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    Clinical Trial Results:
    A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Study of the Safety and Efficacy of Roxadustat in the Treatment of Anemia in Dialysis Patients

    Summary
    EudraCT number
    		 2014-000780-40
    Trial protocol
    		 SE   CZ   SK   HU   ES   BG   PL  
    Global end of trial date
    26 Sep 2018

    Results information
    Results version number
    		 v2
    This version publication date
    31 Oct 2019
    First version publication date
    12 Oct 2019
    Other versions
    		 v1 , v3
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    D5740C00002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02174731
    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
    26 Sep 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Sep 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 for the treatment of anemia in chronic kidney disease (CKD) participants 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
    01 Jul 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
    Australia: 34
    Country: Number of subjects enrolled
    Bulgaria: 139
    Country: Number of subjects enrolled
    Canada: 55
    Country: Number of subjects enrolled
    Czech Republic: 26
    Country: Number of subjects enrolled
    Hungary: 63
    Country: Number of subjects enrolled
    India: 86
    Country: Number of subjects enrolled
    Mexico: 109
    Country: Number of subjects enrolled
    Peru: 76
    Country: Number of subjects enrolled
    Philippines: 85
    Country: Number of subjects enrolled
    Poland: 49
    Country: Number of subjects enrolled
    Russian Federation: 91
    Country: Number of subjects enrolled
    Slovakia: 32
    Country: Number of subjects enrolled
    Spain: 39
    Country: Number of subjects enrolled
    Sweden: 9
    Country: Number of subjects enrolled
    Thailand: 45
    Country: Number of subjects enrolled
    Ukraine: 240
    Country: Number of subjects enrolled
    United States: 776
    Country: Number of subjects enrolled
    Vietnam: 152
    Worldwide total number of subjects
    2106
    EEA total number of subjects
    357
    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)
    1581
    From 65 to 84 years
    501
    85 years and over
    24

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study was conducted at 197 centers in 18 countries worldwide across the United States (US), Canada, Latin America, Australia, Asia and Europe between 01 July 2014 and 26 September 2018. Participants with CKD who were 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). 2133 participants were randomized, of which 2106 were included in the analysis and 27 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
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Roxadustat
    Arm description
    		 Participants received roxadustat tablets orally three times a week (TIW) throughout the treatment period (up to 4 years). For hemodialysis (HD) participants, it was recommended that roxadustat was taken after completion of the HD session. For participants treated with an erythropoietin analogue at study entry, selection of initial roxadustat dose was based on the participant’s erythropoietin analogue dose at screening Visit 1. Participants not treated with an erythropoietin analogue at study entry initiated roxadustat using a tiered, weight-based dosing scheme. Doses were titrated to achieve and maintain hemoglobin (Hb) values of 11±1 grams per deciliter (g/dL). Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks using a dose adjustment algorithm.
    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
    Roxadustat tablets orally TIW throughout the treatment period (up to 4 years). Doses were titrated to achieve and maintain Hb values of 11±1 g/dL.

    Arm title
    		 Epoetin alfa
    Arm description
    		 Participants received epoetin alfa (only use of Procrit®, Eprex® and Epogen® permitted in the study) subcutaneous (SC) or intravenous (IV) injection TIW, except for participants treated with epoetin alfa in a less frequent regimen prior to study entry. For participants treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was the actual dose administered at screening Visit 1. Participants treated with darbepoetin alfa or methoxy polyethylene glycol-epoetin beta prior to study entry initially received epoetin alfa at doses based on a conversion factor. For participants not treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was 50 international unit per kilogram (IU/kg) TIW. Dose adjustments were to be consistent with local approved prescribing information.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Eprex®
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use, Intravenous use
    Dosage and administration details
    Eprex® injections TIW throughout the treatment period (up to 4 years). Dose adjustments were to be consistent with local approved prescribing information.

    Investigational medicinal product name
    Procrit®
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use, Intravenous use
    Dosage and administration details
    Procrit® injections TIW throughout the treatment period (up to 4 years). Dose adjustments were to be consistent with local approved prescribing information.

    Investigational medicinal product name
    Epogen®
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use, Intravenous use
    Dosage and administration details
    Epogen® injections TIW throughout the treatment period (up to 4 years). Dose adjustments were to be consistent with local approved prescribing information.

    Number of subjects in period 1
    		Roxadustat Epoetin alfa
    Started
    1051
    1055
    Received treatment
    1048
    1053
    Completed
    982
    990
    Not completed
    69
    65
         Incorrect enrolment before randomization
    -
    1
         Participant decision
    67
    64
         Missing
    2
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Roxadustat
    Reporting group description
    		 Participants received roxadustat tablets orally three times a week (TIW) throughout the treatment period (up to 4 years). For hemodialysis (HD) participants, it was recommended that roxadustat was taken after completion of the HD session. For participants treated with an erythropoietin analogue at study entry, selection of initial roxadustat dose was based on the participant’s erythropoietin analogue dose at screening Visit 1. Participants not treated with an erythropoietin analogue at study entry initiated roxadustat using a tiered, weight-based dosing scheme. Doses were titrated to achieve and maintain hemoglobin (Hb) values of 11±1 grams per deciliter (g/dL). Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks using a dose adjustment algorithm.

    Reporting group title
    Epoetin alfa
    Reporting group description
    		 Participants received epoetin alfa (only use of Procrit®, Eprex® and Epogen® permitted in the study) subcutaneous (SC) or intravenous (IV) injection TIW, except for participants treated with epoetin alfa in a less frequent regimen prior to study entry. For participants treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was the actual dose administered at screening Visit 1. Participants treated with darbepoetin alfa or methoxy polyethylene glycol-epoetin beta prior to study entry initially received epoetin alfa at doses based on a conversion factor. For participants not treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was 50 international unit per kilogram (IU/kg) TIW. Dose adjustments were to be consistent with local approved prescribing information.

    Reporting group values
    		 Roxadustat Epoetin alfa Total
    Number of subjects
    		 1051 1055 2106
    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)
    		 798 783 1581
        From 65-84 years
    		 241 260 501
        85 years and over
    		 12 12 24
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 53.5 ( 15.30 ) 54.5 ( 14.97 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 426 429 855
        Male
    		 625 626 1251
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 597 598 1195
        Black of African American
    		 148 158 306
        Asian
    		 208 198 406
        Native Hawaiian or other Pacific Islander
    		 5 3 8
        American Indian or Alaska Native
    		 50 62 112
        Other
    		 43 36 79
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 268 271 539
        Not Hispanic or Latino
    		 783 784 1567
        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 three times a week (TIW) throughout the treatment period (up to 4 years). For hemodialysis (HD) participants, it was recommended that roxadustat was taken after completion of the HD session. For participants treated with an erythropoietin analogue at study entry, selection of initial roxadustat dose was based on the participant’s erythropoietin analogue dose at screening Visit 1. Participants not treated with an erythropoietin analogue at study entry initiated roxadustat using a tiered, weight-based dosing scheme. Doses were titrated to achieve and maintain hemoglobin (Hb) values of 11±1 grams per deciliter (g/dL). Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks using a dose adjustment algorithm.

    Reporting group title
    Epoetin alfa
    Reporting group description
    		 Participants received epoetin alfa (only use of Procrit®, Eprex® and Epogen® permitted in the study) subcutaneous (SC) or intravenous (IV) injection TIW, except for participants treated with epoetin alfa in a less frequent regimen prior to study entry. For participants treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was the actual dose administered at screening Visit 1. Participants treated with darbepoetin alfa or methoxy polyethylene glycol-epoetin beta prior to study entry initially received epoetin alfa at doses based on a conversion factor. For participants not treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was 50 international unit per kilogram (IU/kg) TIW. Dose adjustments were to be consistent with local approved prescribing information.

    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 three last central laboratory Hb values from the screening and randomization visits. Mean change in Hb from baseline to the participants mean level from Week 28 to Week 52 was analyzed using a missing at random (MAR) based multiple imputation analysis of covariance (ANCOVA). Baseline Hb was used as a covariate and treatment group, cardiovascular (CV) history, geographic region and dialysis duration as fixed effects. The adjusted least squares (LS) mean estimates of change from baseline 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), Week 28 to 52
    End point values
    		 Roxadustat Epoetin alfa
    Number of subjects analysed
    1003
    1016
    Units: g/dL
        least squares mean (standard error)
    0.77 ( 0.041 )
    0.68 ( 0.040 )
    Statistical analysis title
    		 Treatment Difference in Hb
    Comparison groups
    Epoetin alfa v Roxadustat
    Number of subjects included in analysis
    2019
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.01
         upper limit
    		 0.18
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.044
    Notes
    [1] - Non-inferiority of roxadustat versus epoetin alfa was declared if the lower bound of the 95% confidence interval (CI) of the difference between roxadustat and epoetin alfa exceeded -0.75. Non-inferiority p-value is 1-sided. Difference between groups (roxadustat minus Epoetin alfa) in LS mean changes.

    Primary: European Union (EU) Health Authorities Analysis: Change in Hb From Baseline to the Mean Level During the Evaluation Period (Week 28 to Week 36) Without Having Received Rescue Therapy Within 6 Weeks Prior to and During the 8‑Week Evaluation Period

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    End point title
    		 European Union (EU) Health Authorities Analysis: Change in Hb From Baseline to the Mean Level During the Evaluation Period (Week 28 to Week 36) Without Having Received Rescue Therapy Within 6 Weeks Prior to and During the 8‑Week Evaluation Period
    End point description
    Baseline Hb was defined as mean of three last central laboratory Hb values from screening and randomization visits. Mean change in Hb from baseline to participants mean level from Week 28 to 36, without having received rescue therapy within 6 weeks prior to and during this 8-week evaluation period was analysed using Mixed Model of Repeated Measures (MMRM). Baseline Hb was used as a covariate and treatment group, CV history, geographic region and dialysis duration as fixed effects. Adjusted LS mean estimates of change from baseline during Week 28 to Week 36 are presented for participants that did not receive rescue therapy within 6 weeks prior to and during this 8 week evaluation period. Per Protocol Set (PPS) included all randomized participants without important protocol deviations who had received at least 8 weeks of study treatment and had valid corresponding Hb measurements. Participants from PPS, with data available for analysis are presented.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Week 0), Week 28 to 36
    End point values
    		 Roxadustat Epoetin alfa
    Number of subjects analysed
    836
    864
    Units: g/dL
        least squares mean (standard error)
    0.88 ( 0.044 )
    0.74 ( 0.043 )
    Statistical analysis title
    		 Treatment Difference in Hb
    Comparison groups
    Roxadustat v Epoetin alfa
    Number of subjects included in analysis
    1700
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    P-value
    		 < 0.001
    Method
    		 MMRM
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.03
         upper limit
    		 0.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.056
    Notes
    [2] - Non-inferiority of roxadustat versus epoetin alfa was declared if the lower bound of the 95% CI of the difference between roxadustat and epoetin alfa exceeded -0.75. Non-inferiority p-value is 1-sided. Difference between groups (roxadustat minus Epoetin alfa) in LS mean change.

    Secondary: Proportion of Total Time of Hb Within the Interval of >=10 g/dL From Week 28 to Week 52

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    End point title
    		 Proportion of Total Time of Hb Within the Interval of >=10 g/dL From Week 28 to Week 52
    End point description
    The proportion of total time was computed as follows: For each participant, the recorded Hb values were first linearly interpolated between measurements. The time this interpolated curve was >=10 g/dL was computed and subsequently divided by the time between the measurements from Week 28 to Week 52. The difference between roxadustat and epoetin alfa were compared using ANCOVA. Baseline Hb was used as a covariate and the treatment groups, CV history, geographic region and dialysis duration as fixed effects. 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 to 52
    End point values
    		 Roxadustat Epoetin alfa
    Number of subjects analysed
    896
    941
    Units: proportion of total time
        least squares mean (standard error)
    0.79 ( 0.012 )
    0.76 ( 0.012 )
    Statistical analysis title
    		 Treatment Difference in Total Time of Hb
    Comparison groups
    Roxadustat v Epoetin alfa
    Number of subjects included in analysis
    1837
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [3]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0.05
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.013
    Notes
    [3] - Non-inferiority of roxadustat versus epoetin alfa was declared if the lower bound of the 95% CI of the difference between roxadustat and epoetin alfa exceeded -0.15. Non-inferiority p-value is 1-sided. Difference between groups (roxadustat minus Epoetin alfa) in LS mean.

    Secondary: Proportion of Total Time of Hb 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 Hb Within the Interval of 10 to 12 g/dL From Week 28 to Week 52
    End point description
    The proportion of total time was computed as follows: For each participant, the recorded Hb values were first linearly interpolated between measurements. The time this interpolated curve was within 10-12 g/dL was computed and subsequently divided by the time between the measurement from Week 28 to 52. The difference between roxadustat and epoetin alfa were compared using ANCOVA. Baseline Hb was used as a covariate and the treatment groups, CV history, geographic region and dialysis duration as fixed effects. 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 to 52
    End point values
    		 Roxadustat Epoetin alfa
    Number of subjects analysed
    896
    941
    Units: proportion of total time
        least squares mean (standard error)
    0.65 ( 0.013 )
    0.63 ( 0.012 )
    Statistical analysis title
    		 Treatment Difference in Total Time of Hb
    Comparison groups
    Roxadustat v Epoetin alfa
    Number of subjects included in analysis
    1837
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [4]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.01
         upper limit
    		 0.05
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.014
    Notes
    [4] - Non-inferiority of roxadustat versus epoetin alfa was declared if the lower bound of the 95% CI of the difference between roxadustat and epoetin alfa exceeded -0.15. Non-inferiority p-value is 1-sided. Difference between groups (roxadustat minus Epoetin alfa) in LS mean.

    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 analysed using ANCOVA. Baseline Hb and baseline LDL were used as covariates and treatment groups, CV history, geographic region and dialysis duration 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) to Week 24
    End point values
    		 Roxadustat Epoetin alfa
    Number of subjects analysed
    902
    937
    Units: millimole per liter
        least squares mean (standard error)
    -0.38 ( 0.026 )
    -0.05 ( 0.026 )
    Statistical analysis title
    		 Treatment Difference in LDL Cholesterol
    Comparison groups
    Roxadustat v Epoetin alfa
    Number of subjects included in analysis
    1839
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.39
         upper limit
    		 -0.27
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.03
    Notes
    [5] - Superiority was also declared as the lower bound of the 95% CI exceeded 0 and p-value was lower than 0.05. Difference between groups (roxadustat minus Epoetin alfa) in LS mean.

    Secondary: Mean Change in Hb From Baseline to the Participant’s Mean Level Between 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 in Hb From Baseline to the Participant’s Mean Level Between 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 is defined as the mean of the three last central laboratory Hb values from the screening and randomization visits. Changes in Hb from baseline to mean value during Weeks 28 to 52 in participants with baseline hsCRP >ULN was analyzed using a MAR based multiple imputation ANCOVA. Baseline Hb was used as a covariate and treatment group, CV history, geographic region and dialysis duration as fixed effects. The adjusted LS mean estimates of change from baseline 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), Week 28 to 52
    End point values
    		 Roxadustat Epoetin alfa
    Number of subjects analysed
    280
    301
    Units: g/dL
        least squares mean (standard error)
    0.80 ( 0.077 )
    0.59 ( 0.076 )
    Statistical analysis title
    		 Treatment Difference in Hb
    Comparison groups
    Roxadustat v Epoetin alfa
    Number of subjects included in analysis
    581
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [6]
    P-value
    		 < 0.001 [7]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.04
         upper limit
    		 0.36
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.081
    Notes
    [6] - Non-inferiority of roxadustat versus epoetin alfa was declared if the lower bound of the 95% CI of the difference between roxadustat and epoetin alfa exceeded -0.75. Non-inferiority p-value is 1-sided. Difference between groups (roxadustat minus Epoetin alfa) in LS mean.
    [7] - MAR-based multiple imputation.

    Secondary: Mean Monthly IV Iron Use From Week 36 to End of Study (EOS)

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    End point title
    		 Mean Monthly IV Iron Use From Week 36 to End of Study (EOS)
    End point description
    Oral iron supplementation was allowed for both treatment groups without restriction. Oral iron was recommended for dietary supplementation to support erythropoiesis and as the first line treatment for prevention and treatment of iron deficiency, unless the participant was intolerant to this route of treatment. In participants receiving roxadustat, the Investigator was allowed to initiate the use of an approved IV iron supplement if a participant’s Hb value had not sufficiently responded to 2 or more dose increases of the IP, and ferritin <100 nanogram per milliliter (ng/mL) or transferrin saturation (TSAT) <20%. IP treatment was allowed to continue during IV iron administration. Discontinuation of IV iron supplementation was recommended once the participant was no longer considered to be iron deficient (ferritin >100 ng/mL and TSAT >20%). Results for participants in ITT analysis set were presented.
    End point type
    Secondary
    End point timeframe
    Week 36 to EOS (4 weeks after the treatment period)
    End point values
    		 Roxadustat Epoetin alfa
    Number of subjects analysed
    885
    920
    Units: mg
        arithmetic mean (standard deviation)
    58.71 ( 236.12 )
    91.37 ( 225.64 )
    Statistical analysis title
    		 Treatment Difference in Iron use
    Comparison groups
    Roxadustat v Epoetin alfa
    Number of subjects included in analysis
    1805
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Wilcoxon Rank Sum Test
    Confidence interval

    Secondary: Time-To-First Administration of RBC Transfusion as Rescue Therapy

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    End point title
    		 Time-To-First Administration of RBC Transfusion as Rescue Therapy
    End point description
    Time-to-first RBC transfusion as rescue therapy was calculated as (date of first occurrence of any RBC transfusion as rescue therapy, or date of censoring if no event had occurred) - (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+3 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 3 days after the last administration of the IP.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Week 0) up to EOS (4 weeks after the treatment period)
    End point values
    		 Roxadustat Epoetin alfa
    Number of subjects analysed
    1048
    1053
    Units: event rate
        number (not applicable)
    6.0
    7.2
    Statistical analysis title
    		 Treatment Difference in RBC Transfusion
    Comparison groups
    Roxadustat v Epoetin alfa
    Number of subjects included in analysis
    2101
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [8]
    P-value
    		 < 0.001
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 1.07
    Notes
    [8] - Non-inferiority of roxadustat versus epoetin alfa was declared if the upper bound of the HR 95% CI of the difference between roxadustat and epoetin alfa was less than or equal to 1.8. Non-inferiority p-value is 1-sided. The CIs were from Wald and ties were calculated using the Efron method.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the first dose of IP administration (Day 1, Week 0) to 28 days after the last administration of the IP, with treatment duration up to 4 years.
    Adverse event reporting additional description
    The on-treatment+28 days safety analysis set included all participants who received at least 1 dose of randomized IP, except for those excluded from analysis. Participants were censored at 28 days after the last administration of the IP.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Epoetin alfa
    Reporting group description
    		 Participants received epoetin alfa (only use of Procrit®, Eprex® and Epogen® permitted in the study) SC or IV injection TIW, except for participants treated with epoetin alfa in a less frequent regimen prior to study entry. For participants treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was the actual dose administered at screening Visit 1. Participants treated with darbepoetin alfa or methoxy polyethylene glycol-epoetin beta prior to study entry initially received epoetin alfa at doses based on a conversion factor. For participants not treated with an erythropoietin analogue at study entry, the initial dose of epoetin alfa was 50 IU/kg TIW. Dose adjustments were to be consistent with local approved prescribing information.

    Reporting group title
    Roxadustat
    Reporting group description
    		 Participants received roxadustat tablets orally TIW throughout the treatment period (up to 4 years). For HD participants, it was recommended that roxadustat was taken after completion of the HD session. For participants treated with an erythropoietin analogue at study entry, selection of initial roxadustat dose was based on the participant’s erythropoietin analogue dose at screening Visit 1. Participants not treated with an erythropoietin analogue at study entry initiated roxadustat using a tiered, weight-based dosing scheme. Doses were titrated to achieve and maintain Hb values of 11±1 g/dL. Dose adjustments were permitted starting at Week 4 and at intervals of every 4 weeks using a dose adjustment algorithm.

    Serious adverse events
    		 Epoetin alfa Roxadustat
    Total subjects affected by serious adverse events
         subjects affected / exposed
    606 / 1053 (57.55%)
    604 / 1048 (57.63%)
         number of deaths (all causes)
    231
    247
         number of deaths resulting from adverse events
    187
    167
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    5q minus syndrome
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenocarcinoma
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         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
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adrenal neoplasm
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    B-cell lymphoma
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign neoplasm of thyroid gland
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer stage IV
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bladder neoplasm
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain neoplasm
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Breast cancer female
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer metastatic
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cervix carcinoma
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangiocarcinoma
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer metastatic
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Gastrointestinal carcinoma
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Gastrointestinal stromal tumour
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung carcinoma cell type unspecified stage IV
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lung neoplasm
         subjects affected / exposed
    3 / 1053 (0.28%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphoma
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Malignant pleural effusion
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to lung
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to peritoneum
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal carcinoma
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteochondroma
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Papillary thyroid cancer
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parathyroid tumour
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parathyroid tumour benign
         subjects affected / exposed
    1 / 1053 (0.09%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    1 / 1053 (0.09%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer recurrent
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal neoplasm
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal neoplasm
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin angiosarcoma
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin cancer
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Accelerated hypertension
         subjects affected / exposed
    6 / 1053 (0.57%)
    6 / 1048 (0.57%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic aneurysm
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    1 / 1053 (0.09%)
    4 / 1048 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial haemorrhage
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial occlusive disease
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Arteriosclerosis
         subjects affected / exposed
    1 / 1053 (0.09%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Bleeding varicose vein
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood pressure inadequately controlled
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brachiocephalic vein occlusion
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brachiocephalic vein stenosis
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brachiocephalic vein thrombosis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 1053 (0.00%)
    11 / 1048 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic microangiopathy
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dry gangrene
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Extremity necrosis
         subjects affected / exposed
    3 / 1053 (0.28%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    3 / 1053 (0.28%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    12 / 1053 (1.14%)
    12 / 1048 (1.15%)
         occurrences causally related to treatment / all
    0 / 13
    1 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    36 / 1053 (3.42%)
    24 / 1048 (2.29%)
         occurrences causally related to treatment / all
    1 / 38
    4 / 32
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    31 / 1053 (2.94%)
    24 / 1048 (2.29%)
         occurrences causally related to treatment / all
    1 / 33
    2 / 26
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hypotension
         subjects affected / exposed
    18 / 1053 (1.71%)
    17 / 1048 (1.62%)
         occurrences causally related to treatment / all
    0 / 20
    0 / 18
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Hypovolaemic shock
         subjects affected / exposed
    2 / 1053 (0.19%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Iliac artery occlusion
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemia
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jugular vein thrombosis
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant hypertension
         subjects affected / exposed
    2 / 1053 (0.19%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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
    3 / 1053 (0.28%)
    6 / 1048 (0.57%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery aneurysm
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    1 / 1053 (0.09%)
    4 / 1048 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery thrombosis
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    5 / 1053 (0.47%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral vascular disorder
         subjects affected / exposed
    6 / 1053 (0.57%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Phlebitis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock
         subjects affected / exposed
    1 / 1053 (0.09%)
    4 / 1048 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    3 / 1053 (0.28%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Steal syndrome
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subclavian vein thrombosis
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Superior vena cava stenosis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Superior vena cava syndrome
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombophlebitis superficial
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular compression
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vena cava thrombosis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous aneurysm
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous stenosis
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Adverse drug reaction
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    4 / 1053 (0.38%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter site haemorrhage
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    4 / 1053 (0.38%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Complication associated with device
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Complication of device insertion
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    23 / 1053 (2.18%)
    21 / 1048 (2.00%)
         occurrences causally related to treatment / all
    0 / 23
    0 / 21
         deaths causally related to treatment / all
    0 / 23
    0 / 21
    Device related thrombosis
         subjects affected / exposed
    1 / 1053 (0.09%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    General physical health deterioration
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Generalised oedema
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic cyst
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inflammation
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza like illness
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    4 / 1053 (0.38%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 4
    0 / 2
    Non-cardiac chest pain
         subjects affected / exposed
    9 / 1053 (0.85%)
    12 / 1048 (1.15%)
         occurrences causally related to treatment / all
    0 / 11
    1 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    8 / 1053 (0.76%)
    8 / 1048 (0.76%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    3 / 1053 (0.28%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 3
    0 / 3
    Sudden death
         subjects affected / exposed
    5 / 1053 (0.47%)
    6 / 1048 (0.57%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 5
    0 / 6
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    2 / 1053 (0.19%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contrast media allergy
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dialysis membrane reaction
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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 / 1053 (0.00%)
    1 / 1048 (0.10%)
         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
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transplant rejection
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metrorrhagia
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Varicocele
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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
    7 / 1053 (0.66%)
    6 / 1048 (0.57%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 6
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    Acute respiratory distress syndrome
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    9 / 1053 (0.85%)
    13 / 1048 (1.24%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 13
         deaths causally related to treatment / all
    0 / 3
    0 / 4
    Aspiration
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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
    2 / 1053 (0.19%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchiectasis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis chronic
         subjects affected / exposed
    2 / 1053 (0.19%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         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
    7 / 1053 (0.66%)
    6 / 1048 (0.57%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic respiratory failure
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    7 / 1053 (0.66%)
    9 / 1048 (0.86%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    2 / 1053 (0.19%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydrothorax
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    14 / 1053 (1.33%)
    15 / 1048 (1.43%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pleurisy
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    3 / 1053 (0.28%)
    7 / 1048 (0.67%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumothorax
         subjects affected / exposed
    3 / 1053 (0.28%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Productive cough
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary alveolar haemorrhage
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary artery thrombosis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary congestion
         subjects affected / exposed
    1 / 1053 (0.09%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    8 / 1053 (0.76%)
    6 / 1048 (0.57%)
         occurrences causally related to treatment / all
    1 / 8
    1 / 6
         deaths causally related to treatment / all
    1 / 3
    1 / 2
    Pulmonary fibrosis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    20 / 1053 (1.90%)
    10 / 1048 (0.95%)
         occurrences causally related to treatment / all
    0 / 22
    0 / 13
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Respiratory distress
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory failure
         subjects affected / exposed
    9 / 1053 (0.85%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 9
    1 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    Respiratory tract haemorrhage
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety disorder
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    1 / 1053 (0.09%)
    4 / 1048 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hallucination
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hallucination, visual
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Illusion
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         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
    6 / 1053 (0.57%)
    6 / 1048 (0.57%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Panic attack
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         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 / 1053 (0.09%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device failure
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device leakage
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device malfunction
         subjects affected / exposed
    3 / 1053 (0.28%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device occlusion
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombosis in device
         subjects affected / exposed
    1 / 1053 (0.09%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Anticoagulation drug level above therapeutic
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood potassium increased
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coagulation test abnormal
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Echocardiogram abnormal
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoglobin decreased
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Human rhinovirus test positive
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulse absent
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respirovirus test positive
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stress echocardiogram abnormal
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Synovial fluid crystal present
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anastomotic ulcer
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous fistula aneurysm
         subjects affected / exposed
    2 / 1053 (0.19%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous fistula occlusion
         subjects affected / exposed
    3 / 1053 (0.28%)
    4 / 1048 (0.38%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous fistula site complication
         subjects affected / exposed
    5 / 1053 (0.47%)
    9 / 1048 (0.86%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 10
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Arteriovenous fistula site haemorrhage
         subjects affected / exposed
    3 / 1053 (0.28%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous fistula thrombosis
         subjects affected / exposed
    31 / 1053 (2.94%)
    37 / 1048 (3.53%)
         occurrences causally related to treatment / all
    2 / 35
    4 / 46
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous graft aneurysm
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous graft site stenosis
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous graft thrombosis
         subjects affected / exposed
    10 / 1053 (0.95%)
    6 / 1048 (0.57%)
         occurrences causally related to treatment / all
    1 / 13
    1 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest injury
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Complications of transplanted kidney
         subjects affected / exposed
    1 / 1053 (0.09%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Craniofacial fracture
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Extradural haematoma
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    6 / 1053 (0.57%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    2 / 1053 (0.19%)
    4 / 1048 (0.38%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    6 / 1053 (0.57%)
    6 / 1048 (0.57%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    3 / 1053 (0.28%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Forearm fracture
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foreign body
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fracture displacement
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frostbite
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal stoma complication
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Graft thrombosis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemodialysis-induced symptom
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    6 / 1053 (0.57%)
    4 / 1048 (0.38%)
         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
    2 / 1053 (0.19%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint injury
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kidney rupture
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         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 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple fractures
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle rupture
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nerve root injury
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         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
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perirenal haematoma
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritoneal dialysis complication
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post concussion syndrome
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    4 / 1053 (0.38%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural urine leak
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound complication
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural haemorrhage
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pubis fracture
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    3 / 1053 (0.28%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shunt stenosis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shunt thrombosis
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    2 / 1053 (0.19%)
    4 / 1048 (0.38%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Subcutaneous haematoma
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    6 / 1053 (0.57%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Subdural haemorrhage
         subjects affected / exposed
    2 / 1053 (0.19%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Tendon injury
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic haematoma
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular access complication
         subjects affected / exposed
    2 / 1053 (0.19%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular access malfunction
         subjects affected / exposed
    4 / 1053 (0.38%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular access site occlusion
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular access site pseudoaneurysm
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular access site thrombosis
         subjects affected / exposed
    13 / 1053 (1.23%)
    16 / 1048 (1.53%)
         occurrences causally related to treatment / all
    1 / 15
    0 / 20
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular graft complication
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular graft occlusion
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular injury
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular pseudoaneurysm ruptured
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound necrosis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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
    Fibrous dysplasia of bone
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 1053 (0.09%)
    6 / 1048 (0.57%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Acute left ventricular failure
         subjects affected / exposed
    3 / 1053 (0.28%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Acute myocardial infarction
         subjects affected / exposed
    41 / 1053 (3.89%)
    39 / 1048 (3.72%)
         occurrences causally related to treatment / all
    0 / 46
    3 / 49
         deaths causally related to treatment / all
    0 / 9
    0 / 7
    Angina pectoris
         subjects affected / exposed
    8 / 1053 (0.76%)
    8 / 1048 (0.76%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    6 / 1053 (0.57%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    3 / 1053 (0.28%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 1053 (0.00%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    18 / 1053 (1.71%)
    10 / 1048 (0.95%)
         occurrences causally related to treatment / all
    0 / 21
    0 / 12
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial thrombosis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         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 / 1053 (0.00%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular dissociation
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    2 / 1053 (0.19%)
    6 / 1048 (0.57%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bundle branch block left
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    7 / 1053 (0.66%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 4
    0 / 2
    Cardiac asthma
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorder
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    10 / 1053 (0.95%)
    13 / 1048 (1.24%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 14
         deaths causally related to treatment / all
    0 / 5
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    5 / 1053 (0.47%)
    10 / 1048 (0.95%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 11
         deaths causally related to treatment / all
    0 / 1
    0 / 5
    Cardiac failure chronic
         subjects affected / exposed
    5 / 1053 (0.47%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    29 / 1053 (2.75%)
    24 / 1048 (2.29%)
         occurrences causally related to treatment / all
    0 / 43
    0 / 35
         deaths causally related to treatment / all
    0 / 3
    0 / 3
    Cardiac perforation
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac valve disease
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    4 / 1053 (0.38%)
    7 / 1048 (0.67%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 7
         deaths causally related to treatment / all
    0 / 3
    1 / 4
    Cardiogenic shock
         subjects affected / exposed
    2 / 1053 (0.19%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Cardiomegaly
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiopulmonary failure
         subjects affected / exposed
    4 / 1053 (0.38%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 3
    0 / 2
    Cardiovascular disorder
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiovascular insufficiency
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Congestive cardiomyopathy
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cor pulmonale acute
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Coronary artery disease
         subjects affected / exposed
    16 / 1053 (1.52%)
    17 / 1048 (1.62%)
         occurrences causally related to treatment / all
    0 / 18
    0 / 17
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Coronary artery stenosis
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive heart disease
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracardiac thrombus
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    6 / 1053 (0.57%)
    14 / 1048 (1.34%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 15
         deaths causally related to treatment / all
    0 / 2
    0 / 8
    Myocardial ischaemia
         subjects affected / exposed
    6 / 1053 (0.57%)
    4 / 1048 (0.38%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    Nodal arrhythmia
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericarditis uraemic
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulseless electrical activity
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    3 / 1053 (0.28%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         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
    4 / 1053 (0.38%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular extrasystoles
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachyarrhythmia
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia paroxysmal
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tricuspid valve disease
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Trifascicular block
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    4 / 1053 (0.38%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 4
    0 / 1
    Ventricular hypokinesia
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    4 / 1053 (0.38%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Nervous system disorders
    Aphasia
         subjects affected / exposed
    0 / 1053 (0.00%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ataxia
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal ganglia haemorrhage
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain hypoxia
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Brain injury
         subjects affected / exposed
    0 / 1053 (0.00%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Brain oedema
         subjects affected / exposed
    0 / 1053 (0.00%)
    4 / 1048 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    Brain stem stroke
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery aneurysm
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         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 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    2 / 1053 (0.19%)
    4 / 1048 (0.38%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Cerebral infarction
         subjects affected / exposed
    4 / 1053 (0.38%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral small vessel ischaemic disease
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    12 / 1053 (1.14%)
    14 / 1048 (1.34%)
         occurrences causally related to treatment / all
    0 / 12
    1 / 14
         deaths causally related to treatment / all
    0 / 5
    0 / 1
    Cerebrovascular insufficiency
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical cord compression
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coma
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         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 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Dizziness
         subjects affected / exposed
    2 / 1053 (0.19%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolic stroke
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    6 / 1053 (0.57%)
    8 / 1048 (0.76%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    2 / 1053 (0.19%)
    4 / 1048 (0.38%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Haemorrhagic stroke
         subjects affected / exposed
    6 / 1053 (0.57%)
    4 / 1048 (0.38%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 5
    0 / 2
    Headache
         subjects affected / exposed
    1 / 1053 (0.09%)
    4 / 1048 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive encephalopathy
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemic encephalopathy
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hypoxic-ischaemic encephalopathy
         subjects affected / exposed
    4 / 1053 (0.38%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracranial haematoma
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Ischaemic stroke
         subjects affected / exposed
    11 / 1053 (1.04%)
    10 / 1048 (0.95%)
         occurrences causally related to treatment / all
    0 / 12
    1 / 10
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Lacunar infarction
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lacunar stroke
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar radiculopathy
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    3 / 1053 (0.28%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myoclonus
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Partial seizures
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyneuropathy
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Posterior reversible encephalopathy syndrome
         subjects affected / exposed
    1 / 1053 (0.09%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postresuscitation encephalopathy
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatic nerve neuropathy
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    7 / 1053 (0.66%)
    13 / 1048 (1.24%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural hygroma
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    11 / 1053 (1.04%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    1 / 13
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tardive dyskinesia
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tonic convulsion
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxic encephalopathy
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    6 / 1053 (0.57%)
    10 / 1048 (0.95%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebral artery stenosis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo CNS origin
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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
    2 / 1053 (0.19%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Aplasia pure red cell
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone marrow failure
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone marrow reticulin fibrosis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemolytic anaemia
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic anaemia
         subjects affected / exposed
    3 / 1053 (0.28%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hilar lymphadenopathy
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenic infarction
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vestibular disorder
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Blindness unilateral
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic retinopathy
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye haemorrhage
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glaucoma
         subjects affected / exposed
    3 / 1053 (0.28%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal artery embolism
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal haemorrhage
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal vein occlusion
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulcerative keratitis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal adhesions
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    10 / 1053 (0.95%)
    10 / 1048 (0.95%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 1053 (0.00%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal wall haematoma
         subjects affected / exposed
    3 / 1053 (0.28%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal wall mass
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute abdomen
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic gastritis
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    3 / 1053 (0.28%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 1053 (0.00%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dental caries
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic gastroparesis
         subjects affected / exposed
    2 / 1053 (0.19%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    7 / 1053 (0.66%)
    4 / 1048 (0.38%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticular perforation
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal haemorrhagic
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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
    2 / 1053 (0.19%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    1 / 1053 (0.09%)
    4 / 1048 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer perforation
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenitis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis haemorrhagic
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocutaneous fistula
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erosive duodenitis
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Faeces discoloured
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Flatulence
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Food poisoning
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric disorder
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         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
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Gastric ulcer
         subjects affected / exposed
    2 / 1053 (0.19%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    5 / 1053 (0.47%)
    11 / 1048 (1.05%)
         occurrences causally related to treatment / all
    0 / 5
    1 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    4 / 1053 (0.38%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis haemorrhagic
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroduodenitis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal erosion
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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
    21 / 1053 (1.99%)
    22 / 1048 (2.10%)
         occurrences causally related to treatment / all
    0 / 25
    1 / 24
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Gastrointestinal perforation
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Gastrointestinal polyp haemorrhage
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 1053 (0.09%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    3 / 1053 (0.28%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic erosive gastritis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    4 / 1053 (0.38%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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 / 1053 (0.09%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired gastric emptying
         subjects affected / exposed
    4 / 1053 (0.38%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incarcerated inguinal hernia
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inflammatory bowel disease
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 1053 (0.09%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal haemorrhage
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal metaplasia
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    2 / 1053 (0.19%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intra-abdominal haemorrhage
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    2 / 1053 (0.19%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Malabsorption
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Mallory-Weiss syndrome
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal motility disorder
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    1 / 1053 (0.09%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic disorder
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic necrosis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 1053 (0.09%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    5 / 1053 (0.47%)
    6 / 1048 (0.57%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    Pancreatitis chronic
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic ulcer
         subjects affected / exposed
    2 / 1053 (0.19%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic ulcer haemorrhage
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Proctitis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal ulcer
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retroperitoneal haematoma
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    8 / 1053 (0.76%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 9
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         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
    9 / 1053 (0.85%)
    8 / 1048 (0.76%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 8
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Vomiting
         subjects affected / exposed
    5 / 1053 (0.47%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary colic
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary dyskinesia
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    4 / 1053 (0.38%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    6 / 1053 (0.57%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 1053 (0.00%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cirrhosis
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis cholestatic
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis toxic
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disease
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jaundice
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         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 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Decubitus ulcer
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic foot
         subjects affected / exposed
    3 / 1053 (0.28%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic ulcer
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug reaction with eosinophilia and systemic symptoms
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ecchymosis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pruritus
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Red man syndrome
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    6 / 1053 (0.57%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stevens-Johnson syndrome
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxic epidermal necrolysis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         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
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Azotaemia
         subjects affected / exposed
    11 / 1053 (1.04%)
    13 / 1048 (1.24%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 15
         deaths causally related to treatment / all
    0 / 1
    0 / 5
    Calculus urinary
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    1 / 1053 (0.09%)
    7 / 1048 (0.67%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 7
    Cystitis haemorrhagic
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Dysuria
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    End stage renal disease
         subjects affected / exposed
    1 / 1053 (0.09%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 4
    Glomerulonephritis chronic
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Haematuria
         subjects affected / exposed
    4 / 1053 (0.38%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cyst
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cyst haemorrhage
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cyst ruptured
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    4 / 1053 (0.38%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Renal haematoma
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Tubulointerstitial nephritis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Hyperparathyroidism
         subjects affected / exposed
    1 / 1053 (0.09%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperparathyroidism secondary
         subjects affected / exposed
    2 / 1053 (0.19%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperparathyroidism tertiary
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypothyroidism
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    2 / 1053 (0.19%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calcification of muscle
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical spinal stenosis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Costochondritis
         subjects affected / exposed
    4 / 1053 (0.38%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint effusion
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mobility decreased
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle haemorrhage
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle spasms
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    3 / 1053 (0.28%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    4 / 1053 (0.38%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 1053 (0.09%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuropathic arthropathy
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteitis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteitis deformans
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteochondritis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteochondrosis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Soft tissue necrosis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal ligament ossification
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         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
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal sepsis
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess jaw
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         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
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess neck
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess of salivary gland
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess soft tissue
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute endocarditis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    3 / 1053 (0.28%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerotic gangrene
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous fistula site infection
         subjects affected / exposed
    3 / 1053 (0.28%)
    6 / 1048 (0.57%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous graft site infection
         subjects affected / exposed
    1 / 1053 (0.09%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    3 / 1053 (0.28%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis infective
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    2 / 1053 (0.19%)
    4 / 1048 (0.38%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial colitis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial infection
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial pyelonephritis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    1 / 1053 (0.09%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteriuria
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Balanoposthitis infective
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone tuberculosis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    5 / 1053 (0.47%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Campylobacter colitis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Candida pneumonia
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter site abscess
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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
    1 / 1053 (0.09%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    16 / 1053 (1.52%)
    12 / 1048 (1.15%)
         occurrences causally related to treatment / all
    0 / 18
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis of male external genital organ
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis infective
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic hepatitis C
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic tonsillitis
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Citrobacter sepsis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium bacteraemia
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         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
    3 / 1053 (0.28%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    3 / 1053 (0.28%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 1053 (0.00%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    11 / 1053 (1.04%)
    11 / 1048 (1.05%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    7 / 1053 (0.66%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic foot infection
         subjects affected / exposed
    2 / 1053 (0.19%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic gangrene
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea infectious
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    2 / 1053 (0.19%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Endocarditis bacterial
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endophthalmitis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterococcal sepsis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    2 / 1053 (0.19%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fungal infection
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         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 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fungal sepsis
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    11 / 1053 (1.04%)
    9 / 1048 (0.86%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gas gangrene
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    6 / 1053 (0.57%)
    11 / 1048 (1.05%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis aeromonas
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis bacterial
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         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
    3 / 1053 (0.28%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal bacterial infection
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    2 / 1053 (0.19%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal viral infection
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Graft infection
         subjects affected / exposed
    1 / 1053 (0.09%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HIV infection
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis B
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis C
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster infection neurological
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Implant site cellulitis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incision site abscess
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected cyst
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected fistula
         subjects affected / exposed
    1 / 1053 (0.09%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected seroma
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective exacerbation of bronchiectasis
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    2 / 1053 (0.19%)
    5 / 1048 (0.48%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    3 / 1053 (0.28%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint abscess
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Labyrinthitis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    3 / 1053 (0.28%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection viral
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lyme disease
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metapneumovirus infection
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mycobacterium abscessus infection
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Necrotising fasciitis
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neurocysticercosis
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         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 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ophthalmic herpes zoster
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    10 / 1053 (0.95%)
    10 / 1048 (0.95%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis acute
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parainfluenzae virus infection
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parasitic gastroenteritis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraspinal abscess
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic abscess
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perineal abscess
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periorbital cellulitis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    24 / 1053 (2.28%)
    24 / 1048 (2.29%)
         occurrences causally related to treatment / all
    0 / 37
    0 / 28
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Peritonsillar abscess
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pilonidal cyst
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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
    78 / 1053 (7.41%)
    70 / 1048 (6.68%)
         occurrences causally related to treatment / all
    0 / 92
    1 / 80
         deaths causally related to treatment / all
    0 / 5
    0 / 4
    Pneumonia bacterial
         subjects affected / exposed
    3 / 1053 (0.28%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia staphylococcal
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia streptococcal
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    2 / 1053 (0.19%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    3 / 1053 (0.28%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis chronic
         subjects affected / exposed
    1 / 1053 (0.09%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyonephrosis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal abscess
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cyst infection
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    2 / 1053 (0.19%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    7 / 1053 (0.66%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retroperitoneal abscess
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    40 / 1053 (3.80%)
    40 / 1048 (3.82%)
         occurrences causally related to treatment / all
    0 / 46
    0 / 44
         deaths causally related to treatment / all
    0 / 12
    0 / 12
    Septic embolus
         subjects affected / exposed
    1 / 1053 (0.09%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Septic encephalopathy
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    13 / 1053 (1.23%)
    12 / 1048 (1.15%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 13
         deaths causally related to treatment / all
    0 / 9
    0 / 6
    Shunt infection
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 1053 (0.00%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal osteomyelitis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    3 / 1053 (0.28%)
    4 / 1048 (0.38%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Stenotrophomonas infection
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic viral infection
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tetanus
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tuberculosis
         subjects affected / exposed
    3 / 1053 (0.28%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 1053 (0.19%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    13 / 1053 (1.23%)
    8 / 1048 (0.76%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    3 / 1053 (0.28%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Varicella
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular access site infection
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    4 / 1053 (0.38%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral pericarditis
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vulval abscess
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vulval cellulitis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vulvovaginal candidiasis
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound abscess
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    3 / 1053 (0.28%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Adult failure to thrive
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (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
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 1053 (0.09%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    2 / 1053 (0.19%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    1 / 1053 (0.09%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    3 / 1053 (0.28%)
    7 / 1048 (0.67%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 10
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Diabetic metabolic decompensation
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         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
    29 / 1053 (2.75%)
    32 / 1048 (3.05%)
         occurrences causally related to treatment / all
    0 / 35
    0 / 55
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Fluid retention
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    2 / 1053 (0.19%)
    8 / 1048 (0.76%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemic hyperosmolar nonketotic syndrome
         subjects affected / exposed
    0 / 1053 (0.00%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    21 / 1053 (1.99%)
    27 / 1048 (2.58%)
         occurrences causally related to treatment / all
    0 / 26
    0 / 32
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Hyperphosphataemia
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypervolaemia
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    2 / 1053 (0.19%)
    2 / 1048 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    11 / 1053 (1.04%)
    19 / 1048 (1.81%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 22
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    2 / 1053 (0.19%)
    3 / 1048 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    4 / 1053 (0.38%)
    0 / 1048 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    Type 1 diabetes mellitus
         subjects affected / exposed
    1 / 1053 (0.09%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 1053 (0.00%)
    1 / 1048 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Epoetin alfa Roxadustat
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    799 / 1053 (75.88%)
    826 / 1048 (78.82%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    85 / 1053 (8.07%)
    85 / 1048 (8.11%)
         occurrences all number
    124
    130
    Hypotension
         subjects affected / exposed
    54 / 1053 (5.13%)
    64 / 1048 (6.11%)
         occurrences all number
    83
    79
    Nervous system disorders
    Headache
         subjects affected / exposed
    56 / 1053 (5.32%)
    79 / 1048 (7.54%)
         occurrences all number
    85
    91
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    101 / 1053 (9.59%)
    114 / 1048 (10.88%)
         occurrences all number
    153
    159
    Nausea
         subjects affected / exposed
    65 / 1053 (6.17%)
    61 / 1048 (5.82%)
         occurrences all number
    94
    72
    Vomiting
         subjects affected / exposed
    52 / 1053 (4.94%)
    60 / 1048 (5.73%)
         occurrences all number
    64
    69
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    62 / 1053 (5.89%)
    61 / 1048 (5.82%)
         occurrences all number
    76
    77
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    61 / 1053 (5.79%)
    43 / 1048 (4.10%)
         occurrences all number
    95
    67
    Upper respiratory tract infection
         subjects affected / exposed
    54 / 1053 (5.13%)
    70 / 1048 (6.68%)
         occurrences all number
    77
    102

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Sep 2014
    Roxadustat dosing and dose adjustment: 120 mg start dose, and 120 mg and 350 mg dose steps removed. Roxadustat dosing algorithm: 0.8 changed to 1.0. Single dose adjustment algorithm used throughout treatment period. Dose cap reduced from lower of 3.5 mg/kg or 400 mg to 3.0 mg/kg or 400 mg. Definition of excessive erythropoiesis simplified. Visit 1 changed to a phone call. Removed visits at Week 3, 5, and 7. Visits every 4 weeks after Week 52. Visit window from ±2 days to -4 days to 2 days. Inclusion criteria #5 and #6: Ferritin raised to ≥100 ng/mL and transferrin saturation raised to ≥20%. Exclusion criteria #3 deleted, #9 changed from Bosniak category II to IIF, #10 added definition of uncontrolled hypertension in dialysis subjects, and #13 added “that is determined to be principal cause of anemia”. Replaced statins text: “When coadministered with roxadustat, hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) exposure was increased 2- to 3-fold. Investigators should consider this interaction and local prescribing information when deciding on appropriate statin dose for individual participants, bearing in mind impact of ethnicity, other concomitant medications, renal and hepatic function. Recommended maximum daily statin doses are: simvastatin 20 mg, atorvastatin 40 mg, rosuvastatin 10 mg, pravastatin 40 mg, fluvastatin 40 mg (20 mg if estimated glomerular filtration rate (eGFR) <30), pitavastatin 2 mg (1 mg if eGFR <30.)”. Euro quality of life health utility index continued every 24 weeks after Week 52 and added at next visit after composite safety endpoint (CSE) event. Removed annual study discontinuation rate of 8.5% and changed estimated time to 1.4 years instead of 1.5 years. Study center number changed from 400 to approximately 250. Priority of secondary objectives changed: rescue therapy placed before self reported health status. Changed ANCOVA to MMRM for efficacy analysis. “Recombinant erythropoietin” replaced with “erythropoietin analogue”.
    19 Sep 2018
    Previous primary efficacy objective and its outcome measures is designated for US FDA. A second outcome measure designated for the EU health authority (Hb change from baseline to average Hb of Weeks 28 to 36, without having received rescue therapy within 6 weeks prior to and during this 8-week evaluation period) was added. Added that hepcidin and hsCRP were to be analyzed from biomarker samples. Full Analysis Set: renamed as “ITT Analysis Set”, and text revised to clarify how event of interest will be counted in respect of IP discontinuation according to ITT principle. “Patients” changed to “subjects” throughout corresponding protocol section (Section 8). Per Protocol Set: an additional criterion was added (“participants receiving at least 8 weeks of study treatment”), censoring rules for participants with an important protocol deviation were clarified, and the treatment groups to which PPS participants belong were specified. Full Analysis Set: section newly created allowing for an additional analysis set. Participants who will not be included in any analysis set: section newly created to specify participants not included in any analysis set, and their reason for exclusion. Primary efficacy endpoint text changed as follows: A new subsection with 2 parts, one for the US FDA and other for the EU health authority was created. Secondary efficacy endpoints changed as follows: Endpoint for time to first RBC transfusion or erythropoiesis stimulating agent as rescue therapy was changed to exploratory endpoint. Additional endpoints related to Hb response, lipid reduction, RBC rescue therapy use, and IV iron use were added. Primary safety objective/additional safety composite endpoints changed as follows: A new section entitled “Adjudicated CV Events Analyses for Safety Assessments” was created. Time to event analyses including time to first major adverse CV events+, time to first CSE, and time to first rescue therapy (composite) were removed.

    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.
    27 participants were excluded from the analysis due to GCP violations or system technical issues (17 in the roxadustat group and 10 in the epoetin alfa 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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