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    Clinical Trial Results:
    A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Roxadustat for the Treatment of Anemia in Chronic Kidney Disease Patients not on Dialysis

    Summary
    EudraCT number
    		 2014-000770-19
    Trial protocol
    		 CZ   SK   HU   DE   ES   BG   PL   RO  
    Global end of trial date
    04 Oct 2018

    Results information
    Results version number
    		 v2(current)
    This version publication date
    15 Jan 2020
    First version publication date
    31 Oct 2019
    Other versions
    		 v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    D5740C00001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02174627
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca
    Sponsor organisation address
    101 Orchard Ridge Drive, Gaithersburg, Maryland, United States, 20878
    Public contact
    Global Clinical Lead, AstraZeneca, +1 302 885 1180, ClinicalTrialTransparency@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca, +1 302 885 1180, ClinicalTrialTransparency@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    04 Oct 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Oct 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy and safety of roxadustat compared with placebo for the treatment of anemia in chronic kidney disease (CKD) participants not on dialysis.
    Protection of trial subjects
    This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with International Council for Harmonisation/Good Clinical Practice (GCP), applicable regulatory requirements, and the AstraZeneca policy on Bioethics and Human Biological Sample.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    26 Jun 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 74
    Country: Number of subjects enrolled
    Brazil: 85
    Country: Number of subjects enrolled
    Bulgaria: 78
    Country: Number of subjects enrolled
    Canada: 50
    Country: Number of subjects enrolled
    Colombia: 4
    Country: Number of subjects enrolled
    Czech Republic: 20
    Country: Number of subjects enrolled
    Germany: 5
    Country: Number of subjects enrolled
    Hungary: 50
    Country: Number of subjects enrolled
    India: 205
    Country: Number of subjects enrolled
    Korea, Republic of: 245
    Country: Number of subjects enrolled
    Malaysia: 15
    Country: Number of subjects enrolled
    Mexico: 101
    Country: Number of subjects enrolled
    Peru: 147
    Country: Number of subjects enrolled
    Philippines: 97
    Country: Number of subjects enrolled
    Poland: 38
    Country: Number of subjects enrolled
    Romania: 3
    Country: Number of subjects enrolled
    Russian Federation: 102
    Country: Number of subjects enrolled
    Slovakia: 9
    Country: Number of subjects enrolled
    Spain: 15
    Country: Number of subjects enrolled
    Taiwan: 129
    Country: Number of subjects enrolled
    Thailand: 89
    Country: Number of subjects enrolled
    Turkey: 32
    Country: Number of subjects enrolled
    Ukraine: 222
    Country: Number of subjects enrolled
    United States: 683
    Country: Number of subjects enrolled
    Vietnam: 263
    Worldwide total number of subjects
    2761
    EEA total number of subjects
    218
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    1526
    From 65 to 84 years
    1137
    85 years and over
    98

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study was conducted at 385 centers in 25 countries worldwide across the United States (US), Canada, Latin America, Asia and Europe between 26 June 2014 and 04 October 2018. Participants with CKD who were not on dialysis were recruited in this study.

    Pre-assignment
    Screening details
    		 Study had a screening period (up to 6 weeks), treatment period (up to 4 years) and follow-up period (4 weeks after treatment period for those who completed treatment). 2781 participants were randomized, of which 2761 were included in the analysis and 20 were excluded. Only participants included in the analysis are presented in the participant flow.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Roxadustat
    Arm description
    		 Participants received roxadustat tablets orally times a week (TIW). The initial dose was 70 milligrams (mg) TIW and was titrated to achieve and maintain haemoglobin (Hb) 11±1 grams per deciliter (g/dL). Treatment started on Day 1 and treatment duration was variable for individual participants (estimated up to 4 years). Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks until Week 52, every 8 weeks thereafter using a dose adjustment algorithm; all dose adjustments were based on Hb values.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Roxadustat
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The initial dose was 70 mg orally TIW. Dosing continued TIW throughout the treatment period (up to 4 years) unless downward dose adjustment required a change to twice or once weekly.

    Arm title
    		 Placebo
    Arm description
    		 Participants received treatment with placebo tablets orally TIW. Dosing instructions were matched to instructions provided for roxadustat (ie, initial dose matched 70 mg TIW). Treatment started on Day 1 and treatment duration was variable for individual participants (estimated up to 4 years). Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks until Week 52, every 8 weeks thereafter using a dose adjustment algorithm; all dose adjustments were based on Hb values.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo tablets matched to size and strength of roxadustat tablets, orally TIW. Dosing continued TIW throughout the treatment period (up to 4 years) unless downward dose adjustment required a change to twice or once weekly.

    Number of subjects in period 1
    		Roxadustat Placebo
    Started
    1384
    1377
    Received treatment
    1384
    1376
    Discontinued treatment
    499 [1]
    801 [2]
    Completed
    1300
    1247
    Not completed
    84
    130
         Incorrect enrolment before randomization
    -
    1
         Consent withdrawn by subject
    84
    128
         Missing
    -
    1
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Either resolve this issue or provide a justification.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Either resolve this issue or provide a justification.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Roxadustat
    Reporting group description
    		 Participants received roxadustat tablets orally times a week (TIW). The initial dose was 70 milligrams (mg) TIW and was titrated to achieve and maintain haemoglobin (Hb) 11±1 grams per deciliter (g/dL). Treatment started on Day 1 and treatment duration was variable for individual participants (estimated up to 4 years). Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks until Week 52, every 8 weeks thereafter using a dose adjustment algorithm; all dose adjustments were based on Hb values.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received treatment with placebo tablets orally TIW. Dosing instructions were matched to instructions provided for roxadustat (ie, initial dose matched 70 mg TIW). Treatment started on Day 1 and treatment duration was variable for individual participants (estimated up to 4 years). Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks until Week 52, every 8 weeks thereafter using a dose adjustment algorithm; all dose adjustments were based on Hb values.

    Reporting group values
    		 Roxadustat Placebo Total
    Number of subjects
    		 1384 1377 2761
    Age categorical
    Units: Subjects
        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)
    		 796 730 1526
        From 65-84 years
    		 547 590 1137
        85 years and over
    		 41 57 98
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 60.9 ( 14.67 ) 62.4 ( 14.14 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 820 774 1594
        Male
    		 564 603 1167
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 623 611 1234
        Black or African American
    		 112 115 227
        Asian
    		 544 538 1082
        Native Hawaiian or other Pacific Islander
    		 0 2 2
        American Indian or Alaska Native
    		 24 29 53
        Other
    		 81 82 163
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 344 357 701
        Not Hispanic or Latino
    		 1040 1020 2060
        Unknown or Not Reported
    		 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Roxadustat
    Reporting group description
    		 Participants received roxadustat tablets orally times a week (TIW). The initial dose was 70 milligrams (mg) TIW and was titrated to achieve and maintain haemoglobin (Hb) 11±1 grams per deciliter (g/dL). Treatment started on Day 1 and treatment duration was variable for individual participants (estimated up to 4 years). Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks until Week 52, every 8 weeks thereafter using a dose adjustment algorithm; all dose adjustments were based on Hb values.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received treatment with placebo tablets orally TIW. Dosing instructions were matched to instructions provided for roxadustat (ie, initial dose matched 70 mg TIW). Treatment started on Day 1 and treatment duration was variable for individual participants (estimated up to 4 years). Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks until Week 52, every 8 weeks thereafter using a dose adjustment algorithm; all dose adjustments were based on Hb values.

    Primary: US Food and Drug Administration (FDA) Analysis: Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52

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    End point title
    		 US Food and Drug Administration (FDA) Analysis: Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52
    End point description
    Baseline Hb was defined as the mean of the last 3 central laboratory Hb values from the screening and randomization visits. Mean change in Hb from baseline to mean value from Week 28 to Week 52 was analyzed using a missing at random (MAR) based multiple imputation analysis of covariance (ANCOVA) model with baseline Hb, baseline estimated glomerular filtration rate (eGFR), cardiovascular (CV) history, geographic region and treatment group as fixed effect covariates. The adjusted least squares (LS) mean estimates of change from baseline to mean during Week 28 to Week 52 are presented. The Intention-To-Treat (ITT) analysis set included all participants who were randomized to investigational product (IP) irrespective of their protocol adherence and continued participation in the study, except for those excluded from analysis.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Week 0) and Week 28 to Week 52.
    End point values
    		 Roxadustat Placebo
    Number of subjects analysed
    1334
    1330
    Units: g/dL
        least squares mean (standard error)
    1.75 ( 0.033 )
    0.40 ( 0.034 )
    Statistical analysis title
    		 Treatment Difference in Hb
    Statistical analysis description
    Difference between groups (roxadustat minus placebo) in LS mean changes; MAR-based multiple imputation ANCOVA model.
    Comparison groups
    Roxadustat v Placebo
    Number of subjects included in analysis
    2664
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    1.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.27
         upper limit
    		 1.43
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.041
    Notes
    [1] - Superiority of roxadustat compared with placebo would be declared if the lower bound of the 2-sided 95% confidence interval (CI) of the difference between roxadustat and placebo exceeded 0 g/dL.

    Primary: European Union (EU) Health Authorities Analysis: Percentage of Participants With Hb Response During the First 24 Weeks of Treatment

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    End point title
    		 European Union (EU) Health Authorities Analysis: Percentage of Participants With Hb Response During the First 24 Weeks of Treatment
    End point description
    Hb response was defined as: - Hb ≥ 11.0 g/dL and Hb increase from baseline by ≥ 1.0 g/dL for participants with baseline Hb > 8.0 g/dL; or - Hb increase from baseline by ≥ 2.0 g/dL, for participants with baseline Hb ≤ 8.0 g/dL at 2 consecutive visits (with available data) separated at least 5 days during the first 24 weeks of treatment without having received rescue therapy (red blood cell [RBC] transfusion, erythropoietin analogue, or intravenous [IV] iron) prior to Hb response. The percentage of participants with an Hb response during the first 24 weeks of treatment is presented. The Full Analysis Set (FAS) included all participants in the ITT analysis set who received at least 1 dose of IP and had baseline Hb and at least 1 post-dose Hb assessment. Participants from the FAS, with data available for analysis are presented.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Week 0) up to Week 24.
    End point values
    		 Roxadustat Placebo
    Number of subjects analysed
    1371
    1357
    Units: Percentage of participants
        number (not applicable)
    77.0
    8.5
    Statistical analysis title
    		 Treatment difference in Hb responders
    Statistical analysis description
    Comparison of the percentage of responders for roxadustat versus placebo was analysed using a Cochran-Mantel-Haenszel test adjusting for baseline Hb, baseline eGFR, geographic region and CV history.
    Comparison groups
    Roxadustat v Placebo
    Number of subjects included in analysis
    2728
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Relative Risk
    Point estimate
    9.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.63
         upper limit
    		 10.89

    Secondary: Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52 in Participants With Baseline High Sensitivity C-Reactive Protein (hsCRP) Greater Than the Upper Limit of Normal (ULN)

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    End point title
    		 Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52 in Participants With Baseline High Sensitivity C-Reactive Protein (hsCRP) Greater Than the Upper Limit of Normal (ULN)
    End point description
    Baseline hsCRP was quantified from stored biomarker samples obtained at randomization. Baseline Hb was defined as the mean of the last 3 central laboratory Hb values from the screening and randomization visits. Mean change in Hb from baseline to mean value during Week 28 to Week 52 was analyzed using a MAR based multiple imputation ANCOVA model with baseline Hb, baseline eGFR, CV history, geographic region and treatment group as fixed effect covariates. The adjusted LS mean estimates of change from baseline in participants with baseline hsCRP >ULN to mean during Week 28 to Week 52 are presented. The ITT analysis set included all participants who were randomized to IP irrespective of their protocol adherence and continued participation in the study, except for those excluded from analysis. Only participants who consented to the use of donated biomarker samples and had baseline hsCRP >ULN were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Week 0) and Week 28 to Week 52.
    End point values
    		 Roxadustat Placebo
    Number of subjects analysed
    213
    198
    Units: g/dL
        least squares mean (standard error)
    1.75 ( 0.087 )
    0.62 ( 0.091 )
    Statistical analysis title
    		 Treatment Difference in Hb
    Statistical analysis description
    Difference between groups (roxadustat minus placebo) in LS mean changes; MAR-based multiple imputation ANCOVA model.
    Comparison groups
    Roxadustat v Placebo
    Number of subjects included in analysis
    411
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    1.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.91
         upper limit
    		 1.35
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.112
    Notes
    [2] - Superiority of roxadustat compared with placebo would be declared if the lower bound of the 2-sided 95% CI of the difference between roxadustat and placebo exceeded 0 g/dL.

    Secondary: Proportion of Total Time of Interpolated Hb Values Greater Than or Equal To 10 g/dL From Week 28 to Week 52

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    End point title
    		 Proportion of Total Time of Interpolated Hb Values Greater Than or Equal To 10 g/dL From Week 28 to Week 52
    End point description
    Proportion of total time of interpolated Hb values ≥10 g/dL was calculated as the time the linearly interpolated curve between measurements ≥10 g/dL divided by the time between measurements from Week 28 to Week 52. Proportion of total time was analyzed using an ANCOVA model with baseline Hb and baseline eGFR as covariates, and CV history, geographic region and treatment group as fixed effects. The adjusted LS mean estimates of change from Week 28 to Week 52 are presented. The ITT analysis set included all participants who were randomized to IP irrespective of their protocol adherence and continued participation in the study, except for those excluded from analysis. Participants without any Hb measurements from Week 28 were not included in the analysis.
    End point type
    Secondary
    End point timeframe
    Week 28 up to Week 52.
    End point values
    		 Roxadustat Placebo
    Number of subjects analysed
    1220
    1145
    Units: proportion of total time
        least squares mean (standard error)
    0.82 ( 0.011 )
    0.33 ( 0.011 )
    Statistical analysis title
    		 Treatment Difference in Total Time of Hb
    Statistical analysis description
    Difference between groups (roxadustat minus placebo) in LS mean changes; ANCOVA model.
    Comparison groups
    Roxadustat v Placebo
    Number of subjects included in analysis
    2365
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 0.52
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.013
    Notes
    [3] - Superiority of roxadustat compared with placebo would be declared if the lower bound of the 2-sided 95% CI of the difference between roxadustat and placebo exceeded 0.

    Secondary: Proportion of Total Time of Interpolated Hb Values Within the Interval of 10 to 12 g/dL From Week 28 to Week 52

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    End point title
    		 Proportion of Total Time of Interpolated Hb Values Within the Interval of 10 to 12 g/dL From Week 28 to Week 52
    End point description
    Proportion of total time of interpolated Hb values within the interval of 10 to 12 g/dL was calculated as the time the linearly interpolated curve between measurements were within 10 to 12 g/dL divided by the time between measurements from Week 28 to Week 52. Proportion of total time was analyzed using an ANCOVA model with baseline Hb and baseline eGFR as covariates, and CV history, geographic region and treatment group as fixed effects. The adjusted LS mean estimates of change from Week 28 to Week 52 are presented. The ITT analysis set included all participants who were randomized to IP irrespective of their protocol adherence and continued participation in the study, except for those excluded from analysis. Participants without any Hb measurements from Week 28 were not included in the analysis.
    End point type
    Secondary
    End point timeframe
    Week 28 up to Week 52.
    End point values
    		 Roxadustat Placebo
    Number of subjects analysed
    1220
    1145
    Units: proportion of total time
        least squares mean (standard error)
    0.70 ( 0.010 )
    0.28 ( 0.010 )
    Statistical analysis title
    		 Treatment Difference in Total Time of Hb
    Statistical analysis description
    Difference between groups (roxadustat minus placebo) in LS mean changes; ANCOVA model.
    Comparison groups
    Roxadustat v Placebo
    Number of subjects included in analysis
    2365
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [4]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.4
         upper limit
    		 0.45
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.013
    Notes
    [4] - Superiority of roxadustat compared with placebo would be declared if the lower bound of the 2-sided 95% CI of the difference between roxadustat and placebo exceeded 0.

    Secondary: Mean Change in Low-Density Lipoprotein (LDL) Cholesterol From Baseline to Week 24

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    End point title
    		 Mean Change in Low-Density Lipoprotein (LDL) Cholesterol From Baseline to Week 24
    End point description
    Baseline LDL was defined as the last result obtained prior to randomization. Mean changes in LDL cholesterol from baseline to Week 24 was analyzed using an ANCOVA model with baseline LDL, baseline Hb and baseline eGFR as covariates, and CV history, geographic region and treatment group as fixed effects. The adjusted LS mean estimates of change from baseline to Week 24 are presented. The ITT analysis set included all participants who were randomized to IP irrespective of their protocol adherence and continued participation in the study, except for those excluded from analysis.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Week 0) and Week 24
    End point values
    		 Roxadustat Placebo
    Number of subjects analysed
    1147
    1133
    Units: millimole per liter
        least squares mean (standard error)
    -0.38 ( 0.028 )
    -0.02 ( 0.027 )
    Statistical analysis title
    		 Treatment Difference in LDL Cholesterol
    Statistical analysis description
    Difference between groups (roxadustat minus placebo) in LS mean changes; ANCOVA model.
    Comparison groups
    Roxadustat v Placebo
    Number of subjects included in analysis
    2280
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.42
         upper limit
    		 -0.29
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.033
    Notes
    [5] - Superiority of roxadustat compared with placebo would be declared if the lower bound of the 2-sided 95% CI of the difference between roxadustat and placebo exceeded 0.

    Secondary: Time-To-First Instance of Receiving IV Iron, RBC Transfusion or Erythropoietin Analogue as Rescue Therapy

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    End point title
    		 Time-To-First Instance of Receiving IV Iron, RBC Transfusion or Erythropoietin Analogue as Rescue Therapy
    End point description
    Time-to-first rescue therapy (IV iron, RBC transfusion or erythropoietin analogue) was calculated as (date of first rescue therapy, or date of censoring if no rescue therapy was taken) minus (date of first dose of IP) +1. Event rate was calculated as (number of participants with event) divided by (the total number of days at risk for event across all participants in given group divided by 365.25) multiplied by 100. The event rate is presented for participants with events. The on-treatment plus 28 days (OT+28) analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored 28 days after last intake of IP.
    End point type
    Secondary
    End point timeframe
    Baseline (Day1, Week 0) up to End of Study (EOS) visit (4 weeks after the treatment period) (or up to date of first rescue therapy), with treatment duration up to 4 years.
    End point values
    		 Roxadustat Placebo
    Number of subjects analysed
    1384
    1376
    Units: Events per 100 participant years
        number (not applicable)
    11.90
    39.76
    Statistical analysis title
    		 Treatment Difference in Rescue Therapy
    Statistical analysis description
    Treatments were compared using a Cox proportional hazards model, with baseline Hb and baseline eGFR as continuous variables used as covariates, and treatment group, CV history and geographic region as fixed effects. The Efron method was used for ties and p-values were calculated using the Wald test.
    Comparison groups
    Roxadustat v Placebo
    Number of subjects included in analysis
    2760
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [6]
    P-value
    		 < 0.001
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.23
         upper limit
    		 0.31
    Notes
    [6] - Superiority of roxadustat compared with placebo would be declared if the upper limit of the 2-sided 95% CI for the HR was ≤1.0.

    Secondary: Time-To-First Instance of Receiving a RBC Transfusion As Rescue Therapy

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    End point title
    		 Time-To-First Instance of Receiving a RBC Transfusion As Rescue Therapy
    End point description
    Time-to-first RBC rescue therapy was calculated as (date of first RBC rescue therapy, or date of censoring if no rescue therapy was taken) minus (date of first dose of IP) +1. Event rate was calculated as (number of participants with event) divided by (the total number of days at risk for event across all participants in given group divided by 365.25) multiplied by 100. The event rate is presented for participants with events. The OT+28 analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored 28 days after last intake of IP.
    End point type
    Secondary
    End point timeframe
    Baseline (Day1, Week 0) up to EOS visit (4 weeks after the treatment period) (or up to date of first RBC rescue therapy), with treatment duration up to 4 years.
    End point values
    		 Roxadustat Placebo
    Number of subjects analysed
    1384
    1376
    Units: Events per 100 participant years
        number (not applicable)
    7.98
    19.61
    Statistical analysis title
    		 Treatment Difference in RBC Transfusion
    Statistical analysis description
    Treatments were compared using a Cox proportional hazards model, with baseline Hb and baseline eGFR as continuous variables used as covariates, and treatment group, CV history and geographic region as fixed effects. The Efron method was used for ties and p-values were calculated using the Wald test.
    Comparison groups
    Roxadustat v Placebo
    Number of subjects included in analysis
    2760
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [7]
    P-value
    		 < 0.001
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.3
         upper limit
    		 0.44
    Notes
    [7] - Superiority of roxadustat compared with placebo would be declared if the upper limit of the 2-sided 95% CI for the HR was ≤1.0.

    Secondary: Mean Change From Baseline in Short Form 36 (SF-36) Vitality Sub-Score From Week 12 to Week 28

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    End point title
    		 Mean Change From Baseline in Short Form 36 (SF-36) Vitality Sub-Score From Week 12 to Week 28
    End point description
    SF-36 is a Quality of Life (QoL) scale comprising 8 domains of health status: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health. Each domain score is on a scale from 0-100 (worst health possible to best health possible); higher scores indicate better health status. Mean change in SF-36 Vitality sub-score from baseline to mean from Week 12 to Week 28 was analyzed using a mixed model for repeated measures (MMRM) with terms for baseline score, treatment group, baseline Hb, baseline eGFR, CV history, geographic region, visit and treatment-by-visit interaction as fixed effects and participant as random effect. The adjusted LS mean estimates of change from baseline to mean score from Week 12 to Week 28 are presented. The ITT analysis set included all participants who were randomized to IP irrespective of their protocol adherence and continued participation in the study, except for those excluded from analysis.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Week 0) and Week 12 to Week 28.
    End point values
    		 Roxadustat Placebo
    Number of subjects analysed
    1279
    1235
    Units: scores on a scale
        least squares mean (standard error)
    1.59 ( 0.231 )
    1.15 ( 0.233 )
    Statistical analysis title
    		 Treatment Difference in SF-36 Vitality
    Statistical analysis description
    Difference between groups (roxadustat minus placebo) in LS mean changes; MMRM analysis.
    Comparison groups
    Roxadustat v Placebo
    Number of subjects included in analysis
    2514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [8]
    P-value
    		 = 0.12
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.11
         upper limit
    		 0.99
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.283
    Notes
    [8] - Superiority of roxadustat compared with placebo would be declared if the lower bound of the 2-sided 95% CI of the difference between roxadustat and placebo exceeded 0.

    Secondary: Annual Rate of eGFR Change From Baseline Prior to the Initiation of Dialysis or Kidney Transplant

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    End point title
    		 Annual Rate of eGFR Change From Baseline Prior to the Initiation of Dialysis or Kidney Transplant
    End point description
    Baseline eGFR was defined as the mean of all available central laboratory values prior to or at randomization. Rate of change in eGFR from baseline during the entire treatment period (in milliliters/minute/1.73 meters squared/years [mL/min/1.73m^2/years]) was estimated using a random effects model using all post baseline eGFR values prior to initiation of dialysis/transplant. Baseline eGFR, baseline Hb, geographic region, CV history, treatment group and post baseline eGFR measurement time were used as fixed effects and participant and time (years) as random effects, ie, random intercept and slope. The ITT analysis set included all participants who were randomized to IP irrespective of their protocol adherence and continued participation in the study, except for those excluded from analysis.
    End point type
    Secondary
    End point timeframe
    Baseline (Day1, Week 0) up to EOS visit (4 weeks after the treatment period), with treatment duration up to 4 years.
    End point values
    		 Roxadustat Placebo
    Number of subjects analysed
    1326
    1314
    Units: eGFR rate (mL/min/1.73m^2/years)
        number (not applicable)
    -3.70
    -3.19
    Statistical analysis title
    		 Treatment Difference in eGFR Rate
    Statistical analysis description
    Difference between groups (roxadustat minus placebo) in rate of change in eGFR; random effects analysis.
    Comparison groups
    Roxadustat v Placebo
    Number of subjects included in analysis
    2640
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.046 [9]
    Method
    		 Random Effects Analysis
    Parameter type
    		 Rate of Change Difference
    Point estimate
    -0.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 -0.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.254
    Notes
    [9] - Nominal p-value (as prior sequential outcome measure p-value did not meet < 0.05.

    Secondary: Mean Change From Baseline in SF-36 Physical Functioning Sub-Score From Week 12 to Week 28

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    End point title
    		 Mean Change From Baseline in SF-36 Physical Functioning Sub-Score From Week 12 to Week 28
    End point description
    SF-36 is a QoL scale comprising 8 domains of health status: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional and Mental Health. Each domain score is on a scale from 0-100 (worst health possible to best health possible); higher scores indicate better health status. Mean change in SF-36 Physical Functioning sub-score from baseline to mean from Week 12 to Week 28 was analyzed using a MMRM with terms for baseline score, treatment group, baseline Hb, baseline eGFR, CV history, geographic region, visit and treatment-by-visit interaction as fixed effects and participant as random effect. The adjusted LS mean estimates of change from baseline to mean score from Week 12 to Week 28 are presented. The ITT analysis set included all participants who were randomized to IP irrespective of their protocol adherence and continued participation in the study, except for those excluded from analysis.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Week 0) and Week 12 to Week 28.
    End point values
    		 Roxadustat Placebo
    Number of subjects analysed
    1279
    1234
    Units: scores on a scale
        least squares mean (standard error)
    0.14 ( 0.222 )
    -0.39 ( 0.224 )
    Statistical analysis title
    		 Treatment Difference in SF-36 Physical Functioning
    Statistical analysis description
    Difference between groups (roxadustat minus placebo) in LS mean changes; MMRM analysis.
    Comparison groups
    Roxadustat v Placebo
    Number of subjects included in analysis
    2513
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [10]
    P-value
    		 = 0.051 [11]
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 1.05
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.269
    Notes
    [10] - Superiority of roxadustat compared with placebo would be declared if the lower bound of the 2-sided 95% CI of the difference between roxadustat and placebo exceeded 0.
    [11] - Nominal p-value (as prior sequential outcome measure p-value did not meet < 0.05.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From date of randomization up to EOS visit (4 weeks after the treatment period), with treatment duration up to 4 years.
    Adverse event reporting additional description
    The ITT analysis set included all participants who were randomized to IP irrespective of their protocol adherence and continued participation in the study, except for those excluded from analysis.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo tablets orally TIW. Dosing instructions were matched to instructions provided for roxadustat (ie, initial dose matched to 70 mg TIW). Treatment started on Day 1 and treatment duration was variable for individual participants (estimated up to 4 years). Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks until Week 52, every 8 weeks thereafter using a dose adjustment algorithm; all dose adjustments were based on Hb values.

    Reporting group title
    Roxadustat
    Reporting group description
    		 Participants received roxadustat tablets orally TIW. The initial dose was 70 mg TIW and was titrated to achieve and maintain Hb 11±1 g/dL. Treatment started on Day 1 and treatment duration was variable for individual participants (estimated up to 4 years). Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks until Week 52, every 8 weeks thereafter using a dose adjustment algorithm; all dose adjustments were based on Hb values.

    Serious adverse events
    		 Placebo Roxadustat
    Total subjects affected by serious adverse events
         subjects affected / exposed
    749 / 1377 (54.39%)
    795 / 1384 (57.44%)
         number of deaths (all causes)
    245
    284
         number of deaths resulting from adverse events
    213
    262
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (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
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer female
         subjects affected / exposed
    2 / 1377 (0.15%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer metastatic
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast neoplasm
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervix carcinoma
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon adenoma
         subjects affected / exposed
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon neoplasm
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colorectal cancer metastatic
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometrial cancer
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epiglottic carcinoma
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric adenoma
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric neoplasm
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal tract adenoma
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cancer
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngeal cancer
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leiomyoma
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lip squamous cell carcinoma
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung carcinoma cell type unspecified stage IV
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 1377 (0.07%)
    5 / 1384 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    Malignant melanoma
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (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 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelofibrosis
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasm of appendix
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuroendocrine tumour of the lung
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal carcinoma
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ovarian cancer
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    4 / 1377 (0.29%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Prostate cancer
         subjects affected / exposed
    0 / 1377 (0.00%)
    5 / 1384 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cancer
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Squamous cell carcinoma of skin
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (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 the vagina
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Accelerated hypertension
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic aneurysm
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic rupture
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic aneurysm rupture
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    4 / 1377 (0.29%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Arteriosclerosis
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Arteriovenous fistula
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (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
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    4 / 1377 (0.29%)
    15 / 1384 (1.08%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Distributive shock
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Dry gangrene
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolism venous
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Extremity necrosis
         subjects affected / exposed
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    4 / 1377 (0.29%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    16 / 1377 (1.16%)
    17 / 1384 (1.23%)
         occurrences causally related to treatment / all
    1 / 16
    0 / 19
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    27 / 1377 (1.96%)
    33 / 1384 (2.38%)
         occurrences causally related to treatment / all
    0 / 31
    0 / 51
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    21 / 1377 (1.53%)
    21 / 1384 (1.52%)
         occurrences causally related to treatment / all
    0 / 23
    0 / 24
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    8 / 1377 (0.58%)
    6 / 1384 (0.43%)
         occurrences causally related to treatment / all
    0 / 8
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    6 / 1377 (0.44%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    Iliac artery perforation
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jugular vein thrombosis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphocele
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant hypertension
         subjects affected / exposed
    1 / 1377 (0.07%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 1377 (0.07%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paget-Schroetter syndrome
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pallor
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    2 / 1377 (0.15%)
    5 / 1384 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Peripheral artery occlusion
         subjects affected / exposed
    3 / 1377 (0.22%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    1 / 1377 (0.07%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery thrombosis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    2 / 1377 (0.15%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral vascular disorder
         subjects affected / exposed
    1 / 1377 (0.07%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral venous disease
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post thrombotic syndrome
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    4 / 1377 (0.29%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    Steal syndrome
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subclavian artery thrombosis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (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
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombophlebitis superficial
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Varicose ulceration
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular occlusion
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Visceral congestion
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (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
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    9 / 1377 (0.65%)
    13 / 1384 (0.94%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter site haemorrhage
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter site pain
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    28 / 1377 (2.03%)
    43 / 1384 (3.11%)
         occurrences causally related to treatment / all
    1 / 28
    0 / 43
         deaths causally related to treatment / all
    1 / 28
    0 / 43
    Device related thrombosis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised oedema
         subjects affected / exposed
    7 / 1377 (0.51%)
    17 / 1384 (1.23%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 25
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hernia pain
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Implant site extravasation
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Implant site necrosis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inflammation
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (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 / 1377 (0.07%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 1377 (0.15%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    7 / 1377 (0.51%)
    7 / 1384 (0.51%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema due to renal disease
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    5 / 1377 (0.36%)
    7 / 1384 (0.51%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pacemaker generated arrhythmia
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral swelling
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    5 / 1377 (0.36%)
    6 / 1384 (0.43%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stenosis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Sudden death
         subjects affected / exposed
    11 / 1377 (0.80%)
    5 / 1384 (0.36%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 5
         deaths causally related to treatment / all
    0 / 11
    0 / 5
    Immune system disorders
    Anaphylactic shock
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device allergy
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kidney transplant rejection
         subjects affected / exposed
    1 / 1377 (0.07%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal transplant failure
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transplant rejection
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (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
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 1377 (0.07%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysfunctional uterine bleeding
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Menorrhagia
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cyst ruptured
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cyst torsion
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian mass
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic prolapse
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatic fibrosis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatic mass
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatomegaly
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (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 pulmonary oedema
         subjects affected / exposed
    22 / 1377 (1.60%)
    13 / 1384 (0.94%)
         occurrences causally related to treatment / all
    0 / 25
    0 / 13
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Acute respiratory distress syndrome
         subjects affected / exposed
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    20 / 1377 (1.45%)
    12 / 1384 (0.87%)
         occurrences causally related to treatment / all
    0 / 20
    0 / 13
         deaths causally related to treatment / all
    0 / 5
    0 / 5
    Aspiration
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Asthma
         subjects affected / exposed
    3 / 1377 (0.22%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial fistula
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis chronic
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    8 / 1377 (0.58%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Dyspnoea
         subjects affected / exposed
    12 / 1377 (0.87%)
    11 / 1384 (0.79%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Dyspnoea exertional
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    1 / 1377 (0.07%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Laryngeal stenosis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstructive airways disorder
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    16 / 1377 (1.16%)
    15 / 1384 (1.08%)
         occurrences causally related to treatment / all
    0 / 20
    0 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural thickening
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    1 / 1377 (0.07%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    2 / 1377 (0.15%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Pneumonitis
         subjects affected / exposed
    2 / 1377 (0.15%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 1377 (0.07%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary alveolar haemorrhage
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary congestion
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pulmonary embolism
         subjects affected / exposed
    3 / 1377 (0.22%)
    5 / 1384 (0.36%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pulmonary fibrosis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pulmonary haemorrhage
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pulmonary hypertension
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    16 / 1377 (1.16%)
    17 / 1384 (1.23%)
         occurrences causally related to treatment / all
    0 / 16
    0 / 17
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Respiratory alkalosis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    9 / 1377 (0.65%)
    5 / 1384 (0.36%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 5
         deaths causally related to treatment / all
    0 / 6
    0 / 2
    Tracheal stenosis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract inflammation
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Alcohol withdrawal syndrome
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bipolar disorder
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Confusional state
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    1 / 1377 (0.07%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Insomnia
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental disorder
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paranoia
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular cognitive impairment
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device dislocation
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device failure
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device malfunction
         subjects affected / exposed
    2 / 1377 (0.15%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stenosis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bile duct stone
         subjects affected / exposed
    1 / 1377 (0.07%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis acute
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 1377 (0.07%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 1377 (0.07%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic hepatic failure
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cirrhosis alcoholic
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Haemorrhagic hepatic cyst
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cirrhosis
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Hepatitis acute
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis alcoholic
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jaundice
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver disorder
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver injury
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Anticoagulation drug level increased
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood bicarbonate decreased
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatine increased
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood glucose abnormal
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood glucose increased
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood pressure decreased
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood pressure increased
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Blood urine present
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coagulation factor decreased
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Troponin increased
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Anastomotic stenosis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    1 / 1377 (0.07%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous fistula occlusion
         subjects affected / exposed
    4 / 1377 (0.29%)
    7 / 1384 (0.51%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous fistula site complication
         subjects affected / exposed
    4 / 1377 (0.29%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous fistula site haemorrhage
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous fistula thrombosis
         subjects affected / exposed
    9 / 1377 (0.65%)
    18 / 1384 (1.30%)
         occurrences causally related to treatment / all
    1 / 9
    1 / 19
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    0 / 1377 (0.00%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chemical peritonitis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chemical poisoning
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest injury
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Comminuted fracture
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Complications of transplanted kidney
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Compression fracture
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dialysis disequilibrium syndrome
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dialysis related complication
         subjects affected / exposed
    0 / 1377 (0.00%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    3 / 1377 (0.22%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    2 / 1377 (0.15%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (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
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fractured sacrum
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heat stroke
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    6 / 1377 (0.44%)
    5 / 1384 (0.36%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Joint dislocation
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint injury
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lip injury
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle injury
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periorbital haemorrhage
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritoneal dialysis complication
         subjects affected / exposed
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Post procedural complication
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural complication
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural haemorrhage
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural hypotension
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 1377 (0.07%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seroma
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shunt malfunction
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shunt occlusion
         subjects affected / exposed
    2 / 1377 (0.15%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin injury
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord injury cervical
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Spinal fracture
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spleen contusion
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stoma obstruction
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stoma site haemorrhage
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (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
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    2 / 1377 (0.15%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haemorrhage
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transplant dysfunction
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic liver injury
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (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 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular access malfunction
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular access site thrombosis
         subjects affected / exposed
    2 / 1377 (0.15%)
    6 / 1384 (0.43%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular graft complication
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular graft occlusion
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound haematoma
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (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
    Congenital cystic kidney disease
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydrocele
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    5 / 1377 (0.36%)
    8 / 1384 (0.58%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 8
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute left ventricular failure
         subjects affected / exposed
    4 / 1377 (0.29%)
    5 / 1384 (0.36%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Acute myocardial infarction
         subjects affected / exposed
    27 / 1377 (1.96%)
    26 / 1384 (1.88%)
         occurrences causally related to treatment / all
    1 / 31
    0 / 28
         deaths causally related to treatment / all
    0 / 6
    0 / 6
    Angina pectoris
         subjects affected / exposed
    9 / 1377 (0.65%)
    10 / 1384 (0.72%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    10 / 1377 (0.73%)
    10 / 1384 (0.72%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    3 / 1377 (0.22%)
    6 / 1384 (0.43%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    Aortic valve stenosis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    12 / 1377 (0.87%)
    10 / 1384 (0.72%)
         occurrences causally related to treatment / all
    1 / 15
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (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
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bundle branch block left
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    3 / 1377 (0.22%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    4 / 1377 (0.29%)
    9 / 1384 (0.65%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 3
    0 / 6
    Cardiac asthma
         subjects affected / exposed
    0 / 1377 (0.00%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    32 / 1377 (2.32%)
    25 / 1384 (1.81%)
         occurrences causally related to treatment / all
    0 / 35
    0 / 31
         deaths causally related to treatment / all
    0 / 5
    0 / 6
    Cardiac failure acute
         subjects affected / exposed
    14 / 1377 (1.02%)
    8 / 1384 (0.58%)
         occurrences causally related to treatment / all
    0 / 16
    0 / 8
         deaths causally related to treatment / all
    0 / 7
    0 / 3
    Cardiac failure chronic
         subjects affected / exposed
    5 / 1377 (0.36%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    31 / 1377 (2.25%)
    33 / 1384 (2.38%)
         occurrences causally related to treatment / all
    1 / 42
    0 / 41
         deaths causally related to treatment / all
    0 / 5
    0 / 7
    Cardiac tamponade
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    4 / 1377 (0.29%)
    6 / 1384 (0.43%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 3
    0 / 5
    Cardiogenic shock
         subjects affected / exposed
    1 / 1377 (0.07%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    Cardiomegaly
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    1 / 1377 (0.07%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiopulmonary failure
         subjects affected / exposed
    1 / 1377 (0.07%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    Chronic left ventricular failure
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congestive cardiomyopathy
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    7 / 1377 (0.51%)
    12 / 1384 (0.87%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Coronary artery insufficiency
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Coronary artery stenosis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heart valve incompetence
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heart valve stenosis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive cardiomyopathy
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Ischaemic cardiomyopathy
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Left ventricular failure
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular hypertrophy
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic cardiomyopathy
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve disease
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    13 / 1377 (0.94%)
    14 / 1384 (1.01%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 14
         deaths causally related to treatment / all
    0 / 9
    0 / 6
    Myocardial ischaemia
         subjects affected / exposed
    8 / 1377 (0.58%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 4
         deaths causally related to treatment / all
    0 / 4
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 1377 (0.00%)
    3 / 1384 (0.22%)
         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 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinoatrial block
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus arrest
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (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 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    3 / 1377 (0.22%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Nervous system disorders
    Aphasia
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Autonomic nervous system imbalance
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (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
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebellar infarction
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (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
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haematoma
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cerebral haemorrhage
         subjects affected / exposed
    3 / 1377 (0.22%)
    9 / 1384 (0.65%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 9
         deaths causally related to treatment / all
    0 / 3
    0 / 4
    Cerebral infarction
         subjects affected / exposed
    8 / 1377 (0.58%)
    13 / 1384 (0.94%)
         occurrences causally related to treatment / all
    1 / 9
    0 / 14
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    11 / 1377 (0.80%)
    15 / 1384 (1.08%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 15
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Cerebrovascular disorder
         subjects affected / exposed
    0 / 1377 (0.00%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cerebrovascular insufficiency
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical cord compression
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coma
         subjects affected / exposed
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Coma uraemic
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Dementia
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dementia Alzheimer's type
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Demyelination
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic hyperglycaemic coma
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic hyperosmolar coma
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic ketoacidotic hyperglycaemic coma
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Diabetic neuropathy
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    2 / 1377 (0.15%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 1377 (0.00%)
    5 / 1384 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial paralysis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial spasm
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    6 / 1377 (0.44%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 3
    0 / 2
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Headache
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    1 / 1377 (0.07%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive encephalopathy
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intercostal neuralgia
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic cerebral infarction
         subjects affected / exposed
    3 / 1377 (0.22%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    7 / 1377 (0.51%)
    9 / 1384 (0.65%)
         occurrences causally related to treatment / all
    0 / 7
    1 / 9
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Lacunar infarction
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lacunar stroke
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    3 / 1377 (0.22%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Myoclonus
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neurodegenerative disorder
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Neuroleptic malignant syndrome
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Neuropathy peripheral
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Occipital neuralgia
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraparesis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Partial seizures
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyneuropathy
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post stroke seizure
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (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 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    2 / 1377 (0.15%)
    6 / 1384 (0.43%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Senile dementia
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Somnolence
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    3 / 1377 (0.22%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thalamic infarction
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Thalamus haemorrhage
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Transient ischaemic attack
         subjects affected / exposed
    5 / 1377 (0.36%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uraemic encephalopathy
         subjects affected / exposed
    2 / 1377 (0.15%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    VIth nerve paralysis
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular encephalopathy
         subjects affected / exposed
    1 / 1377 (0.07%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebrobasilar insufficiency
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo CNS origin
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vestibular migraine
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (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
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coagulopathy
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Evans syndrome
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemolytic uraemic syndrome
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic anaemia
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Histiocytosis haematophagic
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypocoagulable state
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 1377 (0.07%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenitis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 1377 (0.07%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    3 / 1377 (0.22%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo positional
         subjects affected / exposed
    1 / 1377 (0.07%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vestibular ataxia
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vestibular disorder
         subjects affected / exposed
    1 / 1377 (0.07%)
    5 / 1384 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Blindness unilateral
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic retinopathy
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulcerative keratitis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Visual acuity reduced
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Visual impairment
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vitreous haemorrhage
         subjects affected / exposed
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal adhesions
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Abdominal discomfort
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    4 / 1377 (0.29%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal wall haematoma
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (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
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal incontinence
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 1377 (0.07%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic gastritis
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 1377 (0.07%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    1 / 1377 (0.07%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic gastroparesis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic gastropathy
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    5 / 1377 (0.36%)
    9 / 1384 (0.65%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dieulafoy's vascular malformation
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (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 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    1 / 1377 (0.07%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenitis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenitis haemorrhagic
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (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
    2 / 1377 (0.15%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis haemorrhagic
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erosive duodenitis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral hernia incarcerated
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Functional gastrointestinal disorder
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (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 / 1377 (0.00%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric polyps
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    2 / 1377 (0.15%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    3 / 1377 (0.22%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    15 / 1377 (1.09%)
    18 / 1384 (1.30%)
         occurrences causally related to treatment / all
    1 / 18
    0 / 24
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastritis haemorrhagic
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroduodenitis haemorrhagic
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorder
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    15 / 1377 (1.09%)
    20 / 1384 (1.45%)
         occurrences causally related to treatment / all
    0 / 16
    1 / 20
         deaths causally related to treatment / all
    0 / 0
    1 / 3
    Gastrointestinal inflammation
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic ascites
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (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
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileal perforation
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired gastric emptying
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incarcerated umbilical hernia
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    3 / 1377 (0.22%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia strangulated
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal haemorrhage
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    5 / 1377 (0.36%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mallory-Weiss syndrome
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mesenteric artery thrombosis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (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
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal ulcer
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal varices haemorrhage
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis ulcerative
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic cyst
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 1377 (0.00%)
    5 / 1384 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    4 / 1377 (0.29%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic ulcer
         subjects affected / exposed
    3 / 1377 (0.22%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic ulcer haemorrhage
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic ulcer perforation
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritoneal adhesions
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritoneal cloudy effluent
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritoneal haemorrhage
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumatosis intestinalis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal haemorrhage
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    4 / 1377 (0.29%)
    11 / 1384 (0.79%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 11
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Uraemic gastropathy
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 1377 (0.15%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Blister
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decubitus ulcer
         subjects affected / exposed
    0 / 1377 (0.00%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermatitis atopic
         subjects affected / exposed
    0 / 1377 (0.00%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic foot
         subjects affected / exposed
    5 / 1377 (0.36%)
    6 / 1384 (0.43%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Diabetic ulcer
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Papule
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Necrobiosis lipoidica diabeticorum
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    1 / 1377 (0.07%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxic epidermal necrolysis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stevens-Johnson syndrome
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (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
    Acute kidney injury
         subjects affected / exposed
    32 / 1377 (2.32%)
    41 / 1384 (2.96%)
         occurrences causally related to treatment / all
    0 / 33
    0 / 48
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Anuria
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Azotaemia
         subjects affected / exposed
    60 / 1377 (4.36%)
    61 / 1384 (4.41%)
         occurrences causally related to treatment / all
    0 / 79
    0 / 73
         deaths causally related to treatment / all
    0 / 10
    0 / 14
    Chronic kidney disease
         subjects affected / exposed
    7 / 1377 (0.51%)
    8 / 1384 (0.58%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 8
         deaths causally related to treatment / all
    0 / 5
    0 / 7
    Cystitis haemorrhagic
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic nephropathy
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    End stage renal disease
         subjects affected / exposed
    201 / 1377 (14.60%)
    199 / 1384 (14.38%)
         occurrences causally related to treatment / all
    0 / 211
    1 / 211
         deaths causally related to treatment / all
    0 / 11
    0 / 11
    Glomerulonephritis
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glomerulonephritis chronic
         subjects affected / exposed
    1 / 1377 (0.07%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Haematuria
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephritic syndrome
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephropathy toxic
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrotic syndrome
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstructive uropathy
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedematous kidney
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oliguria
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyuria
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelocaliectasis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal atrophy
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cyst
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cyst haemorrhage
         subjects affected / exposed
    3 / 1377 (0.22%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 1377 (0.07%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 1377 (0.07%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal pain
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal papillary necrosis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal pelvis fistula
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal tubular necrosis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tubulointerstitial nephritis
         subjects affected / exposed
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ureteric obstruction
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric stenosis
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary fistula
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 1377 (0.07%)
    5 / 1384 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract inflammation
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (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 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Goitre
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperparathyroidism
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperparathyroidism secondary
         subjects affected / exposed
    0 / 1377 (0.00%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical spinal stenosis
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (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
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gouty arthritis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemarthrosis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 1377 (0.07%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    2 / 1377 (0.15%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 1377 (0.07%)
    5 / 1384 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myositis
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    2 / 1377 (0.15%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 1377 (0.00%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    1 / 1377 (0.07%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    3 / 1377 (0.22%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spondylitis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic lupus erythematosus
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal infection
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    3 / 1377 (0.22%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute hepatitis B
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    5 / 1377 (0.36%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous fistula site infection
         subjects affected / exposed
    3 / 1377 (0.22%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous graft site infection
         subjects affected / exposed
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 1377 (0.07%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial infection
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone tuberculosis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    9 / 1377 (0.65%)
    7 / 1384 (0.51%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carbuncle
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac valve abscess
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter site cellulitis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter site infection
         subjects affected / exposed
    8 / 1377 (0.58%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    13 / 1377 (0.94%)
    24 / 1384 (1.73%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 27
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis gangrenous
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridial infection
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    2 / 1377 (0.15%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Clostridium difficile infection
         subjects affected / exposed
    2 / 1377 (0.15%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis bacterial
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus nephritis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    5 / 1377 (0.36%)
    14 / 1384 (1.01%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    5 / 1377 (0.36%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Diabetic foot infection
         subjects affected / exposed
    4 / 1377 (0.29%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic gangrene
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea infectious
         subjects affected / exposed
    4 / 1377 (0.29%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    3 / 1377 (0.22%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Emphysematous cystitis
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Emphysematous pyelonephritis
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    1 / 1377 (0.07%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocarditis bacterial
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endotoxic shock
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Enteritis infectious
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterobacter sepsis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterococcal sepsis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epiglottitis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fungaemia
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (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
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fungal peritonitis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Furuncle
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    7 / 1377 (0.51%)
    10 / 1384 (0.72%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    8 / 1377 (0.58%)
    13 / 1384 (0.94%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis bacterial
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 1377 (0.07%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    2 / 1377 (0.15%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    H1N1 influenza
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (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
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis B
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis B reactivation
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis C
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes virus infection
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected lymphocele
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected skin ulcer
         subjects affected / exposed
    0 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective aneurysm
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    5 / 1377 (0.36%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal tuberculosis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kidney infection
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella sepsis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Localised infection
         subjects affected / exposed
    5 / 1377 (0.36%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lung abscess
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    3 / 1377 (0.22%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymph node tuberculosis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasopharyngitis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (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 / 1377 (0.00%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    2 / 1377 (0.15%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis acute
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (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
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media chronic
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parvovirus infection
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perineal abscess
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perinephric abscess
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    14 / 1377 (1.02%)
    15 / 1384 (1.08%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Peritonitis bacterial
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonsillar abscess
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural infection
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    88 / 1377 (6.39%)
    113 / 1384 (8.16%)
         occurrences causally related to treatment / all
    1 / 107
    0 / 149
         deaths causally related to treatment / all
    0 / 10
    0 / 12
    Pneumonia bacterial
         subjects affected / exposed
    3 / 1377 (0.22%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Pneumonia influenzal
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia klebsiella
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia mycoplasmal
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural cellulitis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural pneumonia
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    2 / 1377 (0.15%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomembranous colitis
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomonas infection
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    2 / 1377 (0.15%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Purulence
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    5 / 1377 (0.36%)
    8 / 1384 (0.58%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    4 / 1377 (0.29%)
    6 / 1384 (0.43%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis chronic
         subjects affected / exposed
    11 / 1377 (0.80%)
    11 / 1384 (0.79%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pyoderma
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyonephrosis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cyst infection
         subjects affected / exposed
    1 / 1377 (0.07%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    23 / 1377 (1.67%)
    49 / 1384 (3.54%)
         occurrences causally related to treatment / all
    0 / 24
    0 / 51
         deaths causally related to treatment / all
    0 / 8
    0 / 26
    Septic shock
         subjects affected / exposed
    15 / 1377 (1.09%)
    18 / 1384 (1.30%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 19
         deaths causally related to treatment / all
    0 / 9
    0 / 14
    Sinusitis
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 1377 (0.00%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Staphylococcal sepsis
         subjects affected / exposed
    3 / 1377 (0.22%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stenotrophomonas sepsis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Streptococcal bacteraemia
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (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 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    4 / 1377 (0.29%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Taeniasis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tuberculosis
         subjects affected / exposed
    3 / 1377 (0.22%)
    5 / 1384 (0.36%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Typhoid fever
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    26 / 1377 (1.89%)
    36 / 1384 (2.60%)
         occurrences causally related to treatment / all
    0 / 32
    0 / 38
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Urinary tract infection bacterial
         subjects affected / exposed
    0 / 1377 (0.00%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    6 / 1377 (0.44%)
    8 / 1384 (0.58%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 11
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Vascular access site infection
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vestibular neuronitis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (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
    3 / 1377 (0.22%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Acidosis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adult failure to thrive
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calciphylaxis
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    2 / 1377 (0.15%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    4 / 1377 (0.29%)
    8 / 1384 (0.58%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Diabetes mellitus
         subjects affected / exposed
    3 / 1377 (0.22%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Diabetes mellitus inadequate control
         subjects affected / exposed
    3 / 1377 (0.22%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    10 / 1377 (0.73%)
    6 / 1384 (0.43%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 10
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Diabetic metabolic decompensation
         subjects affected / exposed
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Electrolyte imbalance
         subjects affected / exposed
    3 / 1377 (0.22%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fluid overload
         subjects affected / exposed
    22 / 1377 (1.60%)
    20 / 1384 (1.45%)
         occurrences causally related to treatment / all
    0 / 27
    0 / 28
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fluid retention
         subjects affected / exposed
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Food aversion
         subjects affected / exposed
    2 / 1377 (0.15%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    1 / 1377 (0.07%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    3 / 1377 (0.22%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    9 / 1377 (0.65%)
    16 / 1384 (1.16%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 17
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hyperglycaemic hyperosmolar nonketotic syndrome
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperinsulinaemic hypoglycaemia
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    25 / 1377 (1.82%)
    41 / 1384 (2.96%)
         occurrences causally related to treatment / all
    0 / 35
    2 / 53
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Hypernatraemia
         subjects affected / exposed
    0 / 1377 (0.00%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperuricaemia
         subjects affected / exposed
    2 / 1377 (0.15%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hypervolaemia
         subjects affected / exposed
    0 / 1377 (0.00%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    2 / 1377 (0.15%)
    2 / 1384 (0.14%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    26 / 1377 (1.89%)
    32 / 1384 (2.31%)
         occurrences causally related to treatment / all
    0 / 27
    0 / 38
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 1377 (0.07%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    6 / 1377 (0.44%)
    7 / 1384 (0.51%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 8
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Hypovolaemia
         subjects affected / exposed
    4 / 1377 (0.29%)
    3 / 1384 (0.22%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ketoacidosis
         subjects affected / exposed
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ketosis
         subjects affected / exposed
    1 / 1377 (0.07%)
    0 / 1384 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    4 / 1377 (0.29%)
    4 / 1384 (0.29%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    3 / 1377 (0.22%)
    7 / 1384 (0.51%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    Type 1 diabetes mellitus
         subjects affected / exposed
    2 / 1377 (0.15%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 1377 (0.07%)
    1 / 1384 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    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
    		 Placebo Roxadustat
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    757 / 1377 (54.97%)
    839 / 1384 (60.62%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    117 / 1377 (8.50%)
    148 / 1384 (10.69%)
         occurrences all number
    151
    190
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    86 / 1377 (6.25%)
    74 / 1384 (5.35%)
         occurrences all number
    113
    91
    Headache
         subjects affected / exposed
    82 / 1377 (5.95%)
    93 / 1384 (6.72%)
         occurrences all number
    96
    122
    General disorders and administration site conditions
    Oedema peripheral
         subjects affected / exposed
    106 / 1377 (7.70%)
    144 / 1384 (10.40%)
         occurrences all number
    135
    192
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    88 / 1377 (6.39%)
    91 / 1384 (6.58%)
         occurrences all number
    101
    126
    Diarrhoea
         subjects affected / exposed
    117 / 1377 (8.50%)
    138 / 1384 (9.97%)
         occurrences all number
    156
    190
    Nausea
         subjects affected / exposed
    103 / 1377 (7.48%)
    124 / 1384 (8.96%)
         occurrences all number
    127
    171
    Vomiting
         subjects affected / exposed
    67 / 1377 (4.87%)
    75 / 1384 (5.42%)
         occurrences all number
    85
    90
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    69 / 1377 (5.01%)
    105 / 1384 (7.59%)
         occurrences all number
    91
    123
    Dyspnoea
         subjects affected / exposed
    64 / 1377 (4.65%)
    70 / 1384 (5.06%)
         occurrences all number
    80
    85
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    80 / 1377 (5.81%)
    68 / 1384 (4.91%)
         occurrences all number
    89
    84
    Renal and urinary disorders
    End stage renal disease
         subjects affected / exposed
    85 / 1377 (6.17%)
    93 / 1384 (6.72%)
         occurrences all number
    86
    93
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    53 / 1377 (3.85%)
    73 / 1384 (5.27%)
         occurrences all number
    61
    85
    Back pain
         subjects affected / exposed
    57 / 1377 (4.14%)
    70 / 1384 (5.06%)
         occurrences all number
    69
    87
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    64 / 1377 (4.65%)
    72 / 1384 (5.20%)
         occurrences all number
    76
    80
    Upper respiratory tract infection
         subjects affected / exposed
    75 / 1377 (5.45%)
    95 / 1384 (6.86%)
         occurrences all number
    100
    137
    Urinary tract infection
         subjects affected / exposed
    94 / 1377 (6.83%)
    152 / 1384 (10.98%)
         occurrences all number
    135
    205
    Viral upper respiratory tract infection
         subjects affected / exposed
    106 / 1377 (7.70%)
    101 / 1384 (7.30%)
         occurrences all number
    152
    159
    Metabolism and nutrition disorders
    Hyperkalaemia
         subjects affected / exposed
    75 / 1377 (5.45%)
    86 / 1384 (6.21%)
         occurrences all number
    86
    105

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Sep 2014
    Tiered weight-based start doses changed to fixed 70 mg TIW start dose: 120 and 350 mg dose steps removed. Dose algorithm adjusted to reflect results of pharmacometric modeling and simulation using the simplified dosing regimen. Dose cap lowered as additional modeling/simulation indicated this dose would be sufficient. Definition of excessive erythropoiesis simplified. Visit 1 changed to a phone call. Removed visits at Weeks 3, 5, and 7. Visits every 8 weeks (not 4 weeks) after Week 52. Visit window from ±2 days to -4 days to 2 days. Priority order of secondary objectives changed. Rescue therapy objective prioritized before self-reported health status. Inclusion criteria: #3 reworded to clarify that qualifying eGFR was by central laboratory calculation; #5 and #6: Ferritin raised to ≥50 nanograms/mL and transferrin saturation raised to ≥15%. Exclusion criteria: #9 changed from Bosniak category II to IIF; #13 added “that is determined to be the principal cause of anemia”. Removed “or their guardian/legal representative” for participant consent. Deleted IP discontinuation for thrombocytopenia or bleeding. Rescue medication: IV iron guidance adjusted to align with guidelines. Added recommendation for oral iron supplementation. Inclusion of statins text to ask Investigators to consider roxadustat-statin interactions and local prescribing information when deciding on appropriate statin dose for individual participants. Inclusion of text on phosphate binders. Efficacy analysis set: Participants were not to be censored 96 hours after their last dose in the OT+28 population; ITT analysis set for major adverse cardiovascular event (MACE) instead. ANCOVA changed to MMRM for efficacy analysis. Added: “In subjects who do not experience a MACE event, the time-to-event will be censored at the EOT visit for analyses based both on the safety analysis population and on FAS”. Removed annual study discontinuation rate of 8.5% and changed estimated time from 1.5 years to 1.4 years.
    31 Aug 2018
    To harmonize D5740C00001 with other studies in the CKD-non-dialysis-dependent Phase 3 program, to serve as a pivotal study for confirming efficacy and safety and to facilitate assessment of pooled efficacy and safety data across the Phase 3 program, the following changes were implemented: Previous primary objective changed to primary safety objective (with CV safety analyses now being pooled across the study program). Addition of 2 primary efficacy objectives: one objective for the US FDA and one for the EU health authority. Previous primary objective text moved to new sub-section. Inclusion of text on pooled CV safety analyses and the pooled statistical analysis plan. Previous secondary objectives split out by objective type (efficacy and safety) and updated and new secondary objectives added. Study duration extended. Enrollment anticipated to occur over approximately a 3 year period. Text on sample size determination revised, including addition of text on sample size estimation for the primary efficacy objective. Study end date changed (extension of study into Q3 2018) to reflect a common end date across the Phase 3 studies when the required number of participants with adjudicated CV endpoints was anticipated. Additional criteria (participants requiring a third course of erythropoietin analogue rescue therapy, or those initiating dialysis who required erythropoietin analogue rescue therapy) for permanent discontinuation from the IP were added. Text added to state that hepcidin and hsCRP were to be analyzed from biomarker samples. Added definition of treatment emergent AE. FAS was renamed to the ITT and a new sub-section was added describing the new FAS. Changes were made to the criteria, treatment groups and censoring rules of the analysis sets. A new sub-section was added on participants who will not be included in any analysis set.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    20 participants were excluded from the analysis due to GCP violations or system technical issues (9 in the roxadustat group and 11 in the placebo group). Higher IP discontinuation was observed in placebo group versus in roxadustat group.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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