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    Clinical Trial Results:
    Multicenter, randomized, double-blind, double-dummy, active-comparator, event-driven, superiority phase III study of secondary prevention of stroke and prevention of systemic embolism in patients with a recent Embolic Stroke of Undetermined Source (ESUS), comparing rivaroxaban 15 mg once daily with aspirin 100 mg (NAVIGATE ESUS)

    Summary
    EudraCT number
    		 2013-000768-27
    Trial protocol
    		 SE   IE   PT   CZ   BE   ES   IT   HU   FI   DK   GB   AT   GR  
    Global end of trial date
    15 Feb 2018

    Results information
    Results version number
    		 v2(current)
    This version publication date
    03 Feb 2019
    First version publication date
    06 Dec 2018
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Update wording of the endpoints.

    Trial information

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    Trial identification
    Sponsor protocol code
    BAY59-7939/16573
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02313909
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bayer AG
    Sponsor organisation address
    Kaiser-Wilhelm-Allee, D-51368 Leverkusen, Germany,
    Public contact
    Therapeutic Area Head, Bayer AG , clinical-trials-contact@bayer.com
    Scientific contact
    Therapeutic Area Head, Bayer AG , clinical-trials-contact@bayer.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
    15 Feb 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Feb 2018
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary efficacy objective of this study was to evaluate whether rivaroxaban (Xarelto, BAY59-7939) was superior to acetylsalicylic acid (Aspirin) in reducing the risk of recurrent stroke and systemic embolism in subjects with a recent embolic stroke of undetermined source (ESUS).
    Protection of trial subjects
    The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Council for Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent form was read by and explained to all subjects. Participating subjects signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    23 Dec 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
    Poland: 284
    Country: Number of subjects enrolled
    Portugal: 154
    Country: Number of subjects enrolled
    Spain: 618
    Country: Number of subjects enrolled
    Sweden: 71
    Country: Number of subjects enrolled
    United Kingdom: 435
    Country: Number of subjects enrolled
    Austria: 174
    Country: Number of subjects enrolled
    Belgium: 90
    Country: Number of subjects enrolled
    Czech Republic: 243
    Country: Number of subjects enrolled
    Denmark: 146
    Country: Number of subjects enrolled
    Finland: 131
    Country: Number of subjects enrolled
    France: 288
    Country: Number of subjects enrolled
    Germany: 198
    Country: Number of subjects enrolled
    Greece: 76
    Country: Number of subjects enrolled
    Hungary: 224
    Country: Number of subjects enrolled
    Ireland: 13
    Country: Number of subjects enrolled
    Italy: 334
    Country: Number of subjects enrolled
    Australia: 119
    Country: Number of subjects enrolled
    Israel: 60
    Country: Number of subjects enrolled
    South Africa: 49
    Country: Number of subjects enrolled
    Switzerland: 125
    Country: Number of subjects enrolled
    Russian Federation: 328
    Country: Number of subjects enrolled
    Turkey: 39
    Country: Number of subjects enrolled
    China: 491
    Country: Number of subjects enrolled
    Japan: 647
    Country: Number of subjects enrolled
    Korea, Democratic People's Republic of: 212
    Country: Number of subjects enrolled
    Canada: 573
    Country: Number of subjects enrolled
    United States: 345
    Country: Number of subjects enrolled
    Argentina: 265
    Country: Number of subjects enrolled
    Brazil: 179
    Country: Number of subjects enrolled
    Chile: 194
    Country: Number of subjects enrolled
    Mexico: 108
    Worldwide total number of subjects
    7213
    EEA total number of subjects
    3479
    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)
    2943
    From 65 to 84 years
    4047
    85 years and over
    223

    Subject disposition

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    Recruitment
    Recruitment details
    		 Study was conducted at multiple centers in 31 countries between 23 December 2014 (first subject first visit) and 15 February 2018 (last subject last visit).

    Pre-assignment
    Screening details
    		 Overall, 7582 subjects were screened; of these 369 subjects were screen failures. A total of 7213 subjects were randomized, of which 92 never took study drug; 3562 were treated with rivaroxaban/placebo and 3559 were treated with acetylsalicylic acid/placebo.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Rivaroxaban 15 mg OD
    Arm description
    		 Subjects received rivaroxaban 15 milligram (mg) immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rivaroxaban
    Investigational medicinal product code
    BAY59-7939
    Other name
    Xarelto
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received rivaroxaban 15 mg immediate-release film-coated tablet orally OD.

    Investigational medicinal product name
    Placebo matched to acetylsalicylic acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received matching placebo of acetylsalicylic acid 100 mg enteric-coated tablet orally OD.

    Arm title
    		 Acetylsalicylic acid 100 mg OD
    Arm description
    		 Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally OD.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Acetylsalicylic acid
    Investigational medicinal product code
    BAY1019036
    Other name
    Aspirin
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received acetylsalicylic acid 100 mg enteric-coated tablet orally OD.

    Investigational medicinal product name
    Placebo matched to rivaroxaban
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received matching placebo of rivaroxaban 15 mg immediate-release film-coated tablet orally OD.

    Number of subjects in period 1
    		Rivaroxaban 15 mg OD Acetylsalicylic acid 100 mg OD
    Started
    3609
    3604
    Treated
    3562
    3559
    Completed
    3552
    3554
    Not completed
    57
    50
         Consent withdrawn by subject
    33
    33
         Lost to follow-up
    24
    17

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Rivaroxaban 15 mg OD
    Reporting group description
    		 Subjects received rivaroxaban 15 milligram (mg) immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD).

    Reporting group title
    Acetylsalicylic acid 100 mg OD
    Reporting group description
    		 Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally OD.

    Reporting group values
    		 Rivaroxaban 15 mg OD Acetylsalicylic acid 100 mg OD Total
    Number of subjects
    		 3609 3604 7213
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 66.9 ( 9.8 ) 66.9 ( 9.8 ) -
    Gender categorical
    Units: Subjects
        Female
    		 1377 1400 2777
        Male
    		 2232 2204 4436
    Race
    Units: Subjects
        White
    		 2613 2605 5218
        Black or African American
    		 51 60 111
        Asian
    		 716 698 1414
        Other
    		 229 241 470
    Stroke or TIA (prior to qualifying stroke) or Other medical history
    The other medical history refers to number of subjects with one medical history finding other than stroke or Transient ischemic attack (TIA).
    Units: Subjects
        Stroke or TIA (prior to qualifying stroke)
    		 620 643 1263
        Other medical history
    		 2989 2961 5950
    Time from qualifying stroke to randomization
    Units: days
        median (inter-quartile range (Q1-Q3))
    		 38.0 (15.0 to 89.0) 36.0 (14.0 to 86.5) -

    End points

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    End points reporting groups
    Reporting group title
    Rivaroxaban 15 mg OD
    Reporting group description
    		 Subjects received rivaroxaban 15 milligram (mg) immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally once daily (OD).

    Reporting group title
    Acetylsalicylic acid 100 mg OD
    Reporting group description
    		 Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally OD.

    Subject analysis set title
    Intention-to-treat analysis set (ITT)
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    ITT included all randomized subjects (N= 7213).

    Subject analysis set title
    Safety analysis set (SAF)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    SAF included all randomized subjects who received at least one dose of study drug (N= 7121).

    Primary: Incidence Rate of the Composite Efficacy Outcome (Adjudicated)

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    End point title
    		 Incidence Rate of the Composite Efficacy Outcome (Adjudicated)
    End point description
    Components of composite efficacy outcome (adjudicated) includes stroke (ischemic, hemorrhagic, and undefined stroke, TIA with positive neuroimaging) and systemic embolism. Incidence rate estimated as number of subjects with incident events divided by cumulative at-risk time, where subject is no longer at risk once an incident event occurred.
    End point type
    Primary
    End point timeframe
    From randomization until the efficacy cut-off date (median 326 days)
    End point values
    		 Rivaroxaban 15 mg OD Acetylsalicylic acid 100 mg OD
    Number of subjects analysed
    3609 [1]
    3604 [2]
    Units: event/100 subject-years
        number (confidence interval 95%)
    5.14 (4.40 to 5.97)
    4.78 (4.07 to 5.58)
    Notes
    [1] - ITT
    [2] - ITT
    Statistical analysis title
    		 Statistical analysis: Stroke + Systemic embolism
    Statistical analysis description
    Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
    Comparison groups
    Rivaroxaban 15 mg OD v Acetylsalicylic acid 100 mg OD
    Number of subjects included in analysis
    7213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.51884
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.33

    Primary: Incidence Rate of a Major Bleeding Event According to the International Society on Thrombosis and Haemostasis (ISTH) Criteria (Adjudicated)

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    End point title
    		 Incidence Rate of a Major Bleeding Event According to the International Society on Thrombosis and Haemostasis (ISTH) Criteria (Adjudicated)
    End point description
    Major bleeding event (as per ISTH), defined as bleeding event that met at least one of following: fatal bleeding; symptomatic bleeding in a critical area or organ (intraarticular, intramuscular with compartment syndrome, intraocular, intraspinal, pericardial, or retroperitoneal); symptomatic intracranial haemorrhage; clinically overt bleeding associated with a recent decrease in the hemoglobin level of greater than or equal to (>=) 2 grams per decilitre (g/dL) (20 grams per liter [g/L]; 1.24 millimoles per liter [mmol/L]) compared to the most recent hemoglobin value available before the event; clinically overt bleeding leading to transfusion of 2 or more units of packed red blood cells or whole blood. The results were based on classification of events that have been positively adjudicated as major bleeding events. Incidence rate estimated as number of subjects with incident events divided by cumulative at-risk time, where subject is no longer at risk once an incident event occurred.
    End point type
    Primary
    End point timeframe
    From randomization until the efficacy cut-off date (median 326 days)
    End point values
    		 Rivaroxaban 15 mg OD Acetylsalicylic acid 100 mg OD
    Number of subjects analysed
    3609 [3]
    3604 [4]
    Units: event/100 subject-years
        number (confidence interval 95%)
    1.82 (1.39 to 2.33)
    0.67 (0.42 to 1.00)
    Notes
    [3] - ITT
    [4] - ITT
    Statistical analysis title
    		 Statistical analysis: ISTH major bleeding events
    Statistical analysis description
    Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
    Comparison groups
    Rivaroxaban 15 mg OD v Acetylsalicylic acid 100 mg OD
    Number of subjects included in analysis
    7213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.00002
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    2.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.68
         upper limit
    		 4.39

    Secondary: Incidence Rate of Any of the Following: Cardiovascular Death, Recurrent Stroke, Systemic Embolism and Myocardial Infarction

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    End point title
    		 Incidence Rate of Any of the Following: Cardiovascular Death, Recurrent Stroke, Systemic Embolism and Myocardial Infarction
    End point description
    Incidence rate estimated as number of subjects with incident events divided by cumulative at-risk time, where subject is no longer at risk once an incident event occurred. Cardiovascular death includes death due to haemorrhage and death with undetermined/unknown cause. Systemic embolism is defined as abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms. The diagnosis of myocardial infarction requires the combination of: 1)evidence of myocardial necrosis (either changes in cardiac biomarkers or post-mortem pathological findings); and 2)supporting information derived from the clinical presentation, electrocardiographic changes, or the results of myocardial or coronary artery imaging.
    End point type
    Secondary
    End point timeframe
    From randomization until the efficacy cut-off date (median 326 days)
    End point values
    		 Rivaroxaban 15 mg OD Acetylsalicylic acid 100 mg OD
    Number of subjects analysed
    3609 [5]
    3604 [6]
    Units: event/100 subject-years
        number (confidence interval 95%)
    6.20 (5.38 to 7.10)
    5.85 (5.05 to 6.73)
    Notes
    [5] - ITT
    [6] - ITT
    Statistical analysis title
    		 Statistical analysis
    Statistical analysis description
    Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Confidence intervals were calculated, if at least 1 event in each treatment arm existed. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
    Comparison groups
    Acetylsalicylic acid 100 mg OD v Rivaroxaban 15 mg OD
    Number of subjects included in analysis
    7213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.56922
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.29

    Secondary: Incidence Rate of All-Cause Mortality

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    End point title
    		 Incidence Rate of All-Cause Mortality
    End point description
    All-cause mortality includes all deaths of subjects due to any cause.
    End point type
    Secondary
    End point timeframe
    From randomization until the efficacy cut-off date (median 326 days)
    End point values
    		 Rivaroxaban 15 mg OD Acetylsalicylic acid 100 mg OD
    Number of subjects analysed
    3609 [7]
    3604 [8]
    Units: event/100 subject-years
        number (confidence interval 95%)
    1.88 (1.45 to 2.40)
    1.50 (1.12 to 1.97)
    Notes
    [7] - ITT
    [8] - ITT
    Statistical analysis title
    		 Statistical analysis: All-cause mortality
    Statistical analysis description
    Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Confidence intervals were calculated, if at least 1 event in each treatment arm existed. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
    Comparison groups
    Rivaroxaban 15 mg OD v Acetylsalicylic acid 100 mg OD
    Number of subjects included in analysis
    7213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.22078
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.81

    Secondary: Incidence Rate of the Following: Stroke, Ischemic Stroke, Disabling Stroke (Modified Rankin Score >= 4), Cardiovascular Death (Including Death due to Hemorrhage and Death with Undetermined/Unknown Cause), Myocardial Infarction

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    End point title
    		 Incidence Rate of the Following: Stroke, Ischemic Stroke, Disabling Stroke (Modified Rankin Score >= 4), Cardiovascular Death (Including Death due to Hemorrhage and Death with Undetermined/Unknown Cause), Myocardial Infarction
    End point description
    Disabling stroke is defined as stroke with modified Rankin score (mRS) greater than or equal to (>=) 4 as assessed by investigator. mRS spans 0-6, running from perfect health to death. A score of 0-3 indicates functional status ranging from no symptoms to "moderate disability" (defined in the mRS as requiring some help, but able to walk without assistance); mRS 4-6 indicates functional status ranging from "moderately severe disability" (unable to walk or to attend to own bodily needs without assistance) through to death. CV death includes death due to haemorrhage and death with undetermined/unknown cause. Diagnosis of myocardial infarction requires combination of: 1) evidence of myocardial necrosis (either changes in cardiac biomarkers or post-mortem pathological findings); 2) supporting information derived from clinical presentation, electrocardiographic changes, or results of myocardial or coronary artery imaging.
    End point type
    Secondary
    End point timeframe
    From randomization until the efficacy cut-off date (median 326 days)
    End point values
    		 Rivaroxaban 15 mg OD Acetylsalicylic acid 100 mg OD
    Number of subjects analysed
    3609 [9]
    3604 [10]
    Units: event/100 subject-years
    number (confidence interval 95%)
        Stroke
    5.11 (4.37 to 5.93)
    4.71 (4.01 to 5.51)
        Ischemic stroke
    4.71 (4.01 to 5.51)
    4.56 (3.87 to 5.34)
        Disabling stroke
    1.20 (0.86 to 1.62)
    0.84 (0.56 to 1.21)
        CVdeath (includes death due to hemorrhage)
    0.99 (0.68 to 1.38)
    0.66 (0.42 to 1.00)
        Myocardial infarction
    0.49 (0.29 to 0.79)
    0.67 (0.42 to 1.00)
    Notes
    [9] - ITT
    [10] - ITT
    Statistical analysis title
    		 Statistical analysis 1: Stroke
    Statistical analysis description
    Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
    Comparison groups
    Rivaroxaban 15 mg OD v Acetylsalicylic acid 100 mg OD
    Number of subjects included in analysis
    7213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4797
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.34
    Statistical analysis title
    		 Statistical analysis 2: Ischemic stroke
    Statistical analysis description
    Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
    Comparison groups
    Rivaroxaban 15 mg OD v Acetylsalicylic acid 100 mg OD
    Number of subjects included in analysis
    7213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.78738
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.29
    Statistical analysis title
    		 Statistical analysis 3: Disabling stroke
    Statistical analysis description
    Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
    Comparison groups
    Rivaroxaban 15 mg OD v Acetylsalicylic acid 100 mg OD
    Number of subjects included in analysis
    7213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.14822
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 2.28
    Statistical analysis title
    		 Statistical analysis 4: CV death
    Statistical analysis description
    Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
    Comparison groups
    Rivaroxaban 15 mg OD v Acetylsalicylic acid 100 mg OD
    Number of subjects included in analysis
    7213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.14051
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 2.52
    Statistical analysis title
    		 Statistical analysis 5: Myocardial infarction
    Statistical analysis description
    Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
    Comparison groups
    Rivaroxaban 15 mg OD v Acetylsalicylic acid 100 mg OD
    Number of subjects included in analysis
    7213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.34284
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.39
         upper limit
    		 1.38

    Secondary: Incidence Rate of Life-Threatening Bleeding Events

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    End point title
    		 Incidence Rate of Life-Threatening Bleeding Events
    End point description
    Life-threatening bleeding was defined as a subset of major bleeding that met at least one of the following criteria: 1) fatal bleeding; 2) symptomatic intracranial haemorrhage; 3) reduction in hemoglobin of at least 5 g/dl (50 g/l; 3.10 mmol/L); 4) transfusion of at least 4 units of packed red cells or whole blood; 5) associated with hypotension requiring the use of intravenous inotropic agents; 6) necessitated surgical intervention. Incidence rate estimated as number of subjects with incident events divided by cumulative at-risk time, where subject is no longer at risk once an incident event occurred.
    End point type
    Secondary
    End point timeframe
    From randomization until the efficacy cut-off date (median 326 days)
    End point values
    		 Rivaroxaban 15 mg OD Acetylsalicylic acid 100 mg OD
    Number of subjects analysed
    3609 [11]
    3604 [12]
    Units: event/100 subject-years
        number (confidence interval 95%)
    1.02 (0.71 to 1.42)
    0.43 (0.24 to 0.72)
    Notes
    [11] - ITT
    [12] - ITT
    Statistical analysis title
    		 Statistical analysis
    Statistical analysis description
    Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
    Comparison groups
    Rivaroxaban 15 mg OD v Acetylsalicylic acid 100 mg OD
    Number of subjects included in analysis
    7213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.00443
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    2.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.28
         upper limit
    		 4.29

    Secondary: Incidence Rate of Clinically Relevant Non-Major Bleeding Events

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    End point title
    		 Incidence Rate of Clinically Relevant Non-Major Bleeding Events
    End point description
    Non-major clinically relevant bleeding was defined as non-major overt bleeding but required medical attention (example: hospitalization, medical treatment for bleeding), and/or was associated with the study drug interruption of more than 14 days. The results were based on the outcome events at or after randomization until the efficacy cut-off date. Incidence rate estimated as number of subjects with incident events divided by cumulative at-risk time, where subject is no longer at risk once an incident event occurred.
    End point type
    Secondary
    End point timeframe
    From randomization until the efficacy cut-off date (median 326 days)
    End point values
    		 Rivaroxaban 15 mg OD Acetylsalicylic acid 100 mg OD
    Number of subjects analysed
    3609 [13]
    3604 [14]
    Units: event/100 subject-years
        number (confidence interval 95%)
    3.52 (2.91 to 4.21)
    2.32 (1.84 to 2.90)
    Notes
    [13] - ITT
    [14] - ITT
    Statistical analysis title
    		 Statistical analysis
    Statistical analysis description
    Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
    Comparison groups
    Rivaroxaban 15 mg OD v Acetylsalicylic acid 100 mg OD
    Number of subjects included in analysis
    7213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.00451
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.13
         upper limit
    		 2

    Secondary: Incidence Rate of Intracranial Hemorrhage

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    End point title
    		 Incidence Rate of Intracranial Hemorrhage
    End point description
    Intracranial hemorrhage included all bleeding events that occurred in intracerebral, subarachnoidal as well as subdural or epidural sites. The below table displays results for all randomized subjects and the outcomes at or after randomization until the efficacy cut-off date. Incidence rate estimated as number of subjects with incident events divided by cumulative at-risk time, where subject is no longer at risk once an incident event occurred.
    End point type
    Secondary
    End point timeframe
    From randomization until the efficacy cut-off date (median 326 days)
    End point values
    		 Rivaroxaban 15 mg OD Acetylsalicylic acid 100 mg OD
    Number of subjects analysed
    3609 [15]
    3604 [16]
    Units: event/100 subject-years
        number (confidence interval 95%)
    0.70 (0.45 to 1.04)
    0.35 (0.18 to 0.61)
    Notes
    [15] - ITT
    [16] - ITT
    Statistical analysis title
    		 Statistical analysis
    Statistical analysis description
    Risk reduction was estimated with the stratified Cox proportional hazards model. Hazard ratios (95% confidence interval) as compared to acetylsalicylic acid arm were reported. Rivaroxaban treatment was compared with the Acetylsalicylic acid control group using a stratified log-rank test. P-values (two-sided) as compared to acetylsalicylic acid arm were based on the log-rank test.
    Comparison groups
    Rivaroxaban 15 mg OD v Acetylsalicylic acid 100 mg OD
    Number of subjects included in analysis
    7213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.04409
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    2.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1
         upper limit
    		 4.02

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From start of study drug administration until 2 days after the last dose of study drug
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Rivaroxaban 15 mg OD
    Reporting group description
    		 Subjects received rivaroxaban 15 mg immediate-release film-coated tablet and matching placebo of acetylsalicylic acid orally OD up to end of treatment.

    Reporting group title
    Acetylsalicylic acid 100 mg OD
    Reporting group description
    		 Subjects received acetylsalicylic acid 100 mg enteric-coated tablet and matching placebo of rivaroxaban orally OD up to end of treatment.

    Serious adverse events
    		 Rivaroxaban 15 mg OD Acetylsalicylic acid 100 mg OD
    Total subjects affected by serious adverse events
         subjects affected / exposed
    466 / 3562 (13.08%)
    434 / 3559 (12.19%)
         number of deaths (all causes)
    73
    58
         number of deaths resulting from adverse events
    15
    20
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute lymphocytic leukaemia
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenocarcinoma
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenocarcinoma gastric
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    B-cell lymphoma
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    3 / 3562 (0.08%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bile duct adenocarcinoma
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Bladder cancer
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Bladder neoplasm
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain neoplasm malignant
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cervix carcinoma
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    3 / 3562 (0.08%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Colorectal cancer stage IV
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Essential thrombocythaemia
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fallopian tube cancer
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gallbladder cancer
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal carcinoma
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Kaposi's sarcoma
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hodgkin's disease
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    1 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lung adenocarcinoma stage IV
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung carcinoma cell type unspecified stage IV
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lymphoma
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to bone
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal adenocarcinoma
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-Hodgkin's lymphoma
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal carcinoma
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Oropharyngeal cancer
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         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
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parathyroid tumour
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal adenocarcinoma
         subjects affected / exposed
    1 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal cancer
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal cancer stage III
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal meningioma benign
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (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 of lung
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    3 / 3562 (0.08%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of the tongue
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal adenoma
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (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 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal adenocarcinoma
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 3562 (0.03%)
    5 / 3559 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Neuroendocrine tumour
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma stage IV
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    1 / 3562 (0.03%)
    8 / 3559 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign bone neoplasm
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain neoplasm
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal neoplasm
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal squamous cell carcinoma
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pituitary tumour benign
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic neoplasm
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Thyroid cancer
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastatic uterine cancer
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Inflammatory pseudotumour
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant neoplasm of unknown primary site
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hepatic cancer
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive breast carcinoma
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    3 / 3562 (0.08%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic aneurysm rupture
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolism venous
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    4 / 3562 (0.11%)
    6 / 3559 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphoedema
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral vascular disorder
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Temporal arteritis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombophlebitis superficial
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Varicose vein
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post thrombotic syndrome
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    May-Thurner syndrome
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    5 / 3562 (0.14%)
    5 / 3559 (0.14%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Finger amputation
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial septal defect repair
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 3562 (0.00%)
    3 / 3559 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hernia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         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 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral swelling
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    3 / 3562 (0.08%)
    4 / 3559 (0.11%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaphylactic shock
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Corneal graft rejection
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    4 / 3562 (0.11%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Menorrhagia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peyronie's disease
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine prolapse
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometrial dysplasia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Genital haemorrhage
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    3 / 3562 (0.08%)
    3 / 3559 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hiccups
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Idiopathic pulmonary fibrosis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    3 / 3562 (0.08%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 3562 (0.03%)
    8 / 3559 (0.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pulmonary oedema
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         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
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial disorder
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Alcohol abuse
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adjustment disorder with mixed anxiety and depressed mood
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcoholism
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Conversion disorder
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    2 / 3562 (0.06%)
    3 / 3559 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    3 / 3562 (0.08%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression suicidal
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disorientation
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (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 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intentional self-injury
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mania
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obsessive-compulsive personality disorder
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Panic disorder
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Panic reaction
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Schizophrenia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Somnambulism
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcohol withdrawal syndrome
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcohol use disorder
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neurologic somatic symptom disorder
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device malfunction
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    4 / 3562 (0.11%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary colic
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis acute
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    3 / 3562 (0.08%)
    4 / 3559 (0.11%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    6 / 3562 (0.17%)
    3 / 3559 (0.08%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cirrhosis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis acute
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    C-reactive protein increased
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eosinophil count increased
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         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
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatic specific antigen increased
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza A virus test positive
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test increased
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anastomotic ulcer haemorrhage
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    3 / 3562 (0.08%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carbon monoxide poisoning
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Compression fracture
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    3 / 3562 (0.08%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    6 / 3562 (0.17%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    5 / 3562 (0.14%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         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
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 3562 (0.03%)
    5 / 3559 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    2 / 3562 (0.06%)
    3 / 3559 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intentional overdose
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament sprain
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Medication error
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 3562 (0.00%)
    4 / 3559 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Spinal compression fracture
         subjects affected / exposed
    3 / 3562 (0.08%)
    3 / 3559 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic fracture
         subjects affected / exposed
    0 / 3562 (0.00%)
    3 / 3559 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle strain
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Face injury
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial restenosis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain contusion
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transplant failure
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         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 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic intracranial haemorrhage
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament rupture
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone contusion
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal column injury
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pubis fracture
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    0 / 3562 (0.00%)
    3 / 3559 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incorrect dosage administered
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic haemothorax
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb fracture
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Atrial septal defect
         subjects affected / exposed
    1 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bicuspid aortic valve
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydrocele
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary arteriovenous fistula
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia supraventricular
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    36 / 3562 (1.01%)
    37 / 3559 (1.04%)
         occurrences causally related to treatment / all
    0 / 36
    0 / 37
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    5 / 3562 (0.14%)
    3 / 3559 (0.08%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    1 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac amyloidosis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac failure
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    3 / 3562 (0.08%)
    3 / 3559 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Conduction disorder
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    3 / 3562 (0.08%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive heart disease
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    1 / 3562 (0.03%)
    3 / 3559 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    3 / 3562 (0.08%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial thrombosis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular hypokinesia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery insufficiency
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocarditis noninfective
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Amyotrophic lateral sclerosis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Autonomic nervous system imbalance
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         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
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain stem haemorrhage
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Cerebellar haemorrhage
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral venous thrombosis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         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
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chorea
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Demyelination
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic neuropathy
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    2 / 3562 (0.06%)
    4 / 3559 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    7 / 3562 (0.20%)
    8 / 3559 (0.22%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial paralysis
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    2 / 3562 (0.06%)
    3 / 3559 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    1 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Migraine with aura
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple sclerosis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorder
         subjects affected / exposed
    1 / 3562 (0.03%)
    4 / 3559 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelopathy
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyneuropathy
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post herpetic neuralgia
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    9 / 3562 (0.25%)
    9 / 3559 (0.25%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Syncope
         subjects affected / exposed
    10 / 3562 (0.28%)
    8 / 3559 (0.22%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient global amnesia
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tension headache
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical radiculopathy
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebrobasilar insufficiency
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thalamus haemorrhage
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Putamen haemorrhage
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stroke in evolution
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Partial seizures
         subjects affected / exposed
    5 / 3562 (0.14%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parkinson's disease
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral artery stenosis
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral arteriosclerosis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Central pain syndrome
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post stroke seizure
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemianaesthesia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudostroke
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Focal dyscognitive seizures
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparaesthesia
         subjects affected / exposed
    1 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    8 / 3562 (0.22%)
    3 / 3559 (0.08%)
         occurrences causally related to treatment / all
    3 / 8
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Anaemia macrocytic
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Antiphospholipid syndrome
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    4 / 3562 (0.11%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Microcytic anaemia
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         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 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombotic thrombocytopenic purpura
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Meniere's disease
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo positional
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Blindness
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (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
    4 / 3562 (0.11%)
    8 / 3559 (0.22%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diplopia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eyelid ptosis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glaucoma
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Macular oedema
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Visual impairment
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Macular fibrosis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ophthalmic vein thrombosis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dental caries
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    1 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal fistula
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (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 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    7 / 3562 (0.20%)
    5 / 3559 (0.14%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         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
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Large intestinal ulcer
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 3562 (0.00%)
    3 / 3559 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatolithiasis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (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
    4 / 3562 (0.11%)
    3 / 3559 (0.08%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric volvulus
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric mucosal lesion
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erosive duodenitis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal fissure
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         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
    Dermatomyositis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erythema multiforme
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psoriasis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin reaction
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic foot
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute prerenal failure
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cyst
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    2 / 3562 (0.06%)
    3 / 3559 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal haematoma
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal hypertension
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Costovertebral angle tenderness
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Urethral stenosis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    4 / 3562 (0.11%)
    6 / 3559 (0.17%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Ureterolithiasis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Basedow's disease
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Goitre
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperparathyroidism
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperthyroidism
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thyroiditis subacute
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    1 / 3562 (0.03%)
    3 / 3559 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fasciitis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gouty arthritis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Groin pain
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle spasms
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    11 / 3562 (0.31%)
    3 / 3559 (0.08%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (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 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periarthritis
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Synovial cyst
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myofascial pain syndrome
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle tightness
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    3 / 3562 (0.08%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb discomfort
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Plica syndrome
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebral foraminal stenosis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis perforated
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (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
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Atypical pneumonia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain abscess
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cellulitis
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Corneal abscess
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic gangrene
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalitis viral
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endophthalmitis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    6 / 3562 (0.17%)
    3 / 3559 (0.08%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis A
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (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 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kidney infection
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         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
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis externa
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paronychia
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritoneal abscess
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (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
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    14 / 3562 (0.39%)
    14 / 3559 (0.39%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 14
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Postoperative wound infection
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis chronic
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (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 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    3 / 3562 (0.08%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tooth abscess
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    6 / 3562 (0.17%)
    6 / 3559 (0.17%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vestibular neuronitis
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    3 / 3562 (0.08%)
    4 / 3559 (0.11%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia necrotising
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal infection
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    3 / 3562 (0.08%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neurocysticercosis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis infectious
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal abscess
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bursitis infective
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         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
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perichondritis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    3 / 3562 (0.08%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acarodermatitis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster oticus
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection viral
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary tract infection bacterial
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    4 / 3562 (0.11%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    1 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 3562 (0.03%)
    6 / 3559 (0.17%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obesity
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock hypoglycaemic
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic complication
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic metabolic decompensation
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adult failure to thrive
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Rivaroxaban 15 mg OD Acetylsalicylic acid 100 mg OD
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    308 / 3562 (8.65%)
    294 / 3559 (8.26%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basosquamous carcinoma
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Breast cancer
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Breast neoplasm
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Essential thrombocythaemia
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Superficial spreading melanoma stage unspecified
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Metastases to bone
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Vascular disorders
    Flushing
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Hypertension
         subjects affected / exposed
    11 / 3562 (0.31%)
    7 / 3559 (0.20%)
         occurrences all number
    11
    8
    Aortic aneurysm
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences all number
    2
    1
    Hypertensive crisis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Hypotension
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences all number
    2
    1
    Intermittent claudication
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Varicose vein
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Phlebitis superficial
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Thrombophlebitis superficial
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences all number
    0
    2
    Peripheral arterial occlusive disease
         subjects affected / exposed
    3 / 3562 (0.08%)
    0 / 3559 (0.00%)
         occurrences all number
    3
    0
    Deep vein thrombosis
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences all number
    2
    1
    Vascular pain
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Surgical and medical procedures
    Tooth extraction
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences all number
    3
    2
    Implantable cardiac monitor insertion
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Cataract operation
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences all number
    2
    0
    Chest discomfort
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Chest pain
         subjects affected / exposed
    3 / 3562 (0.08%)
    4 / 3559 (0.11%)
         occurrences all number
    3
    4
    Discomfort
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences all number
    2
    0
    Fatigue
         subjects affected / exposed
    2 / 3562 (0.06%)
    3 / 3559 (0.08%)
         occurrences all number
    2
    3
    Chills
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Malaise
         subjects affected / exposed
    1 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences all number
    1
    2
    Gait disturbance
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Oedema peripheral
         subjects affected / exposed
    1 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences all number
    1
    2
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences all number
    2
    0
    Peripheral swelling
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences all number
    2
    2
    Immune system disorders
    Allergy to arthropod sting
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Hypersensitivity
         subjects affected / exposed
    3 / 3562 (0.08%)
    1 / 3559 (0.03%)
         occurrences all number
    3
    3
    Social circumstances
    Treatment noncompliance
         subjects affected / exposed
    2 / 3562 (0.06%)
    5 / 3559 (0.14%)
         occurrences all number
    2
    5
    Reproductive system and breast disorders
    Breast mass
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Prostatomegaly
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Prostatitis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Dyspnoea
         subjects affected / exposed
    4 / 3562 (0.11%)
    1 / 3559 (0.03%)
         occurrences all number
    4
    1
    Dry throat
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Epistaxis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Cough
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Hiccups
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Pharyngeal ulceration
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Pulmonary embolism
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Pulmonary microemboli
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Depression
         subjects affected / exposed
    3 / 3562 (0.08%)
    2 / 3559 (0.06%)
         occurrences all number
    3
    2
    Anxiety
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Impatience
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Abulia
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Anxiety disorder
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Panic attack
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Mental disorder due to a general medical condition
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Adjustment disorder
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Post stroke depression
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences all number
    2
    0
    Hepatobiliary disorders
    Biliary colic
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Hepatic function abnormal
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences all number
    2
    2
    Hypertransaminasaemia
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Hepatitis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Coagulation factor VIII level increased
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Glomerular filtration rate decreased
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Visual acuity tests abnormal
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Heart rate increased
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Haemoglobin decreased
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Transaminases increased
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Weight decreased
         subjects affected / exposed
    1 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences all number
    1
    2
    Liver function test increased
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Injury, poisoning and procedural complications
    Accident
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences all number
    0
    2
    Alcohol poisoning
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Concussion
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Fall
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Foot fracture
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Head injury
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Humerus fracture
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Inappropriate schedule of drug administration
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    2
    0
    Medication error
         subjects affected / exposed
    10 / 3562 (0.28%)
    9 / 3559 (0.25%)
         occurrences all number
    10
    9
    Overdose
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences all number
    2
    0
    Radius fracture
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Rib fracture
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences all number
    2
    0
    Face injury
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Tendon rupture
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Contusion
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Limb injury
         subjects affected / exposed
    3 / 3562 (0.08%)
    1 / 3559 (0.03%)
         occurrences all number
    3
    1
    Drug administration error
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Incorrect dose administered
         subjects affected / exposed
    6 / 3562 (0.17%)
    4 / 3559 (0.11%)
         occurrences all number
    6
    4
    Upper limb fracture
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Incorrect dosage administered
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences all number
    2
    1
    Skin wound
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Labelled drug-drug interaction medication error
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Intentional product misuse
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences all number
    2
    1
    Medication monitoring error
         subjects affected / exposed
    1 / 3562 (0.03%)
    3 / 3559 (0.08%)
         occurrences all number
    1
    3
    Congenital, familial and genetic disorders
    Atrial septal defect
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Factor V Leiden mutation
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Fabry's disease
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Atrial fibrillation
         subjects affected / exposed
    60 / 3562 (1.68%)
    60 / 3559 (1.69%)
         occurrences all number
    60
    60
    Atrial flutter
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences all number
    2
    0
    Atrial tachycardia
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Cardiac failure
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Coronary artery disease
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Cardiac failure congestive
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Myocardial ischaemia
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences all number
    2
    0
    Palpitations
         subjects affected / exposed
    3 / 3562 (0.08%)
    1 / 3559 (0.03%)
         occurrences all number
    3
    1
    Sinus arrhythmia
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Sinus tachycardia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Supraventricular extrasystoles
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Intracardiac thrombus
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Ventricular fibrillation
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Tachycardia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Cardiac flutter
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Amnesia
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Aphasia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Cerebrovascular accident
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Dizziness postural
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Dementia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Dizziness
         subjects affected / exposed
    5 / 3562 (0.14%)
    7 / 3559 (0.20%)
         occurrences all number
    6
    7
    Dysarthria
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Facial paralysis
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Epilepsy
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Dysgeusia
         subjects affected / exposed
    1 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences all number
    1
    2
    Migraine
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Lethargy
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Hypoaesthesia
         subjects affected / exposed
    1 / 3562 (0.03%)
    3 / 3559 (0.08%)
         occurrences all number
    1
    3
    Headache
         subjects affected / exposed
    10 / 3562 (0.28%)
    8 / 3559 (0.22%)
         occurrences all number
    10
    9
    Parkinsonism
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Presyncope
         subjects affected / exposed
    1 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences all number
    1
    2
    Paraesthesia
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Sensory disturbance
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Seizure
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Somnolence
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Sciatica
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences all number
    2
    0
    Syncope
         subjects affected / exposed
    2 / 3562 (0.06%)
    3 / 3559 (0.08%)
         occurrences all number
    2
    4
    Speech disorder
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Vertebral artery occlusion
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Cervical radiculopathy
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Facial paresis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    IIIrd nerve paresis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Cognitive disorder
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Hyposmia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Stroke in evolution
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Partial seizures
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Parkinson's disease
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Vascular dementia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Autonomic neuropathy
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Cerebral artery stenosis
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Occipital neuralgia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences all number
    2
    2
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Antiphospholipid syndrome
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences all number
    2
    0
    Thrombocytosis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Thrombocytopenia
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences all number
    2
    1
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Vertigo positional
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences all number
    2
    2
    Vertigo
         subjects affected / exposed
    2 / 3562 (0.06%)
    4 / 3559 (0.11%)
         occurrences all number
    2
    4
    Eye disorders
    Diabetic retinopathy
         subjects affected / exposed
    1 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences all number
    1
    2
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Cataract
         subjects affected / exposed
    1 / 3562 (0.03%)
    2 / 3559 (0.06%)
         occurrences all number
    2
    2
    Episcleritis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Dry eye
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Eyelid ptosis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Keratitis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Pterygium
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Retinal vein occlusion
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Vision blurred
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Conjunctival hyperaemia
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    2
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Abdominal pain lower
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Abdominal pain
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    5 / 3562 (0.14%)
    7 / 3559 (0.20%)
         occurrences all number
    5
    7
    Cheilitis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Chronic gastritis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Constipation
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences all number
    2
    1
    Diarrhoea
         subjects affected / exposed
    8 / 3562 (0.22%)
    3 / 3559 (0.08%)
         occurrences all number
    8
    3
    Defaecation urgency
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Dyspepsia
         subjects affected / exposed
    2 / 3562 (0.06%)
    3 / 3559 (0.08%)
         occurrences all number
    2
    4
    Eructation
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Gastritis erosive
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences all number
    0
    2
    Gastritis
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences all number
    2
    2
    Gastric ulcer
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences all number
    0
    2
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Gastrointestinal disorder
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Gingival swelling
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    2
    Gingival bleeding
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Hyperchlorhydria
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Haemorrhoids
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Inguinal hernia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Lip swelling
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Inflammatory bowel disease
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Nausea
         subjects affected / exposed
    5 / 3562 (0.14%)
    1 / 3559 (0.03%)
         occurrences all number
    5
    1
    Oesophagitis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Toothache
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Vomiting
         subjects affected / exposed
    2 / 3562 (0.06%)
    4 / 3559 (0.11%)
         occurrences all number
    2
    4
    Retching
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Palatal disorder
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Colitis microscopic
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Dermatitis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Angioedema
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    2
    Alopecia
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Dermatitis allergic
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Drug eruption
         subjects affected / exposed
    0 / 3562 (0.00%)
    3 / 3559 (0.08%)
         occurrences all number
    0
    3
    Eczema
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Erythema
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Rash erythematous
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Rash
         subjects affected / exposed
    4 / 3562 (0.11%)
    4 / 3559 (0.11%)
         occurrences all number
    4
    4
    Pruritus
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Rash pruritic
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Skin lesion
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Urticaria
         subjects affected / exposed
    2 / 3562 (0.06%)
    3 / 3559 (0.08%)
         occurrences all number
    2
    3
    Rash papular
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Solar lentigo
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Precancerous skin lesion
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Skin swelling
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Nephrolithiasis
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences all number
    2
    0
    Renal colic
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Renal failure
         subjects affected / exposed
    3 / 3562 (0.08%)
    0 / 3559 (0.00%)
         occurrences all number
    3
    0
    Renal impairment
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences all number
    2
    2
    Chronic kidney disease
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Ureterolithiasis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Urinary incontinence
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Thyroiditis subacute
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Thyroid mass
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    4 / 3562 (0.11%)
    3 / 3559 (0.08%)
         occurrences all number
    4
    3
    Arthralgia
         subjects affected / exposed
    1 / 3562 (0.03%)
    4 / 3559 (0.11%)
         occurrences all number
    1
    4
    Arthritis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Bursitis
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Gouty arthritis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Chondrocalcinosis pyrophosphate
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Joint swelling
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Metatarsalgia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Haemarthrosis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Myalgia
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences all number
    2
    2
    Musculoskeletal pain
         subjects affected / exposed
    1 / 3562 (0.03%)
    4 / 3559 (0.11%)
         occurrences all number
    1
    4
    Muscular weakness
         subjects affected / exposed
    2 / 3562 (0.06%)
    2 / 3559 (0.06%)
         occurrences all number
    2
    2
    Muscle spasms
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences all number
    2
    0
    Myopathy
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Osteoarthritis
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences all number
    2
    1
    Osteochondrosis
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Pain in extremity
         subjects affected / exposed
    3 / 3562 (0.08%)
    1 / 3559 (0.03%)
         occurrences all number
    3
    1
    Periostitis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Plantar fasciitis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Tenosynovitis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 3562 (0.00%)
    2 / 3559 (0.06%)
         occurrences all number
    0
    2
    Synovial cyst
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Tendonitis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Limb mass
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Diarrhoea infectious
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Cystitis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Gastroenteritis
         subjects affected / exposed
    3 / 3562 (0.08%)
    1 / 3559 (0.03%)
         occurrences all number
    3
    1
    Influenza
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    2
    Herpes zoster
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    2
    0
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Pneumonia
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Pneumonia viral
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences all number
    2
    2
    Urinary tract infection
         subjects affected / exposed
    3 / 3562 (0.08%)
    4 / 3559 (0.11%)
         occurrences all number
    3
    4
    Vaginal infection
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Vulvovaginitis trichomonal
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Helicobacter infection
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Alveolar osteitis
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Lung infection
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    2 / 3562 (0.06%)
    0 / 3559 (0.00%)
         occurrences all number
    2
    0
    Haemochromatosis
         subjects affected / exposed
    1 / 3562 (0.03%)
    0 / 3559 (0.00%)
         occurrences all number
    1
    0
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Electrolyte imbalance
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Gout
         subjects affected / exposed
    1 / 3562 (0.03%)
    1 / 3559 (0.03%)
         occurrences all number
    1
    1
    Hyperglycaemia
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1
    Type 2 diabetes mellitus
         subjects affected / exposed
    2 / 3562 (0.06%)
    1 / 3559 (0.03%)
         occurrences all number
    2
    1
    Decreased appetite
         subjects affected / exposed
    0 / 3562 (0.00%)
    1 / 3559 (0.03%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Nov 2015
    The following eligibility criteria were revised: •More details were provided in definition of a lacunar stroke. •Subjects were to be included if there was no stenosis greater than (>) 50% rather than greater than or equal to (>=) 50%. •They were to be excluded if there was an intracranial stenosis > 50%. •For subjects with intracranial arterial occlusions in territory of qualifying stroke, it was clarified that a subject was eligible if investigator believed the occlusion was due to embolism, and not atherosclerotic based on absence of intracranial atherosclerosis elsewhere. •For 24-hour cardiac rhythm monitoring assessment to exclude the presence of Atrial fibrillation (AF), an allowance was added to accept a 20-hour recording to reflect routine practice. •For determination of intra-cardiac thrombus, allowance of transesophageal echocardiography was added as well as transthoracic echocardiography. •Recruitment of subjects was changed from 18 years or older to 50 years of age or older. •Additional clarifications were made to the inclusion criteria regarding subjects enrolled with certain risk factors: •Clarification that covert/silent strokes on neuroimaging and current tobacco smoker counted as risk factors. •Clarification that each risk factor counted separately (for example, “stroke or Transient ischemic attack (TIA) prior to index stroke, diabetes, hypertension, and heart failure” changed to “stroke or TIA prior to index stroke [includes covert/silent strokes on neuroimaging], diabetes, hypertension, current tobacco smoker, or heart failure”). •Age restriction changed from less than (<) 60 years of age with a cap at 10% of the total study population to ≥ 50 years and requirement for an additional risk factor for subjects between 50-59 years. •A statement was added that enrollment in the age group 50-59 years might have been stopped based on a blinded review of the observed overall event rate of confirmed primary efficacy outcomes during the study.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    05 Oct 2017
    The study was terminated early on recommendation of the IDMC and concurrence of the co-principal investigators and the sponsor due to no efficacy improvement over aspirin at an interim analysis and very little chance of showing overall benefit if study were completed.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Decimal places were automatically truncated if last decimals is equals to zero.

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/29525076
    http://www.ncbi.nlm.nih.gov/pubmed/29766772
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