062	1044
Occurrences per participant: 1	315	300
Occurrences per participant: 2	72	88
Occurrences per participant: 3	25	22
Occurrences per participant: 4	3	11
Occurrences per participant: 5	4	4
Occurrences per participant: 6	4	3
Occurrences per participant: 7	0	2
Occurrences per participant: 8	0	1
Occurrences per participant: 9	1	1
Occurrences per participant: 10	1	1

Notes
[27] - All Randomized (ITT) Population.
[28] - All Randomized (ITT) Population.

Statistical analysis 1

Statistical analysis description

Overall HR is presented using Model 1. Model 1 assumed a common treatment effect, regardless of number of events experienced. HR was estimated using a Prentice, Williams and Peterson(PWP) model, with treatment, dialysis type and region as covariates.

Comparison groups

rhEPO v Daprodustat

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0351

Method

Chi-squared

Parameter type

Hazard ratio (HR)

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.01

Statistical analysis 2

Statistical analysis description

First Event Hazard ratio is presented using Model 2. Model 2 assumed treatment effect differs by number of events experienced. Hazard Ratio (HR) was estimated using a PWP model, with treatment, dialysis type and region as covariates.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3258

Method

Chi-squared

Parameter type

Hazard ratio (HR)

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.11

Statistical analysis 3

Statistical analysis description

Second Event Hazard ratio is presented using Model 2. Model 2 assumed treatment effect differs by number of events experienced. HR was estimated using a PWP model, with treatment, dialysis type and region as covariates.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0158

Method

Chi-squared

Parameter type

Hazard ratio (HR)

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.58

upper limit

0.98

Statistical analysis 4

Statistical analysis description

Third Event Hazard ratio is presented using Model 2. Model 2 assumed treatment effect differs by number of events experienced. HR was estimated using a PWP model, with treatment, dialysis type and region as covariates.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0981

Method

Chi-squared

Parameter type

Hazard ratio (HR)

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

1.17

Statistical analysis 5

Statistical analysis description

First Event Hazard ratio is presented using Model 3. Model 3 assumed treatment effect for first event differs from a common effect for subsequent events. HR was estimated using a PWP model, with treatment, dialysis type and region as covariates.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3258

Method

Chi-squared

Parameter type

Hazard ratio (HR)

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.11

Statistical analysis 6

Statistical analysis description

Subsequent Event Hazard ratio is presented using Model 3. Model 3 assumed treatment effect for first event differs from a common effect for subsequent events. HR was estimated using a PWP model, with treatment, dialysis type and region as covariates.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0058

Method

Chi-squared

Parameter type

Hazard ratio (HR)

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

0.94

Secondary: Time to First Occurrence of Adjudicated CV Mortality or Non-Fatal MI during CV events follow-up time period

Top of page

End point title

Time to First Occurrence of Adjudicated CV Mortality or Non-Fatal MI during CV events follow-up time period

End point description

Time to first occurrence of adjudicated CV mortality or non-fatal MI was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.

End point type

Secondary

End point timeframe

Up to 3.9 person-years for CV follow-up time period

End point values	Daprodustat	rhEPO
Number of subjects analysed	1487 ^[29]	1477 ^[30]
Units: Events per 100 person years
number (confidence interval 95%)	5.98 (5.18 to 6.86)	6.79 (5.94 to 7.73)

Notes
[29] - All Randomized (ITT) Population.
[30] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Hazard ratio was estimated using a Cox proportional hazard regression model with treatment group, dialysis type and region as covariates.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0872

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

1.06

Secondary: Time to First Occurrence of All-Cause Hospitalization during CV events follow-up time period

Top of page

End point title

Time to First Occurrence of All-Cause Hospitalization during CV events follow-up time period

End point description

All-cause hospitalization events were hospital admissions recorded on the Hospitalization electronic case report form (eCRF) with a hospitalization duration >=24 hours. Time to first occurrence of all-cause hospitalization was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.

End point type

Secondary

End point timeframe

Up to 3.9 person-years for CV follow-up time period

End point values	Daprodustat	rhEPO
Number of subjects analysed	1487 ^[31]	1477 ^[32]
Units: Events per 100 person years
number (confidence interval 95%)	43.92 (41.18 to 46.81)	46.03 (43.17 to 49.04)

Notes
[31] - All Randomized (ITT) Population.
[32] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Hazard ratio was estimated using a Cox proportional hazard regression model with treatment group, dialysis type and region as covariates.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.154

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.04

Secondary: Time to First Occurrence of All-Cause Hospital Re-admission within 30 Days during CV events follow-up time period

Top of page

End point title

Time to First Occurrence of All-Cause Hospital Re-admission within 30 Days during CV events follow-up time period

End point description

All-cause hospital re-admissions within 30days are defined as hospital admissions recorded on hospitalization eCRF with hospitalization duration of >=24 hours and admission date within 30days following previous discharge date of all-cause hospitalization event, where previous hospitalization was >=24 hours. Time to first occurrence of all-cause hospital re-admission within 30days was analyzed using Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date)+1. Incidence rate per 100person years calculated as(100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.

End point type

Secondary

End point timeframe

Up to 3.9 person-years for CV follow-up time period

End point values	Daprodustat	rhEPO
Number of subjects analysed	1487 ^[33]	1477 ^[34]
Units: Events per 100 person years
number (confidence interval 95%)	8.86 (7.85 to 9.95)	9.67 (8.62 to 10.82)

Notes
[33] - All Randomized (ITT) Population.
[34] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Hazard ratio was estimated using a Cox proportional hazard regression model with treatment group, dialysis type and region as covariates.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1244

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.07

Secondary: Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure or Thromboembolic events during CV events follow-up time period

Top of page

End point title

Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure or Thromboembolic events during CV events follow-up time period

End point description

Time to first occurrence of adjudicated MACE or hospitalization for heart failure or thromboembolic events were analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.

End point type

Secondary

End point timeframe

Up to 3.9 person-years for CV follow-up time period

End point values	Daprodustat	rhEPO
Number of subjects analysed	1487 ^[35]	1477 ^[36]
Units: Events per 100 person years
number (confidence interval 95%)	17.74 (16.28 to 19.30)	19.50 (17.94 to 21.16)

Notes
[35] - All Randomized (ITT) Population.
[36] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Hazard ratio was estimated using a Cox proportional hazard regression model with treatment group, dialysis type and region as covariates.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.054

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.02

Secondary: Time to First Occurrence of Adjudicated Hospitalization for Heart Failure during CV events follow-up time period

Top of page

End point title

Time to First Occurrence of Adjudicated Hospitalization for Heart Failure during CV events follow-up time period

End point description

Time to first occurrence of adjudicated hospitalization for heart failure was analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.

End point type

Secondary

End point timeframe

Up to 3.9 person-years for CV follow-up time period

End point values	Daprodustat	rhEPO
Number of subjects analysed	1487 ^[37]	1477 ^[38]
Units: Events per 100 person years
number (confidence interval 95%)	3.30 (2.72 to 3.97)	3.01 (2.45 to 3.65)

Notes
[37] - All Randomized (ITT) Population.
[38] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Hazard ratio was estimated using a Cox proportional hazard regression model with treatment group, dialysis type and region as covariates.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7658

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.45

Secondary: Time to First Occurrence of Adjudicated Thromboembolic Events during CV events follow-up time period

Top of page

End point title

Time to First Occurrence of Adjudicated Thromboembolic Events during CV events follow-up time period

End point description

Time to first occurrence of adjudicated thromboembolic events were analyzed using a Cox proportional hazards regression model with treatment group, dialysis type and region as covariates. Time to the first occurrence was computed as (event date minus randomization date) + 1. The incidence rate per 100 person years calculated as (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% CI. First event person years=(cumulative total time to first event for participants who have the event + cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.

End point type

Secondary

End point timeframe

Up to 3.9 person-years for CV follow-up time period

End point values	Daprodustat	rhEPO
Number of subjects analysed	1487 ^[39]	1477 ^[40]
Units: Events per 100 person years
number (confidence interval 95%)	5.66 (4.87 to 6.54)	6.75 (5.88 to 7.72)

Notes
[39] - All Randomized (ITT) Population.
[40] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Hazard ratio was estimated using a Cox proportional hazard regression model with treatment group, dialysis type and region as covariates.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0425

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

1.02

Secondary: Change From Baseline in Post-randomization Hemoglobin levels at Week 52

Top of page

End point title

Change From Baseline in Post-randomization Hemoglobin levels at Week 52

End point description

Blood samples were collected from participants for hemoglobin measurements. Change from Baseline was defined as post-Baseline value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using mixed model repeated measures (MMRM) model fitted from Baseline up to Week 52, excluding values collected during the stabilization period, with factors for treatment, time, dialysis type, region, Baseline hemoglobin and Baseline hemoglobin by time and treatment by time interactions. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1) and Week 52

End point values	Daprodustat	rhEPO
Number of subjects analysed	1358 ^[41]	1347 ^[42]
Units: Grams per deciliter
least squares mean (standard error)	0.26 ± 0.032	0.14 ± 0.032

Notes
[41] - All Randomized (ITT) Population.
[42] - All Randomized (ITT) Population.

Statistical analysis

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2705

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[43]

Method

Parameter type

LS mean difference

Point estimate

0.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.03

upper limit

0.21

Notes
[43] - Non-inferiority was to be established if the lower limit of the two-sided 95% CI for the treatment difference was greater than the pre-specified non-inferiority margin of -0.75 g/dL.

Secondary: Number of Hgb Responders in the Hgb Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52)

Top of page

End point title

Number of Hgb Responders in the Hgb Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52)

End point description

Mean Hgb during the evaluation period was defined as the mean of all evaluable Hgb values during the evaluation period (Week 28 to Week 52) including any evaluable unscheduled Hgb values that were taken during this time period. Hemoglobin responders were defined as participants with a mean Hgb during the evaluation period that falls within the Hgb analysis range of 10-11.5 g/dL. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Week 28 to Week 52

End point values	Daprodustat	rhEPO
Number of subjects analysed	1238 ^[44]	1247 ^[45]
Units: Participants	903	866

Notes
[44] - All Randomized (ITT) Population.
[45] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Cochran-Mantel-Haenszel (CMH) test adjusted for dialysis type, and region was used to compare the number of responders between the treatment groups.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2485

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0367

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in response rate

Point estimate

3.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

7.1

Secondary: Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Non-inferiority analysis

Top of page

End point title

Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Non-inferiority analysis

End point description

Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the evaluation period (Week 28 to Week 52), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during evaluation period is calculated as time in range during the evaluation period / [Earlier of (Date of the last evaluable Hgb value, Week 52 visit date) – Later of (Date of the first evaluable Hgb value that between Week 16 and Week 52 inclusive, Week 28 visit date)]. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Week 28 to Week 52

End point values	Daprodustat	rhEPO
Number of subjects analysed	1202 ^[46]	1224 ^[47]
Units: Percentage of days
median (full range (min-max))	60.9 (0.0 to 100.0)	59.4 (0.0 to 100.0)

Notes
[46] - All Randomized (ITT) Population.
[47] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Hodges-Lehmann estimate of the treatment difference (daprodustat-rhEPO) and associated two-sided asymptotic 95% CI is presented.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2426

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[48]

Method

Parameter type

Median difference (final values)

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

3.86

Notes
[48] - Non-inferiority was to be established if the lower limit of the two-sided 95% confidence interval for the treatment difference was greater than non-inferiority margin of -15%.

Secondary: Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Superiority analysis

Top of page

End point title

Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Superiority analysis

End point description

End point type

Secondary

End point timeframe

Week 28 to Week 52

End point values	Daprodustat	rhEPO
Number of subjects analysed	1202 ^[49]	1224 ^[50]
Units: Percentage of days
median (full range (min-max))	60.9 (0.0 to 100.0)	59.4 (0.0 to 100.0)

Notes
[49] - All Randomized (ITT) Population.
[50] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Mann-Whitney estimate (Probability) of the treatment effect has been presented.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2426

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0805

Method

van Elteren test

Parameter type

Probability

Point estimate

0.52

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

0.54

Secondary: Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of study): Non-inferiority analysis

Top of page

End point title

Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of study): Non-inferiority analysis

End point description

Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the maintenance period (Week 28 to end of study), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time in the analysis range during maintenance period is calculated as time in range during the maintenance period / [Earlier of (Date of the last evaluable Hgb value, End of study date)– Later of (Date of the first evaluable Hgb value that is on or after week 16, Week 28 visit date)]. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Week 28 to end of study (3.9 person-years for follow-up time period)

End point values	Daprodustat	rhEPO
Number of subjects analysed	1203 ^[51]	1224 ^[52]
Units: Percentage of days
median (full range (min-max))	60.9 (0.0 to 100.0)	57.7 (0.0 to 100.0)

Notes
[51] - All Randomized (ITT) Population.
[52] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Hodges-Lehmann estimate of the treatment difference (daprodustat-rhEPO) and associated two-sided asymptotic 95% CI is presented.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2427

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[53]

Method

Parameter type

Median difference (final values)

Point estimate

2.18

Confidence interval

level

95%

sides

2-sided

lower limit

0.28

upper limit

4.05

Notes
[53] - Non-inferiority was to be established if the lower limit of the two-sided 95% confidence interval for the treatment difference was greater than non-inferiority margin of -15%.

Secondary: Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of study): Superiority analysis

Top of page

End point title

Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of study): Superiority analysis

End point description

End point type

Secondary

End point timeframe

Week 28 to end of study (3.9 person-years for follow-up time period)

End point values	Daprodustat	rhEPO
Number of subjects analysed	1203 ^[54]	1224 ^[55]
Units: Percentage of days
median (full range (min-max))	60.9 (0.0 to 100.0)	57.7 (0.0 to 100.0)

Notes
[54] - All Randomized (ITT) Population.
[55] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Mann-Whitney estimate (Probability) of the treatment effect has been presented.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2427

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0139

Method

van Elteren test

Parameter type

Probability

Point estimate

0.53

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

0.55

Secondary: Change from Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52

Top of page

End point title

Change from Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52

End point description

SBP, DBP and MAP were measured in a semi-supine or seated position in the dialysis chair after at least a 5-minutes of rest. MAP is the average BP in an individual's arteries during a single cardiac cycle. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using MMRM model with treatment group + time + dialysis type + region + Baseline value + Baseline value*time + treatment group*time, using an unstructured covariance matrix. Data for post-dialysis BP measurements have been presented. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Week -4) and Week 52

End point values	Daprodustat	rhEPO
Number of subjects analysed	1455 ^[56]	1442 ^[57]
Units: Millimeter of mercury
least squares mean (standard error)
SBP	-0.61 ± 0.582	-0.93 ± 0.578
DBP	-1.04 ± 0.326	-0.58 ± 0.324
MAP	-0.89 ± 0.370	-0.71 ± 0.368

Notes
[56] - All Randomized (ITT) Population.
[57] - All Randomized (ITT) Population.

Statistical analysis 1

Statistical analysis description

The difference in change from Baseline in SBP at Week 52 was analyzed with a MMRM approach with an unstructured covariance matrix to compare the difference in means between arms.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2897

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6551

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.33

Confidence interval

level

95%

sides

2-sided

lower limit

-1.28

upper limit

1.94

Statistical analysis 2

Statistical analysis description

The difference in change from Baseline in DBP at Week 52 was analyzed with a MMRM approach with an unstructured covariance matrix to compare the difference in means between arms.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2897

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1586

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.46

Confidence interval

level

95%

sides

2-sided

lower limit

-1.36

upper limit

0.44

Statistical analysis 3

Statistical analysis description

The difference in change from Baseline in MAP at Week 52 was analyzed with a MMRM approach with an unstructured covariance matrix to compare the difference in means between arms.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2897

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3646

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.18

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

0.84

Secondary: Change from Baseline in SBP, DBP, MAP at End of Treatment

Top of page

End point title

Change from Baseline in SBP, DBP, MAP at End of Treatment

End point description

SBP, DBP and MAP were measured in a semi-supine or seated position in the dialysis chair after at least a 5-minutes of rest. MAP is an average BP in an individual's arteries during a single cardiac cycle. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. This analysis was carried out by using ANCOVA model with terms for treatment group, dialysis type, region and Baseline value. Data for post-dialysis BP measurements have been presented. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Week -4) and 45.1 months

End point values	Daprodustat	rhEPO
Number of subjects analysed	1468 ^[58]	1454 ^[59]
Units: Millimeter of mercury
least squares mean (standard error)
SBP	-0.43 ± 0.554	-0.43 ± 0.557
DBP	-0.92 ± 0.310	-1.37 ± 0.312
MAP	-0.75 ± 0.350	-1.06 ± 0.351

Notes
[58] - All Randomized (ITT) Population.
[59] - All Randomized (ITT) Population.

Statistical analysis 1

Statistical analysis description

For SBP: Treatment group comparisons were based on an ANCOVA model with terms for treatment group, dialysis type, region and Baseline value.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2922

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5012

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.54

upper limit

1.54

Statistical analysis 2

Statistical analysis description

For DBP: Treatment group comparisons were based on an ANCOVA model with terms for treatment group, dialysis type, region and Baseline value.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2922

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8451

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

0.45

Confidence interval

level

95%

sides

2-sided

lower limit

-0.42

upper limit

1.31

Statistical analysis 3

Statistical analysis description

For MAP: Treatment group comparisons were based on an ANCOVA model with terms for treatment group, dialysis type, region and Baseline value.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2922

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7312

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

0.31

Confidence interval

level

95%

sides

2-sided

lower limit

-0.67

upper limit

1.28

Secondary: Blood Pressure (BP) Exacerbation Event Rate per 100 Participant Years

Top of page

End point title

Blood Pressure (BP) Exacerbation Event Rate per 100 Participant Years

End point description

BP exacerbation was defined (based on post-dialysis) as: SBP >= 25 millimeter of mercury (mmHg) increased from Baseline or SBP >=180 mmHg; DBP >=15 mmHg increased from Baseline or DBP >=110 mmHg. The BP exacerbation events per 100 participant years was estimated using the negative binomial model with treatment, dialysis type and region as covariates and the logarithm of time on-treatment as an offset variable. Data for post-dialysis BP measurements have been presented. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Day 1 to end of study (3.9 person-years for follow-up time period)

End point values	Daprodustat	rhEPO
Number of subjects analysed	1470 ^[60]	1458 ^[61]
Units: Events per 100 participant years
number (confidence interval 95%)	207.13 (188.83 to 227.21)	206.38 (187.88 to 226.71)

Notes
[60] - All Randomized (ITT) Population.
[61] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Ratio of model estimated exacerbation rates and CIs were estimated using a negative binomial model for the treatment group comparison.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2928

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.529

Method

Negative binomial model

Parameter type

Ratio of exacerbation rate

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.91

upper limit

1.11

Secondary: Number of Participants with at Least one BP Exacerbation Event During Study

Top of page

End point title

Number of Participants with at Least one BP Exacerbation Event During Study

End point description

BP exacerbation was defined as: SBP >= 25 mmHg increased from Baseline or SBP >=180 mmHg; DBP >=15 mmHg increased from Baseline or DBP >=110 mmHg. Number of participants with at least one BP exacerbation event is presented. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Day 1 to end of study (3.9 person-years for follow-up time period)

End point values	Daprodustat	rhEPO
Number of subjects analysed	1480 ^[62]	1470 ^[63]
Units: Participants	1191	1186

Notes
[62] - All Randomized (ITT) Population.
[63] - All Randomized (ITT) Population.

No statistical analyses for this end point

Secondary: Percentage of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria

Top of page

End point title

Percentage of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria

End point description

Percentage of participants permanently stopping randomized treatment due to meeting rescue criteria has been presented.

End point type

Secondary

End point timeframe

Day 1 to 45.1 months

End point values	Daprodustat	rhEPO
Number of subjects analysed	1487 ^[64]	1477 ^[65]
Units: Percentage of participants
number (not applicable)	3.6	3.6

Notes
[64] - All Randomized (ITT) Population.
[65] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

Hazard ratio was estimated using a Cox proportional hazard regression model adjusted for treatment group, dialysis type and region.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2964

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5772

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.52

Secondary: Change from Baseline in On-Treatment Physical Component Score (PCS) using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52

Top of page

End point title

Change from Baseline in On-Treatment Physical Component Score (PCS) using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52

End point description

SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant’s level of performance in following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). The PCS is an average score derived from 4 domains (physical functioning, role-physical, bodily pain and general health) representing overall physical health. PCS ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52

End point values	Daprodustat	rhEPO
Number of subjects analysed	990 ^[66]	943 ^[67]
Units: Scores on a scale
least squares mean (standard error)
Week 8, n=982,936	0.30 ± 0.205	0.01 ± 0.210
Week 12, n=990,943	0.33 ± 0.203	-0.27 ± 0.207
Week 28, n=836,819	-0.23 ± 0.229	-0.57 ± 0.232
Week 52, n=729,707	-0.52 ± 0.248	-1.05 ± 0.252

Notes
[66] - All Randomized (ITT) Population.
[67] - All Randomized (ITT) Population.

Statistical analysis 1

Statistical analysis description

Week 8: Model was fitted from Baseline up to Week 52 and the model adjusted Week 8 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.162

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-0.29

upper limit

0.86

Statistical analysis 2

Statistical analysis description

Week 12: Model was fitted from Baseline up to Week 52 and the model adjusted Week 12 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.018

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.04

upper limit

1.18

Statistical analysis 3

Statistical analysis description

Week 28: Model was fitted from Baseline up to Week 52 and the model adjusted Week 28 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.153

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.33

Confidence interval

level

95%

sides

2-sided

lower limit

-0.31

upper limit

0.97

Statistical analysis 4

Statistical analysis description

Week 52: Model was fitted from Baseline up to Week 52 and the model adjusted Week 52 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0686

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.53

Confidence interval

level

95%

sides

2-sided

lower limit

-0.17

upper limit

1.22

Secondary: Change from Baseline in On-Treatment Mental Component Score (MCS) using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

Top of page

End point title

Change from Baseline in On-Treatment Mental Component Score (MCS) using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

End point description

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant’s level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). MCS is an average score derived from 4 domains (vitality, social functioning, role-emotional and mental health) representing overall mental health. MCS ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52

End point values	Daprodustat	rhEPO
Number of subjects analysed	990 ^[68]	943 ^[69]
Units: Scores on a scale
least squares mean (standard error)
Week 8, n=982,936	-0.38 ± 0.254	-0.21 ± 0.260
Week 12, n=990,943	-0.55 ± 0.262	-0.72 ± 0.268
Week 28, n=836,819	-1.25 ± 0.286	-1.23 ± 0.290
Week 52, n=729,707	-1.63 ± 0.311	-1.03 ± 0.316

Notes
[68] - All Randomized (ITT) Population.
[69] - All Randomized (ITT) Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6807

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.88

upper limit

0.54

Statistical analysis 2

Statistical analysis description

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3256

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.57

upper limit

0.91

Statistical analysis 3

Statistical analysis description

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5144

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.81

upper limit

0.78

Statistical analysis 4

Statistical analysis description

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.912

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.47

upper limit

0.27

Secondary: Change from Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52

Top of page

End point title

Change from Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52

End point description

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant’s level of performance in the following 8 health domains: bodily pain, general health, mental health, role-emotional (role limitations caused by emotional problems), role-physical (role limitations caused by physical problems), social functioning (Social fun), physical functioning (Phy. fun) and vitality. Each domain is scored from 0 (poorer health) to 100 (better health). Each domain score ranges from 0 to 100, higher score indicates a better health state and better functioning. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52

End point values	Daprodustat	rhEPO
Number of subjects analysed	990 ^[70]	943 ^[71]
Units: Scores on a scale
least squares mean (standard error)
Bodily pain: Week 8, n=982,936	-0.13 ± 0.265	0.12 ± 0.272
Bodily pain: Week 12, n=990,943	0.20 ± 0.267	-0.39 ± 0.274
Bodily pain: Week 28, n=836,819	-0.70 ± 0.297	-0.74 ± 0.301
Bodily pain: Week 52, n=729,707	-1.12 ± 0.313	-1.39 ± 0.318
General health: Week 8, n=982,936	-0.39 ± 0.208	-0.65 ± 0.213
General health: Week 12, n=990,943	-0.59 ± 0.210	-1.04 ± 0.215
General health: Week 28, n=836,819	-1.32 ± 0.232	-0.99 ± 0.235
General health: Week 52, n=729,707	-1.51 ± 0.251	-1.22 ± 0.255
Mental health: Week 8, n=982,936	-0.43 ± 0.238	-0.47 ± 0.244
Mental health: Week 12, n=990,943	-0.86 ± 0.247	-0.81 ± 0.253
Mental health: Week 28, n=836,819	-1.30 ± 0.267	-1.43 ± 0.270
Mental health: Week 52, n=729,707	-1.97 ± 0.296	-1.16 ± 0.301
Role-emotional: Week 8, n=982,936	-0.10 ± 0.310	-0.02 ± 0.317
Role-emotional: Week 12, n=990,943	-0.17 ± 0.311	-0.53 ± 0.318
Role-emotional: Week 28, n=836,819	-0.95 ± 0.335	-0.90 ± 0.339
Role-emotional: Week 52, n=729,707	-0.83 ± 0.358	-0.92 ± 0.363
Role-physical: Week 8, n=982,936	0.40 ± 0.241	0.32 ± 0.246
Role-physical: Week 12, n=990,943	0.48 ± 0.239	0.08 ± 0.245
Role-physical: Week 28, n=836,819	-0.10 ± 0.257	-0.39 ± 0.260
Role-physical: Week 52, n=729,707	-0.21 ± 0.285	-0.60 ± 0.289
Social functioning: Week 8, n=982,936	0.24 ± 0.241	0.38 ± 0.247
Social functioning: Week 12, n=990,943	0.25 ± 0.255	-0.44 ± 0.261
Social functioning: Week 28, n=836,819	-0.61 ± 0.280	-0.94 ± 0.283
Social functioning: Week 52, n=729,707	-1.12 ± 0.315	-1.14 ± 0.320

Notes
[70] - All Randomized (ITT) Population.
[71] - All Randomized (ITT) Population.

Statistical analysis 1

Statistical analysis description

Bodily pain,Week8: Model was fitted from Baseline up to Week52 and model adjusted Week8 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7432

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-0.99

upper limit

0.5

Statistical analysis 2

Statistical analysis description

Bodily pain,Week12: Model was fitted from Baseline up to Week52 and model adjusted Week12 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0631

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.58

Confidence interval

level

95%

sides

2-sided

lower limit

-0.16

upper limit

1.33

Statistical analysis 3

Statistical analysis description

Bodily pain,Week28: Model was fitted from Baseline up to Week52 and model adjusted Week28 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4604

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.79

upper limit

0.87

Statistical analysis 4

Statistical analysis description

Bodily pain,Week52: Model was fitted from Baseline up to Week52 and model adjusted Week52 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2688

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.28

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

1.15

Statistical analysis 5

Statistical analysis description

General health,Week8:Model was fitted from Baseline up to Week52 and model adjusted Week8 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1918

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.26

Confidence interval

level

95%

sides

2-sided

lower limit

-0.32

upper limit

0.84

Statistical analysis 6

Statistical analysis description

General health,Week12:Model was fitted from Baseline up to Week52 and model adjusted Week12 data has been presented, with factors for treatment, time, dialysis type, region,Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0677

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.45

Confidence interval

level

95%

sides

2-sided

lower limit

-0.14

upper limit

1.04

Statistical analysis 7

Statistical analysis description

General health,Week28:Model was fitted from Baseline up to Week52 and model adjusted Week28 data has been presented, with factors for treatment, time, dialysis type, region,Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8386

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.33

Confidence interval

level

95%

sides

2-sided

lower limit

-0.98

upper limit

0.32

Statistical analysis 8

Statistical analysis description

General health,Week52:Model was fitted from Baseline up to Week52 and model adjusted Week52 data has been presented, with factors for treatment, time, dialysis type, region,Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7928

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-0.99

upper limit

0.41

Statistical analysis 9

Statistical analysis description

Mental health,Week8:Model was fitted from Baseline up to Week52 and model adjusted Week8 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4537

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.63

upper limit

0.71

Statistical analysis 10

Statistical analysis description

Mental health,Week12:Model was fitted from Baseline up to Week52 and model adjusted Week12 data has been presented, with factors for treatment, time, dialysis type, region,Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5548

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.74

upper limit

0.65

Statistical analysis 11

Statistical analysis description

Mental health,Week28:Model was fitted from Baseline up to Week52 and model adjusted Week28 data has been presented, with factors for treatment, time, dialysis type, region,Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3626

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.13

Confidence interval

level

95%

sides

2-sided

lower limit

-0.61

upper limit

0.88

Statistical analysis 12

Statistical analysis description

Mental health,Week52:Model was fitted from Baseline up to Week52 and model adjusted Week52 data has been presented, with factors for treatment, time, dialysis type, region,Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9721

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.81

Confidence interval

level

95%

sides

2-sided

lower limit

-1.64

upper limit

0.02

Statistical analysis 13

Statistical analysis description

Role-emotional,Week8:Model was fitted from Baseline up to Week52 and model adjusted Week8 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5789

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.96

upper limit

0.78

Statistical analysis 14

Statistical analysis description

Role-emotional,Week12:Model was fitted from Baseline up to Week52 and model adjusted Week12 data has been presented, with factors for treatment, time, dialysis type, region,Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2054

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.37

Confidence interval

level

95%

sides

2-sided

lower limit

-0.51

upper limit

1.24

Statistical analysis 15

Statistical analysis description

Role-emotional,Week28:Model was fitted from Baseline up to Week52 and model adjusted Week28 data has been presented, with factors for treatment, time, dialysis type, region,Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5389

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.98

upper limit

0.89

Statistical analysis 16

Statistical analysis description

Role-emotional,Week52:Model was fitted from Baseline up to Week52 and model adjusted Week52 data has been presented, with factors for treatment, time, dialysis type, region,Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4289

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.91

upper limit

1.09

Statistical analysis 17

Statistical analysis description

Role-physical,Week8:Model was fitted from Baseline up to Week52 and model adjusted Week8 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4096

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

0.75

Statistical analysis 18

Statistical analysis description

Role-physical,Week12:Model was fitted from Baseline up to Week52 and model adjusted Week12 data has been presented, with factors for treatment, time, dialysis type, region,Baseline value and Baseline value by time and treatment by time interactions

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1196

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.27

upper limit

1.07

Statistical analysis 19

Statistical analysis description

Role-physical,Week28:Model was fitted from Baseline up to Week52 and model adjusted Week28 data has been presented, with factors for treatment, time, dialysis type, region,Baseline value and Baseline value by time and treatment by time interactions

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2093

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.42

upper limit

1.01

Statistical analysis 20

Statistical analysis description

Role-physical,Week52:Model was fitted from Baseline up to Week52 and model adjusted Week52 data has been presented, with factors for treatment, time, dialysis type, region,Baseline value and Baseline value by time and treatment by time interactions

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1674

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

1.19

Statistical analysis 21

Statistical analysis description

Social fun, Week 8: Model was fitted from Baseline up to Week52 and model adjusted Week8 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6585

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.14

Confidence interval

level

95%

sides

2-sided

lower limit

-0.82

upper limit

0.54

Statistical analysis 22

Statistical analysis description

Social fun, Week 12: Model was fitted from Baseline up to Week52 and model adjusted Week12 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0293

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

-0.03

upper limit

1.4

Statistical analysis 23

Statistical analysis description

Social fun, Week 28: Model was fitted from Baseline up to Week52 and model adjusted Week28 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2057

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.33

Confidence interval

level

95%

sides

2-sided

lower limit

-0.45

upper limit

1.11

Statistical analysis 24

Statistical analysis description

Social fun, Week 52: Model was fitted from Baseline up to Week52 and model adjusted Week52 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4849

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.86

upper limit

0.9

Secondary: Change from Baseline in On-Treatment Vitality scores using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

Top of page

End point title

Change from Baseline in On-Treatment Vitality scores using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

End point description

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant’s level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). Vitality score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52

End point values	Daprodustat	rhEPO
Number of subjects analysed	990 ^[72]	943 ^[73]
Units: Scores on a scale
least squares mean (standard error)
Week 8, n=982,936	-0.23 ± 0.219	-0.26 ± 0.224
Week 12, n=990,943	-0.17 ± 0.227	-0.51 ± 0.232
Week 28, n=836,819	-0.79 ± 0.242	-1.03 ± 0.245
Week 52, n=729,707	-1.19 ± 0.268	-1.04 ± 0.272

Notes
[72] - All Randomized (ITT) Population.
[73] - All Randomized (ITT) Population.

Statistical analysis 1

Statistical analysis description

Week 8: Model was fitted from Baseline up to Week 52 and model adjusted Week 8 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4621

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.58

upper limit

0.64

Statistical analysis 2

Statistical analysis description

Week 12: Model was fitted from Baseline up to Week 52 and model adjusted Week 12 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1439

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.35

Confidence interval

level

95%

sides

2-sided

lower limit

-0.29

upper limit

0.98

Statistical analysis 3

Statistical analysis description

Week 28: Model was fitted from Baseline up to Week 52 and model adjusted Week 28 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2392

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.24

Confidence interval

level

95%

sides

2-sided

lower limit

-0.43

upper limit

0.92

Statistical analysis 4

Statistical analysis description

Week 52: Model was fitted from Baseline up to Week 52 and model adjusted Week 52 data has been presented, with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6545

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.15

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

0.6

Secondary: Change from Baseline in On-Treatment Physical Functioning domain scores using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

Top of page

End point title

Change from Baseline in On-Treatment Physical Functioning domain scores using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

End point description

The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant’s level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). Physical functioning score ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as on-treatment visit value minus (-) Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52

End point values	Daprodustat	rhEPO
Number of subjects analysed	990 ^[74]	943 ^[75]
Units: Scores on a scale
least squares mean (standard error)
Week 8, n=982,936	0.48 ± 0.237	-0.16 ± 0.243
Week 12, n=990,943	0.11 ± 0.240	-0.45 ± 0.246
Week 28, n=836,819	-0.20 ± 0.273	-0.97 ± 0.277
Week 52, n=729,707	-0.61 ± 0.291	-1.19 ± 0.296

Notes
[74] - All Randomized (ITT) Population.
[75] - All Randomized (ITT) Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.029

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

-0.02

upper limit

1.31

Statistical analysis 2

Statistical analysis description

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0509

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.56

Confidence interval

level

95%

sides

2-sided

lower limit

-0.11

upper limit

1.24

Statistical analysis 3

Statistical analysis description

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0237

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.01

upper limit

1.53

Statistical analysis 4

Statistical analysis description

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

1933

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0828

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.58

Confidence interval

level

95%

sides

2-sided

lower limit

-0.24

upper limit

1.39

Secondary: Change from Baseline in On-Treatment Health Utility EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Questionnaire Score at Week 52

Top of page

End point title

Change from Baseline in On-Treatment Health Utility EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Questionnaire Score at Week 52

End point description

EQ-5D-5L is self-assessment questionnaire,consisting of 5 items covering 5 dimensions (mobility,self care,usual activities,pain/discomfort and anxiety/depression). Each dimension is measured by 5-point Likert scale (1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Each of these 5 figure health states were converted to a single index score by applying country-specific value set formula that attaches weights to dimensions and levels. Range for EQ-5D-5L index score is -0.594 (worst health) to 1 (full health state). Change from Baseline was calculated as on-treatment visit value-Baseline value. Baseline was latest non-missing pre-dose assessment on or before randomization date. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1) and Week 52

End point values	Daprodustat	rhEPO
Number of subjects analysed	333 ^[76]	329 ^[77]
Units: Scores on a scale
least squares mean (standard error)	-0.0198 ± 0.01179	-0.0201 ± 0.01187

Notes
[76] - All Randomized (ITT) Population.
[77] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

MMRM model was fitted from Baseline up to Week 52 with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

662

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4939

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.0003

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0326

upper limit

0.0331

Secondary: Change from Baseline in On-Treatment EuroQol Visual Analogue Scale (EQ-VAS) at Week 52

Top of page

End point title

Change from Baseline in On-Treatment EuroQol Visual Analogue Scale (EQ-VAS) at Week 52

End point description

The EQ VAS records the respondent’s self-rated health on a vertical VAS, ranging from 0 to 100, where 0 represents the worst health one can imagine and 100 represents the best health one can imagine. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1) and Week 52

End point values	Daprodustat	rhEPO
Number of subjects analysed	333 ^[78]	329 ^[79]
Units: Scores on a scale
least squares mean (standard error)	-1.0 ± 0.86	0.8 ± 0.87

Notes
[78] - All Randomized (ITT) Population.
[79] - All Randomized (ITT) Population.

Statistical analysis

Statistical analysis description

MMRM model was fitted from Baseline up to Week 52 with factors for treatment, time, dialysis type, region, Baseline value and Baseline value by time and treatment by time interactions.

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

662

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9292

Method

MMRM

Parameter type

LS mean difference

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.2

upper limit

0.6

Secondary: Change from Baseline in On-Treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52

Top of page

End point title

Change from Baseline in On-Treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52

End point description

The PGI-S is a 1-item questionnaire designed to assess participant’s impression of disease severity on a 5-point disease severity scale (0=absent, 1=mild, 2=moderate, 3=severe, or 4=very severe). A higher score indicated worse outcome. Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1), Weeks 8, 12, 28 and 52

End point values	Daprodustat	rhEPO
Number of subjects analysed	1102 ^[80]	1073 ^[81]
Units: Scores on a scale
least squares mean (standard error)
Week 8, n=1102,1064	-0.03 ± 0.024	0.02 ± 0.025
Week 12, n=1102,1073	0.02 ± 0.025	0.06 ± 0.025
Week 28, n=934,933	0.04 ± 0.027	0.08 ± 0.027
Week 52, n=826,814	0.06 ± 0.029	0.11 ± 0.030

Notes
[80] - All Randomized (ITT) Population.
[81] - All Randomized (ITT) Population.

Statistical analysis 1

Statistical analysis description

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2175

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0428

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.13

upper limit

0.01

Statistical analysis 2

Statistical analysis description

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2175

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1155

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.11

upper limit

0.03

Statistical analysis 3

Statistical analysis description

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2175

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1426

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.12

upper limit

0.03

Statistical analysis 4

Statistical analysis description

Comparison groups

Daprodustat v rhEPO

Number of subjects included in analysis

2175

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1152

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.13

upper limit

0.03

Adverse events

Top of page

Timeframe for reporting adverse events

All-cause mortality, treatment emergent serious adverse events (TESAEs) and non-serious treatment emergent adverse events (TEAEs) were collected up to 3.9 person-years for CV follow-up time period

Adverse event reporting additional description

All-cause mortality used All Randomized (ITT) Population, which comprised of all randomized participants and treatment to which the participant was randomized. TESAEs and non-serious TEAEs used the Safety Population, which included all randomized participants who received at least 1 dose of randomized treatment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.0

Reporting group title

rhEPO

Reporting group description

Reporting group title

Daprodustat

Reporting group description

Serious adverse events	rhEPO	Daprodustat
Total subjects affected by serious adverse events
subjects affected / exposed	748 / 1474 (50.75%)	773 / 1482 (52.16%)
number of deaths (all causes)	300	294
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer
subjects affected / exposed	2 / 1474 (0.14%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 2	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Basal cell carcinoma
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bladder cancer
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Hepatic cancer
subjects affected / exposed	3 / 1474 (0.20%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0
Parathyroid tumour benign
subjects affected / exposed	0 / 1474 (0.00%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Renal neoplasm
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1
Breast cancer
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Colon adenoma
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Colon cancer
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Papillary renal cell carcinoma
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Papillary thyroid cancer
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Plasma cell myeloma
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal cell carcinoma
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Squamous cell carcinoma of skin
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Transitional cell carcinoma
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1
Thyroid adenoma
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Uterine leiomyoma
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Acute myeloid leukaemia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Adenocarcinoma gastric
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Adenocarcinoma of colon
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Adrenal adenoma
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
B-cell type acute leukaemia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Benign neoplasm of ampulla of Vater
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Benign renal neoplasm
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bile duct cancer
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Bladder cancer stage 0, with cancer in situ
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bladder papilloma
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bladder transitional cell carcinoma
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Bone neoplasm
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Breast cancer stage II
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Carcinoid tumour pulmonary
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Carcinoma in situ of eye
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac valve fibroelastoma
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colon cancer metastatic
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Endometrial adenocarcinoma
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
External ear neoplasm malignant
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Inflammatory pseudotumour
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lung cancer metastatic
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Lung adenocarcinoma
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Malignant melanoma
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Meningioma
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metastatic neoplasm
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Metastases to lung
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metastases to bone
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ovarian cancer
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ovarian cancer metastatic
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Pancreatic carcinoma
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Papilloma
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Prostate cancer metastatic
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal adenocarcinoma
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Refractory cytopenia with unilineage dysplasia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal cell carcinoma stage I
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Salivary gland cancer
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Squamous cell carcinoma
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Squamous cell carcinoma of lung
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract neoplasm
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ureteric cancer regional
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Hypertension
subjects affected / exposed	11 / 1474 (0.75%)	16 / 1482 (1.08%)
occurrences causally related to treatment / all	0 / 14	1 / 18
deaths causally related to treatment / all	0 / 0	1 / 1
Hypotension
subjects affected / exposed	19 / 1474 (1.29%)	5 / 1482 (0.34%)
occurrences causally related to treatment / all	0 / 19	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral ischaemia
subjects affected / exposed	7 / 1474 (0.47%)	12 / 1482 (0.81%)
occurrences causally related to treatment / all	0 / 7	0 / 14
deaths causally related to treatment / all	0 / 0	0 / 1
Hypertensive urgency
subjects affected / exposed	8 / 1474 (0.54%)	6 / 1482 (0.40%)
occurrences causally related to treatment / all	2 / 10	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral arterial occlusive disease
subjects affected / exposed	6 / 1474 (0.41%)	6 / 1482 (0.40%)
occurrences causally related to treatment / all	0 / 6	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Dialysis hypotension
subjects affected / exposed	5 / 1474 (0.34%)	6 / 1482 (0.40%)
occurrences causally related to treatment / all	0 / 5	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Hypertensive emergency
subjects affected / exposed	8 / 1474 (0.54%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 8	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Extremity necrosis
subjects affected / exposed	7 / 1474 (0.47%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 9	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 0
Haematoma
subjects affected / exposed	5 / 1474 (0.34%)	5 / 1482 (0.34%)
occurrences causally related to treatment / all	0 / 6	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Aortic stenosis
subjects affected / exposed	7 / 1474 (0.47%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 9	0 / 2
deaths causally related to treatment / all	0 / 2	0 / 0
Hypertensive crisis
subjects affected / exposed	4 / 1474 (0.27%)	5 / 1482 (0.34%)
occurrences causally related to treatment / all	0 / 5	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Orthostatic hypotension
subjects affected / exposed	3 / 1474 (0.20%)	5 / 1482 (0.34%)
occurrences causally related to treatment / all	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Accelerated hypertension
subjects affected / exposed	5 / 1474 (0.34%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 6	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Brachiocephalic vein stenosis
subjects affected / exposed	2 / 1474 (0.14%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral vascular disorder
subjects affected / exposed	1 / 1474 (0.07%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Subclavian vein stenosis
subjects affected / exposed	2 / 1474 (0.14%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 2	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	1 / 1474 (0.07%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Dry gangrene
subjects affected / exposed	1 / 1474 (0.07%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Hypovolaemic shock
subjects affected / exposed	1 / 1474 (0.07%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhage
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral artery occlusion
subjects affected / exposed	3 / 1474 (0.20%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Shock haemorrhagic
subjects affected / exposed	0 / 1474 (0.00%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1
Steal syndrome
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Arterial haemorrhage
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Jugular vein thrombosis
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vena cava thrombosis
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Venous stenosis
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 5	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Venous thrombosis limb
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Aortic dissection
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Arterial disorder
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Arterial occlusive disease
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Circulatory collapse
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic microangiopathy
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic vascular disorder
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Granulomatosis with polyangiitis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ischaemic limb pain
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral artery thrombosis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral vein occlusion
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral artery stenosis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Shock
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Subclavian vein thrombosis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Superior vena cava occlusion
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Superior vena cava syndrome
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombophlebitis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombosis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Venous thrombosis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Non-cardiac chest pain
subjects affected / exposed	16 / 1474 (1.09%)	10 / 1482 (0.67%)
occurrences causally related to treatment / all	0 / 23	1 / 11
deaths causally related to treatment / all	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	8 / 1474 (0.54%)	7 / 1482 (0.47%)
occurrences causally related to treatment / all	0 / 8	0 / 7
deaths causally related to treatment / all	0 / 1	0 / 0
Asthenia
subjects affected / exposed	6 / 1474 (0.41%)	5 / 1482 (0.34%)
occurrences causally related to treatment / all	0 / 6	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 1
Death
subjects affected / exposed	2 / 1474 (0.14%)	9 / 1482 (0.61%)
occurrences causally related to treatment / all	0 / 2	0 / 9
deaths causally related to treatment / all	0 / 2	0 / 9
Chest pain
subjects affected / exposed	5 / 1474 (0.34%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 5	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Oedema peripheral
subjects affected / exposed	4 / 1474 (0.27%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Sudden death
subjects affected / exposed	1 / 1474 (0.07%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 1	0 / 3
Sudden cardiac death
subjects affected / exposed	1 / 1474 (0.07%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 1	0 / 3
Fatigue
subjects affected / exposed	3 / 1474 (0.20%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Impaired healing
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Catheter site haemorrhage
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Complication associated with device
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Device related thrombosis
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Generalised oedema
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Multiple organ dysfunction syndrome
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 1
Peripheral swelling
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Systemic inflammatory response syndrome
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular stent stenosis
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Catheter site oedema
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Catheter site thrombosis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Chest discomfort
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cyst
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Drug withdrawal syndrome
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gait disturbance
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Mucosal inflammation
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Oedema
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Serositis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Swelling face
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ulcer haemorrhage
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ulcer
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular stent thrombosis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Immune system disorders
Anaphylactic reaction
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Amyloidosis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypersensitivity
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Kidney transplant rejection
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal transplant failure
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Social circumstances
Loss of personal independence in daily activities
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Prostatitis
subjects affected / exposed	2 / 1474 (0.14%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Endometriosis
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Menorrhagia
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ovarian cyst
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Acquired hydrocele
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Adenomyosis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Benign prostatic hyperplasia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ovarian disorder
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Postmenopausal haemorrhage
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Scrotal oedema
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Testicular infarction
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Uterine haemorrhage
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	13 / 1474 (0.88%)	14 / 1482 (0.94%)
occurrences causally related to treatment / all	0 / 14	0 / 16
deaths causally related to treatment / all	0 / 0	0 / 1
Pulmonary oedema
subjects affected / exposed	15 / 1474 (1.02%)	11 / 1482 (0.74%)
occurrences causally related to treatment / all	0 / 17	0 / 14
deaths causally related to treatment / all	0 / 0	0 / 0
Acute pulmonary oedema
subjects affected / exposed	15 / 1474 (1.02%)	10 / 1482 (0.67%)
occurrences causally related to treatment / all	0 / 16	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 1
Dyspnoea
subjects affected / exposed	12 / 1474 (0.81%)	13 / 1482 (0.88%)
occurrences causally related to treatment / all	0 / 12	0 / 14
deaths causally related to treatment / all	0 / 0	0 / 1
Pleural effusion
subjects affected / exposed	11 / 1474 (0.75%)	13 / 1482 (0.88%)
occurrences causally related to treatment / all	0 / 11	0 / 13
deaths causally related to treatment / all	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	9 / 1474 (0.61%)	11 / 1482 (0.74%)
occurrences causally related to treatment / all	0 / 10	0 / 11
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	10 / 1474 (0.68%)	10 / 1482 (0.67%)
occurrences causally related to treatment / all	0 / 10	0 / 10
deaths causally related to treatment / all	0 / 6	0 / 3
Pulmonary embolism
subjects affected / exposed	9 / 1474 (0.61%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	3 / 9	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 0
Epistaxis
subjects affected / exposed	4 / 1474 (0.27%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 5	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	2 / 1474 (0.14%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 3	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Interstitial lung disease
subjects affected / exposed	3 / 1474 (0.20%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1
Asthma
subjects affected / exposed	2 / 1474 (0.14%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	1 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary hypertension
subjects affected / exposed	4 / 1474 (0.27%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pleuritic pain
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary congestion
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Dyspnoea exertional
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haemoptysis
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Obstructive airways disorder
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory distress
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Apnoea
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Aspiration
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dysphonia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haemothorax
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hydrothorax
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pleurisy
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary thrombosis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary arterial hypertension
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory acidosis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Respiratory arrest
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Sleep apnoea syndrome
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Confusional state
subjects affected / exposed	1 / 1474 (0.07%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Mental status changes
subjects affected / exposed	3 / 1474 (0.20%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Depression
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Panic attack
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Adjustment disorder with depressed mood
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Adjustment disorder with mixed disturbance of emotion and conduct
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Anorexia nervosa
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bipolar disorder
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Delirium
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Disorientation
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hallucination, visual
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Major depression
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Psychotic disorder
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Suicidal ideation
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Product issues
Device malfunction
subjects affected / exposed	11 / 1474 (0.75%)	7 / 1482 (0.47%)
occurrences causally related to treatment / all	0 / 11	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombosis in device
subjects affected / exposed	4 / 1474 (0.27%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	1 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Device dislocation
subjects affected / exposed	3 / 1474 (0.20%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Device expulsion
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Device kink
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Device leakage
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Device occlusion
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	7 / 1474 (0.47%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 7	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	3 / 1474 (0.20%)	5 / 1482 (0.34%)
occurrences causally related to treatment / all	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Cholecystitis chronic
subjects affected / exposed	2 / 1474 (0.14%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic cirrhosis
subjects affected / exposed	1 / 1474 (0.07%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 1
Bile duct stone
subjects affected / exposed	2 / 1474 (0.14%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Cholangitis
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cholecystitis
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Biliary colic
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic ischaemia
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bile duct stenosis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Biliary dyskinesia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gallbladder polyp
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gallbladder rupture
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic failure
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Hepatic mass
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hydrocholecystis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ischaemic hepatitis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Transaminases increased
subjects affected / exposed	4 / 1474 (0.27%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood pressure increased
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Ejection fraction decreased
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Troponin increased
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Alanine aminotransferase increased
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haemoglobin decreased
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
International normalised ratio increased
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Anticoagulation drug level below therapeutic
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Blood pressure decreased
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood urine present
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
C-reactive protein increased
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Electrocardiogram T wave inversion
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic enzyme increased
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oxygen saturation decreased
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory syncytial virus test positive
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Staphylococcus test positive
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Troponin I increased
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Troponin T increased
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Arteriovenous fistula thrombosis
subjects affected / exposed	57 / 1474 (3.87%)	36 / 1482 (2.43%)
occurrences causally related to treatment / all	11 / 74	4 / 43
deaths causally related to treatment / all	0 / 0	0 / 0
Arteriovenous fistula site haemorrhage
subjects affected / exposed	12 / 1474 (0.81%)	12 / 1482 (0.81%)
occurrences causally related to treatment / all	0 / 12	0 / 12
deaths causally related to treatment / all	0 / 0	0 / 0
Arteriovenous graft thrombosis
subjects affected / exposed	15 / 1474 (1.02%)	7 / 1482 (0.47%)
occurrences causally related to treatment / all	0 / 25	1 / 9
deaths causally related to treatment / all	0 / 0	0 / 0
Fall
subjects affected / exposed	7 / 1474 (0.47%)	14 / 1482 (0.94%)
occurrences causally related to treatment / all	0 / 7	0 / 15
deaths causally related to treatment / all	0 / 0	0 / 0
Arteriovenous fistula site complication
subjects affected / exposed	8 / 1474 (0.54%)	9 / 1482 (0.61%)
occurrences causally related to treatment / all	0 / 10	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	5 / 1474 (0.34%)	8 / 1482 (0.54%)
occurrences causally related to treatment / all	0 / 5	0 / 9
deaths causally related to treatment / all	0 / 1	0 / 0
Vascular access site thrombosis
subjects affected / exposed	5 / 1474 (0.34%)	7 / 1482 (0.47%)
occurrences causally related to treatment / all	0 / 7	4 / 9
deaths causally related to treatment / all	0 / 0	0 / 0
Arteriovenous fistula aneurysm
subjects affected / exposed	5 / 1474 (0.34%)	6 / 1482 (0.40%)
occurrences causally related to treatment / all	0 / 7	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular access malfunction
subjects affected / exposed	5 / 1474 (0.34%)	6 / 1482 (0.40%)
occurrences causally related to treatment / all	0 / 5	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Arteriovenous fistula occlusion
subjects affected / exposed	5 / 1474 (0.34%)	5 / 1482 (0.34%)
occurrences causally related to treatment / all	0 / 5	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	5 / 1474 (0.34%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 5	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	4 / 1474 (0.27%)	5 / 1482 (0.34%)
occurrences causally related to treatment / all	0 / 4	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Pelvic fracture
subjects affected / exposed	5 / 1474 (0.34%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 5	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Ankle fracture
subjects affected / exposed	2 / 1474 (0.14%)	5 / 1482 (0.34%)
occurrences causally related to treatment / all	0 / 2	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Arteriovenous fistula site pseudoaneurysm
subjects affected / exposed	5 / 1474 (0.34%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 5	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Fibula fracture
subjects affected / exposed	1 / 1474 (0.07%)	6 / 1482 (0.40%)
occurrences causally related to treatment / all	0 / 1	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Subdural haematoma
subjects affected / exposed	4 / 1474 (0.27%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1
Arteriovenous graft site stenosis
subjects affected / exposed	2 / 1474 (0.14%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 4	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Head injury
subjects affected / exposed	6 / 1474 (0.41%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 6	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural haemorrhage
subjects affected / exposed	1 / 1474 (0.07%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	4 / 1474 (0.27%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 4	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tibia fracture
subjects affected / exposed	1 / 1474 (0.07%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular access complication
subjects affected / exposed	2 / 1474 (0.14%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1
Arteriovenous graft site haemorrhage
subjects affected / exposed	1 / 1474 (0.07%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Foot fracture
subjects affected / exposed	2 / 1474 (0.14%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Peritoneal dialysis complication
subjects affected / exposed	3 / 1474 (0.20%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Shunt thrombosis
subjects affected / exposed	3 / 1474 (0.20%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 3	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Thermal burn
subjects affected / exposed	3 / 1474 (0.20%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Acetabulum fracture
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Clavicle fracture
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Contusion
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Dialysis related complication
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hand fracture
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Limb injury
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Patella fracture
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural haematoma
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Procedural haemorrhage
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Shunt blood flow excessive
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal compression fracture
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Toxicity to various agents
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular access steal syndrome
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Arteriovenous fistula site haematoma
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Facial bones fracture
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Graft thrombosis
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Joint dislocation
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Joint injury
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Lower limb fracture
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Poisoning
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Postoperative wound complication
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular access site haemorrhage
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular graft occlusion
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular pseudoaneurysm
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular pseudoaneurysm ruptured
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Anaemia postoperative
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Aortic pseudoaneurysm
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Arteriovenous graft aneurysm
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchial injury
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Burns second degree
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cervical vertebral fracture
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Delayed recovery from anaesthesia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Delayed graft function
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Fractured sacrum
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Foreign body in gastrointestinal tract
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Forearm fracture
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Graft loss
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Implantation complication
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Keratorhexis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lumbar vertebral fracture
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Meniscus injury
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Muscle rupture
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Multiple injuries
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Multiple fractures
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Periorbital haematoma
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural hypotension
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural inflammation
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural swelling
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural urine leak
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Postoperative hypertension
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Procedural pain
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Restenosis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Shunt aneurysm
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skeletal injury
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Skin laceration
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skull fracture
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal fracture
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Spinal cord injury
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sternal fracture
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Subdural haemorrhage
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tendon injury
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thoracic vertebral fracture
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Traumatic fracture
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular access site swelling
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular graft complication
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular graft thrombosis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular pseudoaneurysm thrombosis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vena cava injury
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Wound necrosis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital, familial and genetic disorders
Atrial septal defect
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital cystic kidney disease
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Protein C deficiency
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	31 / 1474 (2.10%)	30 / 1482 (2.02%)
occurrences causally related to treatment / all	3 / 40	4 / 33
deaths causally related to treatment / all	0 / 1	0 / 1
Atrial fibrillation
subjects affected / exposed	35 / 1474 (2.37%)	23 / 1482 (1.55%)
occurrences causally related to treatment / all	0 / 44	1 / 26
deaths causally related to treatment / all	0 / 1	0 / 0
Cardiac arrest
subjects affected / exposed	15 / 1474 (1.02%)	20 / 1482 (1.35%)
occurrences causally related to treatment / all	0 / 15	1 / 20
deaths causally related to treatment / all	0 / 8	1 / 18
Angina pectoris
subjects affected / exposed	16 / 1474 (1.09%)	18 / 1482 (1.21%)
occurrences causally related to treatment / all	1 / 18	0 / 19
deaths causally related to treatment / all	0 / 0	0 / 1
Cardiac failure
subjects affected / exposed	15 / 1474 (1.02%)	18 / 1482 (1.21%)
occurrences causally related to treatment / all	0 / 15	1 / 23
deaths causally related to treatment / all	0 / 1	0 / 4
Cardiac failure congestive
subjects affected / exposed	15 / 1474 (1.02%)	18 / 1482 (1.21%)
occurrences causally related to treatment / all	1 / 19	0 / 19
deaths causally related to treatment / all	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	17 / 1474 (1.15%)	11 / 1482 (0.74%)
occurrences causally related to treatment / all	1 / 17	2 / 11
deaths causally related to treatment / all	1 / 4	0 / 2
Angina unstable
subjects affected / exposed	13 / 1474 (0.88%)	14 / 1482 (0.94%)
occurrences causally related to treatment / all	1 / 15	0 / 14
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	16 / 1474 (1.09%)	10 / 1482 (0.67%)
occurrences causally related to treatment / all	1 / 16	2 / 11
deaths causally related to treatment / all	0 / 0	0 / 0
Acute coronary syndrome
subjects affected / exposed	10 / 1474 (0.68%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 10	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Cardio-respiratory arrest
subjects affected / exposed	5 / 1474 (0.34%)	8 / 1482 (0.54%)
occurrences causally related to treatment / all	0 / 5	1 / 8
deaths causally related to treatment / all	0 / 2	1 / 6
Bradycardia
subjects affected / exposed	8 / 1474 (0.54%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 8	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Acute left ventricular failure
subjects affected / exposed	5 / 1474 (0.34%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	1 / 6	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	5 / 1474 (0.34%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 5	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure acute
subjects affected / exposed	1 / 1474 (0.07%)	8 / 1482 (0.54%)
occurrences causally related to treatment / all	0 / 1	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 1
Aortic valve stenosis
subjects affected / exposed	5 / 1474 (0.34%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 5	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pericardial effusion
subjects affected / exposed	4 / 1474 (0.27%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 6	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Atrioventricular block complete
subjects affected / exposed	4 / 1474 (0.27%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Mitral valve incompetence
subjects affected / exposed	2 / 1474 (0.14%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	1 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Myocardial ischaemia
subjects affected / exposed	2 / 1474 (0.14%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 1
Pericarditis
subjects affected / exposed	3 / 1474 (0.20%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac tamponade
subjects affected / exposed	3 / 1474 (0.20%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Congestive cardiomyopathy
subjects affected / exposed	1 / 1474 (0.07%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Right ventricular failure
subjects affected / exposed	2 / 1474 (0.14%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Sinus bradycardia
subjects affected / exposed	3 / 1474 (0.20%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Supraventricular tachycardia
subjects affected / exposed	2 / 1474 (0.14%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Ventricular tachycardia
subjects affected / exposed	1 / 1474 (0.07%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Atrioventricular block
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiogenic shock
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1
Cardiomyopathy
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery stenosis
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sinus node dysfunction
subjects affected / exposed	3 / 1474 (0.20%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery occlusion
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ischaemic cardiomyopathy
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Nodal arrhythmia
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pericarditis uraemic
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Pulseless electrical activity
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Stress cardiomyopathy
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tachycardia
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ventricular fibrillation
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Aortic valve incompetence
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Arrhythmia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial thrombosis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial tachycardia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Atrioventricular block second degree
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bradyarrhythmia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac discomfort
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiomegaly
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Chronic left ventricular failure
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Endocarditis noninfective
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Left ventricular dysfunction
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Left ventricular failure
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Mitral valve calcification
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Myocarditis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nodal rhythm
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Palpitations
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pericardial haemorrhage
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sinus tachycardia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Subendocardial ischaemia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ventricular arrhythmia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Ischaemic stroke
subjects affected / exposed	11 / 1474 (0.75%)	11 / 1482 (0.74%)
occurrences causally related to treatment / all	1 / 11	1 / 11
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	11 / 1474 (0.75%)	9 / 1482 (0.61%)
occurrences causally related to treatment / all	2 / 13	1 / 11
deaths causally related to treatment / all	0 / 5	0 / 3
Syncope
subjects affected / exposed	13 / 1474 (0.88%)	5 / 1482 (0.34%)
occurrences causally related to treatment / all	0 / 13	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	10 / 1474 (0.68%)	7 / 1482 (0.47%)
occurrences causally related to treatment / all	0 / 12	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolic encephalopathy
subjects affected / exposed	9 / 1474 (0.61%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 10	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Seizure
subjects affected / exposed	5 / 1474 (0.34%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 5	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Encephalopathy
subjects affected / exposed	4 / 1474 (0.27%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 5	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebral infarction
subjects affected / exposed	3 / 1474 (0.20%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	1 / 3	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0
Hypertensive encephalopathy
subjects affected / exposed	2 / 1474 (0.14%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Carotid artery stenosis
subjects affected / exposed	2 / 1474 (0.14%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebral haemorrhage
subjects affected / exposed	2 / 1474 (0.14%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 2
Carpal tunnel syndrome
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dizziness
subjects affected / exposed	3 / 1474 (0.20%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Facial paralysis
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Sciatica
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Toxic encephalopathy
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Generalised tonic-clonic seizure
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhagic stroke
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 2
Headache
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic encephalopathy
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Hypocalcaemic seizure
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorder
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Thalamus haemorrhage
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tremor
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Uraemic encephalopathy
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Altered state of consciousness
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Aphasia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Brain injury
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Brain stem infarction
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Brain stem ischaemia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebellar stroke
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebral artery stenosis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebral circulatory failure
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cognitive disorder
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Coma
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dysarthria
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dyskinesia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Embolic stroke
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Focal dyscognitive seizures
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhage intracranial
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
IIIrd nerve paralysis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intraventricular haemorrhage
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Intracranial aneurysm
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Loss of consciousness
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lumbar radiculopathy
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Myelopathy
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Neuropathy peripheral
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Neurotoxicity
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pachymeningitis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Paraesthesia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Parkinson's disease
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Partial seizures
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Post herpetic neuralgia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Polyneuropathy
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Postictal state
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Presyncope
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Seizure cluster
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Somnolence
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Subarachnoid haemorrhage
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
VIth nerve paralysis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	41 / 1474 (2.78%)	26 / 1482 (1.75%)
occurrences causally related to treatment / all	3 / 52	0 / 29
deaths causally related to treatment / all	0 / 0	0 / 1
Blood loss anaemia
subjects affected / exposed	3 / 1474 (0.20%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Lymphadenitis
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Aplastic anaemia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Coagulopathy
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cytopenia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Leukocytosis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Leukopenia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lymphadenopathy
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Non-immune heparin associated thrombocytopenia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Normocytic anaemia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Deafness bilateral
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Deafness unilateral
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypoacusis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Inner ear disorder
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Cataract
subjects affected / exposed	5 / 1474 (0.34%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 6	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Retinal artery occlusion
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Vitreous haemorrhage
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cataract nuclear
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic retinopathy
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diplopia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Eye pain
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Eye haemorrhage
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Eyelid ptosis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Glaucoma
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Macular fibrosis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ophthalmoplegia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Retinopathy
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Retinal detachment
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Retinal artery embolism
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sympathetic ophthalmia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tolosa-Hunt syndrome
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ulcerative keratitis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Gastrointestinal haemorrhage
subjects affected / exposed	11 / 1474 (0.75%)	12 / 1482 (0.81%)
occurrences causally related to treatment / all	0 / 12	0 / 13
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	7 / 1474 (0.47%)	6 / 1482 (0.40%)
occurrences causally related to treatment / all	0 / 7	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Ascites
subjects affected / exposed	4 / 1474 (0.27%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 4	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Gastric ulcer
subjects affected / exposed	5 / 1474 (0.34%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 5	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Gastritis erosive
subjects affected / exposed	1 / 1474 (0.07%)	7 / 1482 (0.47%)
occurrences causally related to treatment / all	0 / 1	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	6 / 1474 (0.41%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 6	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	4 / 1474 (0.27%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 4	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	2 / 1474 (0.14%)	5 / 1482 (0.34%)
occurrences causally related to treatment / all	0 / 2	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Duodenal ulcer
subjects affected / exposed	4 / 1474 (0.27%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	3 / 1474 (0.20%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis
subjects affected / exposed	3 / 1474 (0.20%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis ischaemic
subjects affected / exposed	4 / 1474 (0.27%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Gastritis
subjects affected / exposed	3 / 1474 (0.20%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrooesophageal reflux disease
subjects affected / exposed	5 / 1474 (0.34%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 5	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Chronic gastritis
subjects affected / exposed	2 / 1474 (0.14%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Constipation
subjects affected / exposed	4 / 1474 (0.27%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhoids
subjects affected / exposed	2 / 1474 (0.14%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal ischaemia
subjects affected / exposed	3 / 1474 (0.20%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0
Small intestinal obstruction
subjects affected / exposed	2 / 1474 (0.14%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 2	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Umbilical hernia
subjects affected / exposed	2 / 1474 (0.14%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic gastroparesis
subjects affected / exposed	1 / 1474 (0.07%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Duodenal ulcer haemorrhage
subjects affected / exposed	0 / 1474 (0.00%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 1
Gastric ulcer haemorrhage
subjects affected / exposed	2 / 1474 (0.14%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Lower gastrointestinal haemorrhage
subjects affected / exposed	2 / 1474 (0.14%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatitis chronic
subjects affected / exposed	2 / 1474 (0.14%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulum
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhoidal haemorrhage
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Impaired gastric emptying
subjects affected / exposed	0 / 1474 (0.00%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal haemorrhage
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	1 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	3 / 1474 (0.20%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vomiting
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal adhesions
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal hernia
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dieulafoy's vascular malformation
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulum intestinal
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Faecaloma
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastric polyps
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroduodenal ulcer
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal angiectasia
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal polyp haemorrhage
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal vascular malformation haemorrhagic
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haematochezia
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ileus
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Obstructive pancreatitis
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophageal ulcer haemorrhage
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophagitis
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumoperitoneum
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Retroperitoneal haemorrhage
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal wall haemorrhage
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Alcoholic pancreatitis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Anal inflammation
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Anal fistula
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Anal fissure
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Crohn's disease
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Discoloured vomit
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulum intestinal haemorrhagic
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Duodenal ulcer perforation
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Duodenitis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dysphagia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Enteritis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Epiploic appendagitis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Enterocolitis haemorrhagic
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Erosive oesophagitis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastric dysplasia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastric disorder
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastric haemorrhage
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastric mucosa erythema
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastric perforation
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal erosion
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal obstruction
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gingival bleeding
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhagic necrotic pancreatitis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhagic erosive gastritis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haemoperitoneum
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hiatus hernia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ileus paralytic
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Incarcerated umbilical hernia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal perforation
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intussusception
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Irritable bowel syndrome
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Large intestine polyp
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Large intestinal haemorrhage
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lumbar hernia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Mallory-Weiss syndrome
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Mechanical ileus
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nausea
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophageal perforation
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophageal motility disorder
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophageal ulcer
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophagitis ulcerative
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal ulcer
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Retroperitoneal haematoma
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Small intestinal perforation
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ulcerative gastritis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Diabetic foot
subjects affected / exposed	3 / 1474 (0.20%)	8 / 1482 (0.54%)
occurrences causally related to treatment / all	0 / 3	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0
Skin ulcer
subjects affected / exposed	1 / 1474 (0.07%)	7 / 1482 (0.47%)
occurrences causally related to treatment / all	0 / 1	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Decubitus ulcer
subjects affected / exposed	3 / 1474 (0.20%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Angioedema
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Blister
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic wound
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperkeratosis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ischaemic skin ulcer
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin weeping
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urticaria
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Chronic kidney disease
subjects affected / exposed	5 / 1474 (0.34%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 5	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0
Azotaemia
subjects affected / exposed	4 / 1474 (0.27%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
End stage renal disease
subjects affected / exposed	1 / 1474 (0.07%)	5 / 1482 (0.34%)
occurrences causally related to treatment / all	0 / 1	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 3
Haematuria
subjects affected / exposed	4 / 1474 (0.27%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cystitis haemorrhagic
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hydronephrosis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lupus nephritis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal artery thrombosis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal disorder
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal cyst ruptured
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal cyst haemorrhage
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal failure
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Stag horn calculus
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Subcapsular renal haematoma
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract obstruction
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract disorder
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Endocrine disorders
Hyperparathyroidism
subjects affected / exposed	2 / 1474 (0.14%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperparathyroidism secondary
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Adrenal insufficiency
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperparathyroidism tertiary
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Goitre
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Secondary adrenocortical insufficiency
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
subjects affected / exposed	6 / 1474 (0.41%)	5 / 1482 (0.34%)
occurrences causally related to treatment / all	0 / 6	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	6 / 1474 (0.41%)	5 / 1482 (0.34%)
occurrences causally related to treatment / all	0 / 6	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Bursitis
subjects affected / exposed	4 / 1474 (0.27%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Back pain
subjects affected / exposed	2 / 1474 (0.14%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Arthralgia
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Costochondritis
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haematoma muscle
subjects affected / exposed	3 / 1474 (0.20%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hungry bone syndrome
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Osteonecrosis
subjects affected / exposed	3 / 1474 (0.20%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pathological fracture
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal stenosis
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cervical spinal stenosis
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Flank pain
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Arthritis reactive
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Chondropathy
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Chest wall haematoma
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Compartment syndrome
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
High turnover osteopathy
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lumbar spinal stenosis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Muscular weakness
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Myalgia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal pain
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Myositis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Neuropathic arthropathy
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Osteitis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Osteoporosis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sacroiliitis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rhabdomyolysis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rheumatoid arthritis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal osteoarthritis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Spondylitis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tendon disorder
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Synovitis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Synovial cyst
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tenosynovitis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	81 / 1474 (5.50%)	86 / 1482 (5.80%)
occurrences causally related to treatment / all	0 / 96	1 / 97
deaths causally related to treatment / all	0 / 2	0 / 4
Sepsis
subjects affected / exposed	37 / 1474 (2.51%)	29 / 1482 (1.96%)
occurrences causally related to treatment / all	0 / 37	0 / 31
deaths causally related to treatment / all	0 / 4	0 / 11
Peritonitis
subjects affected / exposed	24 / 1474 (1.63%)	31 / 1482 (2.09%)
occurrences causally related to treatment / all	0 / 34	0 / 42
deaths causally related to treatment / all	0 / 1	0 / 2
COVID-19
subjects affected / exposed	22 / 1474 (1.49%)	22 / 1482 (1.48%)
occurrences causally related to treatment / all	0 / 22	0 / 22
deaths causally related to treatment / all	0 / 3	0 / 5
Cellulitis
subjects affected / exposed	21 / 1474 (1.42%)	16 / 1482 (1.08%)
occurrences causally related to treatment / all	0 / 26	0 / 18
deaths causally related to treatment / all	0 / 0	0 / 0
Gangrene
subjects affected / exposed	19 / 1474 (1.29%)	15 / 1482 (1.01%)
occurrences causally related to treatment / all	0 / 28	0 / 19
deaths causally related to treatment / all	0 / 0	0 / 1
Osteomyelitis
subjects affected / exposed	13 / 1474 (0.88%)	15 / 1482 (1.01%)
occurrences causally related to treatment / all	0 / 16	0 / 18
deaths causally related to treatment / all	0 / 0	0 / 0
Septic shock
subjects affected / exposed	16 / 1474 (1.09%)	8 / 1482 (0.54%)
occurrences causally related to treatment / all	0 / 17	0 / 9
deaths causally related to treatment / all	0 / 5	0 / 3
Urinary tract infection
subjects affected / exposed	11 / 1474 (0.75%)	13 / 1482 (0.88%)
occurrences causally related to treatment / all	0 / 16	0 / 14
deaths causally related to treatment / all	0 / 0	0 / 0
Device related infection
subjects affected / exposed	9 / 1474 (0.61%)	13 / 1482 (0.88%)
occurrences causally related to treatment / all	0 / 10	0 / 14
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	13 / 1474 (0.88%)	9 / 1482 (0.61%)
occurrences causally related to treatment / all	0 / 15	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	11 / 1474 (0.75%)	9 / 1482 (0.61%)
occurrences causally related to treatment / all	0 / 11	0 / 10
deaths causally related to treatment / all	0 / 1	0 / 0
Staphylococcal sepsis
subjects affected / exposed	10 / 1474 (0.68%)	10 / 1482 (0.67%)
occurrences causally related to treatment / all	0 / 10	0 / 10
deaths causally related to treatment / all	0 / 1	0 / 0
Influenza
subjects affected / exposed	11 / 1474 (0.75%)	8 / 1482 (0.54%)
occurrences causally related to treatment / all	0 / 11	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Arteriovenous fistula site infection
subjects affected / exposed	6 / 1474 (0.41%)	12 / 1482 (0.81%)
occurrences causally related to treatment / all	0 / 6	0 / 13
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	7 / 1474 (0.47%)	8 / 1482 (0.54%)
occurrences causally related to treatment / all	0 / 8	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Staphylococcal bacteraemia
subjects affected / exposed	7 / 1474 (0.47%)	8 / 1482 (0.54%)
occurrences causally related to treatment / all	0 / 9	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0
Peritonitis bacterial
subjects affected / exposed	8 / 1474 (0.54%)	6 / 1482 (0.40%)
occurrences causally related to treatment / all	0 / 14	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Device related sepsis
subjects affected / exposed	6 / 1474 (0.41%)	7 / 1482 (0.47%)
occurrences causally related to treatment / all	0 / 7	0 / 11
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic foot infection
subjects affected / exposed	6 / 1474 (0.41%)	7 / 1482 (0.47%)
occurrences causally related to treatment / all	0 / 6	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	8 / 1474 (0.54%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 9	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	5 / 1474 (0.34%)	7 / 1482 (0.47%)
occurrences causally related to treatment / all	0 / 5	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 1
Bacteraemia
subjects affected / exposed	7 / 1474 (0.47%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 7	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Staphylococcal infection
subjects affected / exposed	3 / 1474 (0.20%)	8 / 1482 (0.54%)
occurrences causally related to treatment / all	0 / 3	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0
Postoperative wound infection
subjects affected / exposed	4 / 1474 (0.27%)	6 / 1482 (0.40%)
occurrences causally related to treatment / all	0 / 4	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 1
Arteriovenous graft site infection
subjects affected / exposed	5 / 1474 (0.34%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 5	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	4 / 1474 (0.27%)	5 / 1482 (0.34%)
occurrences causally related to treatment / all	0 / 4	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Endocarditis
subjects affected / exposed	3 / 1474 (0.20%)	6 / 1482 (0.40%)
occurrences causally related to treatment / all	0 / 3	0 / 6
deaths causally related to treatment / all	0 / 1	0 / 1
Gastroenteritis viral
subjects affected / exposed	6 / 1474 (0.41%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 6	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Abscess limb
subjects affected / exposed	3 / 1474 (0.20%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 3	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Catheter site infection
subjects affected / exposed	2 / 1474 (0.14%)	5 / 1482 (0.34%)
occurrences causally related to treatment / all	0 / 2	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Localised infection
subjects affected / exposed	5 / 1474 (0.34%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 5	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Arthritis bacterial
subjects affected / exposed	3 / 1474 (0.20%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural infection
subjects affected / exposed	5 / 1474 (0.34%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 5	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular device infection
subjects affected / exposed	4 / 1474 (0.27%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 5	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	4 / 1474 (0.27%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	2 / 1474 (0.14%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Infected skin ulcer
subjects affected / exposed	3 / 1474 (0.20%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Intervertebral discitis
subjects affected / exposed	2 / 1474 (0.14%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia viral
subjects affected / exposed	3 / 1474 (0.20%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular access site infection
subjects affected / exposed	1 / 1474 (0.07%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Wound infection
subjects affected / exposed	3 / 1474 (0.20%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Anal abscess
subjects affected / exposed	2 / 1474 (0.14%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic gangrene
subjects affected / exposed	2 / 1474 (0.14%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Escherichia sepsis
subjects affected / exposed	2 / 1474 (0.14%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Fungal peritonitis
subjects affected / exposed	0 / 1474 (0.00%)	4 / 1482 (0.27%)
occurrences causally related to treatment / all	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Infection
subjects affected / exposed	1 / 1474 (0.07%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia influenzal
subjects affected / exposed	4 / 1474 (0.27%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Suspected COVID-19
subjects affected / exposed	1 / 1474 (0.07%)	3 / 1482 (0.20%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Device related bacteraemia
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Cystitis
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Enterobacter sepsis
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Endocarditis bacterial
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	1 / 2
Erysipelas
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Escherichia infection
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatitis C
subjects affected / exposed	3 / 1474 (0.20%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Klebsiella infection
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia streptococcal
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary tuberculosis
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis chronic
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1
Respiratory tract infection
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Streptococcal sepsis
subjects affected / exposed	3 / 1474 (0.20%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Viral upper respiratory tract infection
subjects affected / exposed	1 / 1474 (0.07%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal wall abscess
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal sepsis
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Acute hepatitis B
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Appendicitis perforated
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Arthritis infective
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Atypical pneumonia
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Bacterial infection
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Carbuncle
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cholecystitis infective
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Clostridium difficile infection
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colonic abscess
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Endocarditis staphylococcal
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gas gangrene
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic cyst infection
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infectious pleural effusion
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Klebsiella bacteraemia
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Klebsiella sepsis
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Large intestine infection
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Lung abscess
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lymph node tuberculosis
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nasopharyngitis
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Otitis externa
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Parainfluenzae virus infection
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Proteus infection
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pseudomonal sepsis
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary sepsis
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal cyst infection
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rhinovirus infection
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Scrotal abscess
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tuberculosis
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Varicella
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal abscess
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Abscess neck
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Acinetobacter bacteraemia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Arteriovenous graft site abscess
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bacterial sepsis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Biliary sepsis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Bone abscess
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bone tuberculosis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Boutonneuse fever
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Burn infection
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Candida pneumonia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bursitis infective
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Campylobacter gastroenteritis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Catheter site abscess
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Complicated appendicitis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dengue fever
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea infectious
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Douglas' abscess
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Enteritis infectious
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Enterobacter bacteraemia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Enterobacter infection
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Endophthalmitis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Enterococcal sepsis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Enterococcal bacteraemia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Enterobacter pneumonia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Escherichia peritonitis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Escherichia bacteraemia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile infection
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Furuncle
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Fungal oesophagitis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Fungaemia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis bacterial
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis staphylococcal
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Graft infection
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Groin infection
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Groin abscess
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic echinococciasis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Helicobacter gastritis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatitis B
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Herpes zoster meningitis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Herpes ophthalmic
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infected cyst
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infected fistula
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infective aneurysm
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infective exacerbation of chronic obstructive airways disease
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Kidney infection
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Listeraemia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Listeria sepsis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Liver abscess
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Mastoiditis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Measles
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Meningitis aseptic
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Meningitis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Mesenteric abscess
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metapneumovirus infection
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophageal candidiasis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Osteomyelitis chronic
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Osteomyelitis acute
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Orchitis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Otitis media
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Paronychia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pericarditis infective
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pelvic infection
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Parotitis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumocystis jirovecii pneumonia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia haemophilus
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural sepsis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Postoperative abscess
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyuria
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory syncytial virus infection
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory tract infection viral
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Retroperitoneal infection
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Salmonella sepsis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Septic embolus
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Septic encephalopathy
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Shigella infection
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Shunt infection
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sinusitis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin infection
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Soft tissue infection
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Staphylococcal osteomyelitis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Streptococcal endocarditis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tooth infection
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tooth abscess
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tonsillitis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tracheitis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tracheobronchitis
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vestibulitis
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Fluid overload
subjects affected / exposed	45 / 1474 (3.05%)	42 / 1482 (2.83%)
occurrences causally related to treatment / all	0 / 57	0 / 53
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	36 / 1474 (2.44%)	19 / 1482 (1.28%)
occurrences causally related to treatment / all	0 / 41	0 / 23
deaths causally related to treatment / all	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	9 / 1474 (0.61%)	11 / 1482 (0.74%)
occurrences causally related to treatment / all	0 / 10	0 / 12
deaths causally related to treatment / all	0 / 0	0 / 1
Hypervolaemia
subjects affected / exposed	3 / 1474 (0.20%)	5 / 1482 (0.34%)
occurrences causally related to treatment / all	0 / 3	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	2 / 1474 (0.14%)	5 / 1482 (0.34%)
occurrences causally related to treatment / all	0 / 2	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	4 / 1474 (0.27%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Dehydration
subjects affected / exposed	4 / 1474 (0.27%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypocalcaemia
subjects affected / exposed	3 / 1474 (0.20%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic ketoacidosis
subjects affected / exposed	2 / 1474 (0.14%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Malnutrition
subjects affected / exposed	2 / 1474 (0.14%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 1
Diabetes mellitus inadequate control
subjects affected / exposed	2 / 1474 (0.14%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	3 / 1474 (0.20%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Calciphylaxis
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetes mellitus
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic metabolic decompensation
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Fluid retention
subjects affected / exposed	2 / 1474 (0.14%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolic acidosis
subjects affected / exposed	1 / 1474 (0.07%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Type 1 diabetes mellitus
subjects affected / exposed	0 / 1474 (0.00%)	2 / 1482 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic complication
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Electrolyte imbalance
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypovolaemia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypophagia
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypoalbuminaemia
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Insulin-requiring type 2 diabetes mellitus
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Obesity
subjects affected / exposed	1 / 1474 (0.07%)	0 / 1482 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vitamin B12 deficiency
subjects affected / exposed	0 / 1474 (0.00%)	1 / 1482 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	rhEPO	Daprodustat
Total subjects affected by non serious adverse events
subjects affected / exposed	827 / 1474 (56.11%)	830 / 1482 (56.01%)
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	84 / 1474 (5.70%)	73 / 1482 (4.93%)
occurrences all number	119	96
Arteriovenous fistula site complication
subjects affected / exposed	89 / 1474 (6.04%)	61 / 1482 (4.12%)
occurrences all number	121	90
Vascular disorders
Hypertension
subjects affected / exposed	232 / 1474 (15.74%)	235 / 1482 (15.86%)
occurrences all number	356	366
Dialysis hypotension
subjects affected / exposed	105 / 1474 (7.12%)	135 / 1482 (9.11%)
occurrences all number	206	254
Hypotension
subjects affected / exposed	92 / 1474 (6.24%)	115 / 1482 (7.76%)
occurrences all number	130	140
Nervous system disorders
Headache
subjects affected / exposed	139 / 1474 (9.43%)	115 / 1482 (7.76%)
occurrences all number	216	176
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	176 / 1474 (11.94%)	161 / 1482 (10.86%)
occurrences all number	228	225
Nausea
subjects affected / exposed	84 / 1474 (5.70%)	83 / 1482 (5.60%)
occurrences all number	106	95
Vomiting
subjects affected / exposed	76 / 1474 (5.16%)	83 / 1482 (5.60%)
occurrences all number	98	103
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	101 / 1474 (6.85%)	101 / 1482 (6.82%)
occurrences all number	133	128
Dyspnoea
subjects affected / exposed	74 / 1474 (5.02%)	58 / 1482 (3.91%)
occurrences all number	88	67
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	111 / 1474 (7.53%)	101 / 1482 (6.82%)
occurrences all number	138	120
Pain in extremity
subjects affected / exposed	76 / 1474 (5.16%)	85 / 1482 (5.74%)
occurrences all number	99	105
Back pain
subjects affected / exposed	88 / 1474 (5.97%)	64 / 1482 (4.32%)
occurrences all number	103	87
Infections and infestations
Nasopharyngitis
subjects affected / exposed	104 / 1474 (7.06%)	113 / 1482 (7.62%)
occurrences all number	188	188
Upper respiratory tract infection
subjects affected / exposed	92 / 1474 (6.24%)	99 / 1482 (6.68%)
occurrences all number	125	144
Bronchitis
subjects affected / exposed	97 / 1474 (6.58%)	87 / 1482 (5.87%)
occurrences all number	124	116
Urinary tract infection
subjects affected / exposed	79 / 1474 (5.36%)	73 / 1482 (4.93%)
occurrences all number	97	99
Metabolism and nutrition disorders
Hyperkalaemia
subjects affected / exposed	62 / 1474 (4.21%)	76 / 1482 (5.13%)
occurrences all number	72	92

More information

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Were there any global substantial amendments to the protocol? Yes

20 Sep 2016

Amendment 1: Applies to Austria, Belgium, Czech Republic, Denmark, Estonia, Germany, Hungary, Italy, Norway, Poland, Portugal, Romania, Spain, Sweden and UK. Clarified end of the study; removal of requirement to reduce ESA dose if W-8 Hgb is >11.5 g/dL; guidance to iron management; new exploratory objective to compare daprodustat to rhEPO on delayed graft function after deceased donor kidney transplantation

12 Oct 2016

Amendment 2: Main changes include new timepoints at Run-in (Week -4) and Week 2 for collection of iron therapy and at Week 52 for Kt/Vurea. Changes to ABPM assessments and prompts for recording awaking and sleeping times; clarification for those randomized to rhEPO who transition from HD to PD will change from epoetin alfa to darbepoetin alfa.

08 Feb 2017

Amendment 2/France1: Additional ultrasound added to France; PD participants are not eligible for France.

05 Oct 2017

Amendment 3: Added retest for Hgb and TSAT to determine eligibility; broadened exclusion to include participation in interventional study with investigational agent or device; revised statistical section to change from two-sided testing at the 5% level to onesided testing at the 2.5% level; correct the comparator for the Null and Alternative hypotheses; changed significance levels to p-values; added description of the adjustments to statistical model; updated hyporesponder analyses; added text regarding the interim analysis process; added exploratory endpoints around Hgb variability, iron parameters, transfusions and dose adjustment scheme; provision for possible adjustment to Dose Adjustment Algorithm triggers for Hgb values 7.5 g/dL to <9.5 g/dL based on the review of blinded instream aggregate Hgb data

09 Oct 2017

Amendment 3/France1: Changes from amendment 3 to France

30 Jul 2020

Amendment 4: Revised MACE non-inferiority margin NI margin; revised target MACE as a result of the change to the NI margin; updated the analysis of the hemoglobin co-primary endpoint based on FDA feedback; multiplicity adjustment strategy updated from Hommel to Holm-Bonferroni based on FDA feedback; added AESI of worsening of hypertension

30 Jul 2020

Amendment 4/France1: changes from amendment 4 to France

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Time to first occurrence of adjudicated major adverse cardiovascular event (MACE) during cardiovascular (CV) events follow-up time period: Non-inferiority analysis

Primary: Time to first occurrence of adjudicated major adverse cardiovascular event (MACE) during cardiovascular (CV) events follow-up time period: Non-inferiority analysis

Primary: Mean Change from Baseline in Hemoglobin (Hgb) levels During Evaluation Period (Week 28 to Week 52)

Primary: Mean Change from Baseline in Hemoglobin (Hgb) levels During Evaluation Period (Week 28 to Week 52)

Secondary: Time to first occurrence of adjudicated MACE during CV events follow-up time period: Superiority analysis

Secondary: Time to first occurrence of adjudicated MACE during CV events follow-up time period: Superiority analysis

Secondary: Time to first occurrence of adjudicated MACE or thromboembolic event during CV events follow-up time period

Secondary: Time to first occurrence of adjudicated MACE or thromboembolic event during CV events follow-up time period

Secondary: Time to first occurrence of adjudicated MACE or hospitalization for heart failure during CV events follow-up time period

Secondary: Time to first occurrence of adjudicated MACE or hospitalization for heart failure during CV events follow-up time period

Secondary: Mean average monthly On-treatment IV iron dose per participant

Secondary: Mean average monthly On-treatment IV iron dose per participant

Secondary: Time to First occurrence of Adjudicated All-Cause Mortality during vital status for follow-up time period

Secondary: Time to First occurrence of Adjudicated All-Cause Mortality during vital status for follow-up time period

Secondary: Time to First occurrence of Adjudicated CV Mortality during CV events follow-up time period

Secondary: Time to First occurrence of Adjudicated CV Mortality during CV events follow-up time period

Secondary: Time to First occurrence of Adjudicated Myocardial Infarction (MI) (Fatal and Non-Fatal) during CV events follow-up time period

Secondary: Time to First occurrence of Adjudicated Myocardial Infarction (MI) (Fatal and Non-Fatal) during CV events follow-up time period

Secondary: Time to First occurrence of Adjudicated Stroke (Fatal and Non-Fatal) during CV events follow-up time period

Secondary: Time to First occurrence of Adjudicated Stroke (Fatal and Non-Fatal) during CV events follow-up time period

Secondary: Number of participants with Adjudicated MACE or Hospitalization for Heart Failure (Recurrent events analysis)

Secondary: Number of participants with Adjudicated MACE or Hospitalization for Heart Failure (Recurrent events analysis)

Secondary: Time to First Occurrence of Adjudicated CV Mortality or Non-Fatal MI during CV events follow-up time period

Secondary: Time to First Occurrence of Adjudicated CV Mortality or Non-Fatal MI during CV events follow-up time period

Secondary: Time to First Occurrence of All-Cause Hospitalization during CV events follow-up time period

Secondary: Time to First Occurrence of All-Cause Hospitalization during CV events follow-up time period

Secondary: Time to First Occurrence of All-Cause Hospital Re-admission within 30 Days during CV events follow-up time period

Secondary: Time to First Occurrence of All-Cause Hospital Re-admission within 30 Days during CV events follow-up time period

Secondary: Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure or Thromboembolic events during CV events follow-up time period

Secondary: Time to First Occurrence of Adjudicated MACE or Hospitalization for Heart Failure or Thromboembolic events during CV events follow-up time period

Secondary: Time to First Occurrence of Adjudicated Hospitalization for Heart Failure during CV events follow-up time period

Secondary: Time to First Occurrence of Adjudicated Hospitalization for Heart Failure during CV events follow-up time period

Secondary: Time to First Occurrence of Adjudicated Thromboembolic Events during CV events follow-up time period

Secondary: Time to First Occurrence of Adjudicated Thromboembolic Events during CV events follow-up time period

Secondary: Change From Baseline in Post-randomization Hemoglobin levels at Week 52

Secondary: Change From Baseline in Post-randomization Hemoglobin levels at Week 52

Secondary: Number of Hgb Responders in the Hgb Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52)

Secondary: Number of Hgb Responders in the Hgb Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52)

Secondary: Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Non-inferiority analysis

Secondary: Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Non-inferiority analysis

Secondary: Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Superiority analysis

Secondary: Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52): Superiority analysis

Secondary: Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of study): Non-inferiority analysis

Secondary: Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of study): Non-inferiority analysis

Secondary: Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of study): Superiority analysis

Secondary: Percentage of Time With Hemoglobin in the Analysis Range (10 to 11.5 Grams/Deciliter) During Maintenance Period (Week 28 to End of study): Superiority analysis

Secondary: Change from Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52

Secondary: Change from Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Blood Pressure (MAP) at Week 52

Secondary: Change from Baseline in SBP, DBP, MAP at End of Treatment

Secondary: Change from Baseline in SBP, DBP, MAP at End of Treatment

Secondary: Blood Pressure (BP) Exacerbation Event Rate per 100 Participant Years

Secondary: Blood Pressure (BP) Exacerbation Event Rate per 100 Participant Years

Secondary: Number of Participants with at Least one BP Exacerbation Event During Study

Secondary: Number of Participants with at Least one BP Exacerbation Event During Study

Secondary: Percentage of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria

Secondary: Percentage of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria

Secondary: Change from Baseline in On-Treatment Physical Component Score (PCS) using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52

Secondary: Change from Baseline in On-Treatment Physical Component Score (PCS) using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52

Secondary: Change from Baseline in On-Treatment Mental Component Score (MCS) using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

Secondary: Change from Baseline in On-Treatment Mental Component Score (MCS) using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

Secondary: Change from Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52

Secondary: Change from Baseline in On-Treatment SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52

Secondary: Change from Baseline in On-Treatment Vitality scores using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

Secondary: Change from Baseline in On-Treatment Vitality scores using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

Secondary: Change from Baseline in On-Treatment Physical Functioning domain scores using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

Secondary: Change from Baseline in On-Treatment Physical Functioning domain scores using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

Secondary: Change from Baseline in On-Treatment Health Utility EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Questionnaire Score at Week 52

Secondary: Change from Baseline in On-Treatment Health Utility EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Questionnaire Score at Week 52

Secondary: Change from Baseline in On-Treatment EuroQol Visual Analogue Scale (EQ-VAS) at Week 52

Secondary: Change from Baseline in On-Treatment EuroQol Visual Analogue Scale (EQ-VAS) at Week 52

Secondary: Change from Baseline in On-Treatment Patient Global Impression of Severity (PGI-S) at Weeks 8, 12, 28, 52