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    Clinical Trial Results:
    Multicenter, Randomized, Active-Controlled Efficacy And Safety Study Comparing Extended Duration Betrixaban With Standard Of Care Enoxaparin For The Prevention Of Venous Thromboembolism In Acute Medically Ill Patients

    Summary
    EudraCT number
    		 2012-000255-13
    Trial protocol
    		 BE   LV   DE   ES   GB   PL   LT   AT   DK   CZ   BG   IT   FI   SK  
    Global end of trial date
    31 Jan 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    02 Dec 2017
    First version publication date
    02 Dec 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    11-019
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01583218
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Portola Pharmaceuticals, Inc.
    Sponsor organisation address
    270 East Grand Avenue, South San Francisco, United States,
    Public contact
    Janice Castillo (VP Reg Affairs), Portola Pharmaceuticals, Inc., 001 650-246-7360, jcastillo@portola.com
    Scientific contact
    Janice Castillo (VP Reg Affairs), Portola Pharmaceuticals, Inc., 001 650-246-7360, jcastillo@portola.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    26 Apr 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 Dec 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Jan 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Demonstrate the superiority of extended duration (35 days + 7 day window, i.e. 35-42 days allowed) anticoagulation with betrixaban as compared to the standard of care (10 ± 4 days) with enoxaparin for prevention of VTE in patients who are at risk due to acute medical illness
    Protection of trial subjects
    The conduct of this clinical study met 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 Conference on Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent explained to all subjects and/or their legally authorized representative. Participating subjects and/or their legally authorized representative signed informed consent form and could withdraw from the study at any time. 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
    30 Mar 2012
    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: 369
    Country: Number of subjects enrolled
    Slovakia: 105
    Country: Number of subjects enrolled
    Spain: 412
    Country: Number of subjects enrolled
    United Kingdom: 22
    Country: Number of subjects enrolled
    Austria: 15
    Country: Number of subjects enrolled
    Belgium: 15
    Country: Number of subjects enrolled
    Bulgaria: 431
    Country: Number of subjects enrolled
    Czech Republic: 237
    Country: Number of subjects enrolled
    Denmark: 12
    Country: Number of subjects enrolled
    Estonia: 205
    Country: Number of subjects enrolled
    Finland: 26
    Country: Number of subjects enrolled
    France: 292
    Country: Number of subjects enrolled
    Germany: 196
    Country: Number of subjects enrolled
    Hungary: 252
    Country: Number of subjects enrolled
    Italy: 261
    Country: Number of subjects enrolled
    Latvia: 319
    Country: Number of subjects enrolled
    Lithuania: 470
    Country: Number of subjects enrolled
    Singapore: 1
    Country: Number of subjects enrolled
    Belarus: 69
    Country: Number of subjects enrolled
    Croatia: 92
    Country: Number of subjects enrolled
    Georgia: 260
    Country: Number of subjects enrolled
    Romania: 170
    Country: Number of subjects enrolled
    Russian Federation: 971
    Country: Number of subjects enrolled
    Serbia: 115
    Country: Number of subjects enrolled
    Turkey: 54
    Country: Number of subjects enrolled
    Ukraine: 886
    Country: Number of subjects enrolled
    Australia: 20
    Country: Number of subjects enrolled
    Israel: 99
    Country: Number of subjects enrolled
    South Africa: 91
    Country: Number of subjects enrolled
    Argentina: 215
    Country: Number of subjects enrolled
    Brazil: 57
    Country: Number of subjects enrolled
    Chile: 44
    Country: Number of subjects enrolled
    Peru: 152
    Country: Number of subjects enrolled
    Canada: 51
    Country: Number of subjects enrolled
    United States: 527
    Worldwide total number of subjects
    7513
    EEA total number of subjects
    3901
    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)
    782
    From 65 to 84 years
    5569
    85 years and over
    1162

    Subject disposition

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    Recruitment
    Recruitment details
    		 Patients enrolled with one of the diagnoses: acutely decompensated heart failure, acute respiratory failure, acute infection, rheumatic disease, and ischemic stroke. They also were required to meet additional criteria that placed them at high prolonged risk of VTE. Patients were randomized 1:1 to either betrixaban or enoxaparin treatment group.

    Pre-assignment
    Screening details
    		 To maintain the blind, patients assigned to the betrixaban group received betrixaban capsules for 35 to 42 days and daily subcutaneous (SQ) injections of enoxaparin placebo for 10 ± 4 days, and patients assigned to the enoxaparin group received daily SQ injections of enoxaparin for 10 ± 4 days and betrixaban placebo capsules for 35 to 42 days.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Betrixaban
    Arm description
    		 Daily oral (PO) betrixaban capsules for 35 to 42 days and subcutaneous (SQ) injections of enoxaparin placebo for 10 ± 4 days
    Arm type
    		 Experimental

    Investigational medicinal product name
    Betrixaban
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Daily oral (PO) betrixaban capsules for 35 to 42 days

    Arm title
    		 Enoxaparin
    Arm description
    		 Daily subcutaneous (SQ) injections of enoxaparin for 10 ± 4 days and oral (PO) betrixaban placebo capsules for 35 to 42 days
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Enoxaparin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Daily subcutaneous (SQ) injections of enoxaparin for 10 ± 4 days

    Number of subjects in period 1
    		Betrixaban Enoxaparin
    Started
    3759
    3754
    Completed
    3470
    3471
    Not completed
    289
    283
         Adverse event, serious fatal
    206
    211
         Patient was randomized due to mistake
    1
    -
         Patient deemed ineligible after randomization
    2
    -
         Subject moved to another province
    -
    1
         Cannot Contact Patient Directly
    1
    2
         WOC on day of randomization, no IP administered
    1
    -
         Patient was early terminated from the study
    -
    1
         Patient randomized but not dosed
    17
    16
         Consent withdrawn by subject
    43
    29
         Adverse event, non-fatal
    3
    3
         Patient did not wish to attend visit at the clinic
    -
    1
         Patient/Family Decision
    3
    -
         Source document/coordinator missing
    -
    2
         Lost to follow-up
    11
    17
         Patient was assessed via phone in person
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Betrixaban
    Reporting group description
    		 Daily oral (PO) betrixaban capsules for 35 to 42 days and subcutaneous (SQ) injections of enoxaparin placebo for 10 ± 4 days

    Reporting group title
    Enoxaparin
    Reporting group description
    		 Daily subcutaneous (SQ) injections of enoxaparin for 10 ± 4 days and oral (PO) betrixaban placebo capsules for 35 to 42 days

    Reporting group values
    		 Betrixaban Enoxaparin Total
    Number of subjects
    		 3759 3754 7513
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 384 398 782
        From 65-84 years
    		 2767 2802 5569
        85 years and over
    		 608 554 1162
    Gender categorical
    Units: Subjects
        Female
    		 2054 2034 4088
        Male
    		 1705 1720 3425

    End points

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    End points reporting groups
    Reporting group title
    Betrixaban
    Reporting group description
    		 Daily oral (PO) betrixaban capsules for 35 to 42 days and subcutaneous (SQ) injections of enoxaparin placebo for 10 ± 4 days

    Reporting group title
    Enoxaparin
    Reporting group description
    		 Daily subcutaneous (SQ) injections of enoxaparin for 10 ± 4 days and oral (PO) betrixaban placebo capsules for 35 to 42 days

    Primary: Percentage of participants experiencing the composite event of symptomatic DVT, non-fatal PE, VTE-related death, or asymptomatic proximal DVT, through Visit 3

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    End point title
    		 Percentage of participants experiencing the composite event of symptomatic DVT, non-fatal PE, VTE-related death, or asymptomatic proximal DVT, through Visit 3
    End point description
    Percentage of participants experiencing either symptomatic DVT, non-fatal PE, VTE related death adjudicated by a blinded independent CEC between randomization and on or before Visit 3 or Day 42 if patient did not have a Visit 3, or a blinded ultrasound core laboratory measuring of asymptomatic proximal DVT between randomization and Day 47. Visit 3 is between day 35-42 after randomization (day 1).
    End point type
    Primary
    End point timeframe
    Between randomization and Day 47 (max)
    End point values
    		 Betrixaban Enoxaparin
    Number of subjects analysed
    1914
    1956
    Units: Number of Participants
        number (confidence interval 95%)
    6.90 (5.76 to 8.03)
    8.49 (7.25 to 9.72)
    Statistical analysis title
    		 Primary: Efficacy Endpoint
    Statistical analysis description
    Cohort 1 (participants with baseline D-dimer ≥ 2 x ULN as determined by the local lab) of the PEOP population which consisted of all participants who had taken at least one dose of study drug and who had follow-up assessment data on one or more primary or secondary efficacy components.
    Comparison groups
    Betrixaban v Enoxaparin
    Number of subjects included in analysis
    3870
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.054
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Relative Risk Reduction (RRR)
    Point estimate
    0.194
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.004
         upper limit
    		 0.353

    Primary: Percentage of participants experiencing the composite event of symptomatic DVT, non-fatal PE, VTE-related death, or asymptomatic proximal DVT, through Visit 3

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    End point title
    		 Percentage of participants experiencing the composite event of symptomatic DVT, non-fatal PE, VTE-related death, or asymptomatic proximal DVT, through Visit 3
    End point description
    Percentage of participants experiencing either symptomatic DVT, non-fatal PE, VTE related death adjudicated by a blinded independent CEC between randomization and on or before Visit 3 or Day 42 if patient did not have a Visit 3, or a blinded ultrasound core laboratory measuring of asymptomatic proximal DVT between randomization and Day 47. Visit 3 is between day 35-42 after randomization (day 1).
    End point type
    Primary
    End point timeframe
    Between randomization and Day 47 (max)
    End point values
    		 Betrixaban Enoxaparin
    Number of subjects analysed
    2842
    2893
    Units: Number of Participants
        number (confidence interval 95%)
    5.63 (4.78 to 6.48)
    7.05 (6.12 to 7.98)
    Statistical analysis title
    		 Primary: Efficacy Endpoint
    Statistical analysis description
    Cohort 2 (participants with baseline D-dimer ≥ 2 x ULN as determined by the local lab or age ≥ 75 years) of the PEOP population which consisted of all participants who had taken at least one dose of study drug and who had follow-up assessment data on one or more primary or secondary efficacy components.
    Comparison groups
    Betrixaban v Enoxaparin
    Number of subjects included in analysis
    5735
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.029
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Relative Risk Reduction (RRR)
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.023
         upper limit
    		 0.345

    Primary: Percentage of participants experiencing the composite event of symptomatic DVT, non-fatal PE, VTE-related death, or asymptomatic proximal DVT, through Visit 3

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    End point title
    		 Percentage of participants experiencing the composite event of symptomatic DVT, non-fatal PE, VTE-related death, or asymptomatic proximal DVT, through Visit 3
    End point description
    Percentage of participants experiencing either symptomatic DVT, non-fatal PE, VTE related death adjudicated by a blinded independent CEC between randomization and on or before Visit 3 or Day 42 if patient did not have a Visit 3, or a blinded ultrasound core laboratory measuring of asymptomatic proximal DVT between randomization and Day 47. Visit 3 is between day 35-42 after randomization (day 1).
    End point type
    Primary
    End point timeframe
    Between randomization and Day 47 (max)
    End point values
    		 Betrixaban Enoxaparin
    Number of subjects analysed
    3112
    3174
    Units: Number of Participants
        number (confidence interval 95%)
    5.30 (4.51 to 6.09)
    7.03 (6.14 to 7.91)
    Statistical analysis title
    		 Primary: Efficacy Endpoint
    Statistical analysis description
    The PEOP population which consisted of all participants who had taken at least one dose of study drug and who had follow-up assessment data on one or more primary or secondary efficacy components.
    Comparison groups
    Betrixaban v Enoxaparin
    Number of subjects included in analysis
    6286
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.006
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Relative Risk Reduction (RRR)
    Point estimate
    0.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.077
         upper limit
    		 0.375

    Primary: Percentage of participants experiencing major bleeding through seven days after discontinuation of all study medication

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    End point title
    		 Percentage of participants experiencing major bleeding through seven days after discontinuation of all study medication
    End point description
    Percentage of participants experiencing at least one major bleeding adjudicated by a blinded independent CEC between randomization (day 1) and up to seven days after discontinuation of all study medication.
    End point type
    Primary
    End point timeframe
    Between randomization and Day 49 (max)
    End point values
    		 Betrixaban Enoxaparin
    Number of subjects analysed
    3716
    3716
    Units: Number of Participants
        number (confidence interval 95%)
    0.67 (0.41 to 0.94)
    0.57 (0.32 to 0.81)
    Statistical analysis title
    		 Primary: Safety Analysis
    Statistical analysis description
    Safety population which consisted of all participants who had taken at least one dose of study drug.
    Comparison groups
    Betrixaban v Enoxaparin
    Number of subjects included in analysis
    7432
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.554
    Method
    		 Chi-squared
    Confidence interval

    Secondary: Percentage of participants experiencing the composite event of symptomatic DVT, non-fatal PE, or VTE-related death, through Visit 3

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    End point title
    		 Percentage of participants experiencing the composite event of symptomatic DVT, non-fatal PE, or VTE-related death, through Visit 3
    End point description
    Percentage of participants experiencing either symptomatic DVT, non-fatal PE, or VTE related death adjudicated by a blinded independent CEC between randomization and on or before Visit 3 or Day 42 if patient did not have a Visit 3. Visit 3 is between day 35-42 after randomization (day 1).
    End point type
    Secondary
    End point timeframe
    Between randomization and Day 42 (max)
    End point values
    		 Betrixaban Enoxaparin
    Number of subjects analysed
    2314
    2313
    Units: Number of Participants
        number (confidence interval 95%)
    1.30 (0.84 to 1.76)
    1.90 (1.35 to 2.46)
    Statistical analysis title
    		 Secondary: Efficacy Analysis
    Statistical analysis description
    Cohort 1 (participants with baseline D-dimer ≥ 2 x ULN as determined by the local lab) of the mITT population which consisted of all participants who had taken at least one dose of study drug and who had follow-up assessment data on one or more primary or secondary efficacy components.
    Comparison groups
    Betrixaban v Enoxaparin
    Number of subjects included in analysis
    4627
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.092
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Relative Risk Reduction (RRR)
    Point estimate
    0.326
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.069
         upper limit
    		 0.576

    Secondary: Percentage of participants experiencing the composite event of symptomatic DVT, non-fatal PE, or VTE-related death, through Visit 3

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    End point title
    		 Percentage of participants experiencing the composite event of symptomatic DVT, non-fatal PE, or VTE-related death, through Visit 3
    End point description
    Percentage of participants experiencing either symptomatic DVT, non-fatal PE, or VTE related death adjudicated by a blinded independent CEC between randomization and on or before Visit 3 or Day 42 if patient did not have a Visit 3. Visit 3 is between day 35-42 after randomization (day 1).
    End point type
    Secondary
    End point timeframe
    Between randomization and Day 42 (max)
    End point values
    		 Betrixaban Enoxaparin
    Number of subjects analysed
    3407
    3391
    Units: Number of Participants
        number (confidence interval 95%)
    1.03 (0.69 to 1.37)
    1.45 (1.04 to 1.85)
    Statistical analysis title
    		 Secondary: Efficacy Analysis
    Statistical analysis description
    Cohort 2 (participants with baseline D-dimer ≥ 2 x ULN as determined by the local lab or age ≥ 75 years) of the mITT population which consisted of all participants who had taken at least one dose of study drug and who had follow-up assessment data on one or more primary or secondary efficacy components.
    Comparison groups
    Betrixaban v Enoxaparin
    Number of subjects included in analysis
    6798
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.11
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Relative Risk Reduction (RRR)
    Point estimate
    0.295
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.085
         upper limit
    		 0.542

    Secondary: Percentage of participants experiencing the composite event of symptomatic DVT, non-fatal PE, or VTE-related death, through Visit 3

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    End point title
    		 Percentage of participants experiencing the composite event of symptomatic DVT, non-fatal PE, or VTE-related death, through Visit 3
    End point description
    Percentage of participants experiencing either symptomatic DVT, non-fatal PE, or VTE related death adjudicated by a blinded independent CEC between randomization and on or before Visit 3 or Day 42 if patient did not have a Visit 3. Visit 3 is between day 35-42 after randomization (day 1).
    End point type
    Secondary
    End point timeframe
    Between randomization and Day 42 (max)
    End point values
    		 Betrixaban Enoxaparin
    Number of subjects analysed
    3721
    3720
    Units: Number of Participants
        number (confidence interval 95%)
    0.94 (0.63 to 1.25)
    1.45 (1.07 to 1.84)
    Statistical analysis title
    		 Secondary: Efficacy Analysis
    Statistical analysis description
    The mITT population which consisted of all participants who had taken at least one dose of study drug and who had follow-up assessment data on one or more primary or secondary efficacy components.
    Comparison groups
    Betrixaban v Enoxaparin
    Number of subjects included in analysis
    7441
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.039
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Relative Risk Reduction (RRR)
    Point estimate
    0.358
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.02
         upper limit
    		 0.58

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose date (including) till the end of study
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Betrixaban
    Reporting group description
    		 Daily oral (PO) betrixaban capsules for 35 to 42 days and subcutaneous (SQ) injections of enoxaparin placebo for 10 ± 4 days

    Reporting group title
    Enoxaparin
    Reporting group description
    		 Daily subcutaneous (SQ) injections of enoxaparin for 10 ± 4 days and oral (PO) betrixaban placebo capsules for 35 to 42 days

    Serious adverse events
    		 Betrixaban Enoxaparin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    657 / 3716 (17.68%)
    615 / 3716 (16.55%)
         number of deaths (all causes)
    213
    214
         number of deaths resulting from adverse events
    206
    211
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lung neoplasm malignant
         subjects affected / exposed
    10 / 3716 (0.27%)
    8 / 3716 (0.22%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 8
         deaths causally related to treatment / all
    0 / 4
    0 / 4
    Cervix carcinoma
         subjects affected / exposed
    2 / 3716 (0.05%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    3 / 3716 (0.08%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Metastatic neoplasm
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cancer
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Rectal cancer
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenocarcinoma
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Brain neoplasm
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Breast cancer metastatic
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Bronchial carcinoma
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (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
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colorectal adenocarcinoma
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Colorectal cancer
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastrointestinal stromal tumour
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukaemia
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung carcinoma cell type unspecified stage IV
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant pleural effusion
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningioma
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to bone
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metastases to liver
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (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 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastasis
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Myeloid leukaemia
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasm malignant
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-Hodgkin's lymphoma
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal carcinoma
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (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 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Plasmacytoma
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural mesothelioma
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectosigmoid cancer
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Throat cancer
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vulval cancer
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    16 / 3716 (0.43%)
    38 / 3716 (1.02%)
         occurrences causally related to treatment / all
    0 / 16
    0 / 38
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    8 / 3716 (0.22%)
    3 / 3716 (0.08%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Haematoma
         subjects affected / exposed
    5 / 3716 (0.13%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    4 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 3716 (0.03%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 3716 (0.03%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic aneurysm
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic dissection
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic vasculitis
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    0 / 3716 (0.00%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aneurysm
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angiopathy
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Arterial disorder
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial stenosis
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bleeding varicose vein
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolism arterial
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Essential hypertension
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral artery aneurysm
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (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
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intra-abdominal haematoma
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemia
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery aneurysm
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Peripheral vascular disorder
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Phlebitis superficial
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Coronary artery bypass
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glaucoma surgery
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip arthroplasty
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hospitalisation
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hysterectomy
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leg amputation
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve repair
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgery
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (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
    Death
         subjects affected / exposed
    9 / 3716 (0.24%)
    16 / 3716 (0.43%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 16
         deaths causally related to treatment / all
    0 / 9
    0 / 16
    Sudden cardiac death
         subjects affected / exposed
    6 / 3716 (0.16%)
    5 / 3716 (0.13%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 6
    0 / 5
    Multi-organ failure
         subjects affected / exposed
    3 / 3716 (0.08%)
    6 / 3716 (0.16%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 6
    General physical health deterioration
         subjects affected / exposed
    6 / 3716 (0.16%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 5
    0 / 1
    Sudden death
         subjects affected / exposed
    3 / 3716 (0.08%)
    3 / 3716 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 3
    1 / 3
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 3716 (0.05%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    3 / 3716 (0.08%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac death
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Chest pain
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter site haemorrhage
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Condition aggravated
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device malfunction
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Discomfort
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibrosis
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised oedema
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperthermia
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injection site haemorrhage
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Necrosis
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (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 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Puncture site haemorrhage
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulcer
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaphylactic reaction
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (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
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Social circumstances
    Activities of daily living impaired
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervix haemorrhage uterine
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Genital haemorrhage
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (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
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    38 / 3716 (1.02%)
    43 / 3716 (1.16%)
         occurrences causally related to treatment / all
    0 / 41
    0 / 47
         deaths causally related to treatment / all
    0 / 8
    0 / 6
    Respiratory failure
         subjects affected / exposed
    30 / 3716 (0.81%)
    17 / 3716 (0.46%)
         occurrences causally related to treatment / all
    0 / 32
    1 / 17
         deaths causally related to treatment / all
    0 / 13
    1 / 7
    Pulmonary embolism
         subjects affected / exposed
    11 / 3716 (0.30%)
    26 / 3716 (0.70%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 26
         deaths causally related to treatment / all
    0 / 6
    0 / 10
    Acute respiratory failure
         subjects affected / exposed
    13 / 3716 (0.35%)
    9 / 3716 (0.24%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 10
         deaths causally related to treatment / all
    0 / 11
    0 / 4
    Epistaxis
         subjects affected / exposed
    10 / 3716 (0.27%)
    5 / 3716 (0.13%)
         occurrences causally related to treatment / all
    10 / 10
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    6 / 3716 (0.16%)
    4 / 3716 (0.11%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    Pulmonary fibrosis
         subjects affected / exposed
    3 / 3716 (0.08%)
    5 / 3716 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Pleural effusion
         subjects affected / exposed
    2 / 3716 (0.05%)
    5 / 3716 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    3 / 3716 (0.08%)
    3 / 3716 (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
    6 / 3716 (0.16%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    3 / 3716 (0.08%)
    3 / 3716 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute pulmonary oedema
         subjects affected / exposed
    3 / 3716 (0.08%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    2 / 3716 (0.05%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Chronic respiratory failure
         subjects affected / exposed
    1 / 3716 (0.03%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Haemoptysis
         subjects affected / exposed
    2 / 3716 (0.05%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    3 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    2 / 3716 (0.05%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Bronchiectasis
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis chronic
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    0 / 3716 (0.00%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 3716 (0.00%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    0 / 3716 (0.00%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    0 / 3716 (0.00%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Sleep apnoea syndrome
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alveolitis allergic
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial obstruction
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chylothorax
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Emphysema
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paranasal cyst
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax spontaneous
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary haemorrhage
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 3716 (0.00%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (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
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental disorder
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Hepatic enzyme increased
         subjects affected / exposed
    2 / 3716 (0.05%)
    5 / 3716 (0.13%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspiration bronchial
         subjects affected / exposed
    2 / 3716 (0.05%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical condition abnormal
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatine increased
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood urea increased
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood urine present
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheterisation cardiac
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Hip fracture
         subjects affected / exposed
    1 / 3716 (0.03%)
    3 / 3716 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    3 / 3716 (0.08%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 3716 (0.00%)
    3 / 3716 (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 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Accident
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Accidental overdose
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Latrogenic injury
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax traumatic
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural haemorrhage
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (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 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin injury
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord injury
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic fracture
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic haematoma
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    83 / 3716 (2.23%)
    66 / 3716 (1.78%)
         occurrences causally related to treatment / all
    0 / 85
    0 / 70
         deaths causally related to treatment / all
    0 / 30
    0 / 33
    Atrial fibrillation
         subjects affected / exposed
    11 / 3716 (0.30%)
    23 / 3716 (0.62%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 23
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    10 / 3716 (0.27%)
    15 / 3716 (0.40%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 17
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    Cardiac failure acute
         subjects affected / exposed
    10 / 3716 (0.27%)
    12 / 3716 (0.32%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 12
         deaths causally related to treatment / all
    0 / 3
    0 / 8
    Cardiac failure chronic
         subjects affected / exposed
    13 / 3716 (0.35%)
    9 / 3716 (0.24%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 11
         deaths causally related to treatment / all
    0 / 5
    0 / 2
    Acute myocardial infarction
         subjects affected / exposed
    6 / 3716 (0.16%)
    12 / 3716 (0.32%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 12
         deaths causally related to treatment / all
    0 / 4
    0 / 2
    Myocardial infarction
         subjects affected / exposed
    7 / 3716 (0.19%)
    10 / 3716 (0.27%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 10
         deaths causally related to treatment / all
    0 / 2
    0 / 5
    Cardiogenic shock
         subjects affected / exposed
    9 / 3716 (0.24%)
    6 / 3716 (0.16%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 6
         deaths causally related to treatment / all
    0 / 6
    0 / 5
    Cardiac arrest
         subjects affected / exposed
    7 / 3716 (0.19%)
    5 / 3716 (0.13%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 5
         deaths causally related to treatment / all
    0 / 5
    0 / 5
    Coronary artery disease
         subjects affected / exposed
    8 / 3716 (0.22%)
    3 / 3716 (0.08%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    3 / 3716 (0.08%)
    7 / 3716 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute coronary syndrome
         subjects affected / exposed
    6 / 3716 (0.16%)
    3 / 3716 (0.08%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    5 / 3716 (0.13%)
    3 / 3716 (0.08%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    2 / 3716 (0.05%)
    6 / 3716 (0.16%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Angina pectoris
         subjects affected / exposed
    5 / 3716 (0.13%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    3 / 3716 (0.08%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Cardiopulmonary failure
         subjects affected / exposed
    1 / 3716 (0.03%)
    4 / 3716 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    Ventricular tachycardia
         subjects affected / exposed
    4 / 3716 (0.11%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery insufficiency
         subjects affected / exposed
    2 / 3716 (0.05%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    1 / 3716 (0.03%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiovascular disorder
         subjects affected / exposed
    1 / 3716 (0.03%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Cardiovascular insufficiency
         subjects affected / exposed
    0 / 3716 (0.00%)
    3 / 3716 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    Ventricular fibrillation
         subjects affected / exposed
    1 / 3716 (0.03%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 3716 (0.00%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cor pulmonale
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Pericardial effusion
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sick sinus syndrome
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute left ventricular failure
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac ventricular thrombosis
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congestive cardiomyopathy
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial haemorrhage
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Sinoatrial block
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stress cardiomyopathy
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tricuspid valve incompetence
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Trifascicular block
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular hypokinesia
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Ischaemic stroke
         subjects affected / exposed
    19 / 3716 (0.51%)
    35 / 3716 (0.94%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 35
         deaths causally related to treatment / all
    0 / 6
    0 / 12
    Brain oedema
         subjects affected / exposed
    8 / 3716 (0.22%)
    10 / 3716 (0.27%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 10
         deaths causally related to treatment / all
    0 / 5
    0 / 9
    Cerebrovascular accident
         subjects affected / exposed
    7 / 3716 (0.19%)
    6 / 3716 (0.16%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 4
    Syncope
         subjects affected / exposed
    4 / 3716 (0.11%)
    4 / 3716 (0.11%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    3 / 3716 (0.08%)
    3 / 3716 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    2 / 3716 (0.05%)
    4 / 3716 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Convulsion
         subjects affected / exposed
    2 / 3716 (0.05%)
    3 / 3716 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    4 / 3716 (0.11%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    1 / 3716 (0.03%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Subarachnoid haemorrhage
         subjects affected / exposed
    1 / 3716 (0.03%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coma
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 3716 (0.00%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic transformation stroke
         subjects affected / exposed
    0 / 3716 (0.00%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebellar infarction
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cerebral ischaemia
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemic coma
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intraventricular haemorrhage
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorder
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Neuroglycopenia
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neurological decompensation
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paralysis flaccid
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyneuropathy
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Presyncope
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Unresponsive to stimuli
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    8 / 3716 (0.22%)
    4 / 3716 (0.11%)
         occurrences causally related to treatment / all
    2 / 8
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coagulopathy
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic anaemia
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polycythaemia
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spontaneous haematoma
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Conjunctival haemorrhage
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic retinopathy
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal haemorrhage
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastrointestinal haemorrhage
         subjects affected / exposed
    18 / 3716 (0.48%)
    5 / 3716 (0.13%)
         occurrences causally related to treatment / all
    14 / 18
    4 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    15 / 3716 (0.40%)
    3 / 3716 (0.08%)
         occurrences causally related to treatment / all
    11 / 15
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    2 / 3716 (0.05%)
    3 / 3716 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    3 / 3716 (0.08%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 3716 (0.03%)
    4 / 3716 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 3716 (0.03%)
    3 / 3716 (0.08%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 3716 (0.00%)
    4 / 3716 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 3716 (0.00%)
    3 / 3716 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Diarrhoea
         subjects affected / exposed
    1 / 3716 (0.03%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    2 / 3716 (0.05%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 3716 (0.03%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gingival bleeding
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal haemorrhage
         subjects affected / exposed
    0 / 3716 (0.00%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Melaena
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngo-oesophageal diverticulum
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal strangulated hernia
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Abdominal wall haematoma
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute abdomen
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer perforation
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroduodenal haemorrhage
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorder
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastrointestinal necrosis
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal polyp haemorrhage
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Large intestinal haemorrhage
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mechanical ileus
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic ulcer haemorrhage
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Volvulus
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    4 / 3716 (0.11%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bile duct stone
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatocellular injury
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic hepatitis
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Portal vein thrombosis
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin ulcer
         subjects affected / exposed
    3 / 3716 (0.08%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decubitus ulcer
         subjects affected / exposed
    0 / 3716 (0.00%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute generalised exanthematous pustulosis
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermatitis bullous
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ecchymosis
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pemphigoid
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Petechiae
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin disorder
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    10 / 3716 (0.27%)
    15 / 3716 (0.40%)
         occurrences causally related to treatment / all
    2 / 10
    1 / 15
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    Renal failure acute
         subjects affected / exposed
    12 / 3716 (0.32%)
    11 / 3716 (0.30%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Haematuria
         subjects affected / exposed
    17 / 3716 (0.46%)
    5 / 3716 (0.13%)
         occurrences causally related to treatment / all
    11 / 17
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure chronic
         subjects affected / exposed
    8 / 3716 (0.22%)
    4 / 3716 (0.11%)
         occurrences causally related to treatment / all
    1 / 9
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage urinary tract
         subjects affected / exposed
    2 / 3716 (0.05%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    3 / 3716 (0.08%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute prerenal failure
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis haemorrhagic
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glomerulonephritis rapidly progressive
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephropathy
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (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
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral haemorrhage
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Goitre
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoparathyroidism
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical spinal stenosis
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chondrocalcinosis
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coccydynia
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc degeneration
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteochondrosis
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polymyositis
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scleroderma
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Synovial cyst
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    46 / 3716 (1.24%)
    64 / 3716 (1.72%)
         occurrences causally related to treatment / all
    0 / 49
    0 / 66
         deaths causally related to treatment / all
    0 / 8
    0 / 15
    Urinary tract infection
         subjects affected / exposed
    13 / 3716 (0.35%)
    11 / 3716 (0.30%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    13 / 3716 (0.35%)
    7 / 3716 (0.19%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 7
         deaths causally related to treatment / all
    0 / 9
    0 / 2
    Septic shock
         subjects affected / exposed
    7 / 3716 (0.19%)
    8 / 3716 (0.22%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 8
         deaths causally related to treatment / all
    0 / 5
    0 / 5
    Cellulitis
         subjects affected / exposed
    3 / 3716 (0.08%)
    7 / 3716 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 3716 (0.03%)
    6 / 3716 (0.16%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    4 / 3716 (0.11%)
    3 / 3716 (0.08%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Erysipelas
         subjects affected / exposed
    4 / 3716 (0.11%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    4 / 3716 (0.11%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    2 / 3716 (0.05%)
    1 / 3716 (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
    1 / 3716 (0.03%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    1 / 3716 (0.03%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Infected skin ulcer
         subjects affected / exposed
    2 / 3716 (0.05%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lobar pneumonia
         subjects affected / exposed
    1 / 3716 (0.03%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pyelonephritis
         subjects affected / exposed
    2 / 3716 (0.05%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 3716 (0.03%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    2 / 3716 (0.05%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium colitis
         subjects affected / exposed
    0 / 3716 (0.00%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastrointestinal bacterial infection
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (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 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mastoiditis
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nosocomial infection
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oral candidiasis
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia staphylococcal
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia streptococcal
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomonal sepsis
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pseudomonas infection
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psoas abscess
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pyelocystitis
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (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 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (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
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (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
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomembranous colitis
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Abscess bacterial
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atypical pneumonia
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (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 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone abscess
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis bacterial
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridial infection
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (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
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocarditis bacterial
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Enterococcal infection
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gallbladder empyema
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (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
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 3716 (0.03%)
    3 / 3716 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 3716 (0.03%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    0 / 3716 (0.00%)
    2 / 3716 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    2 / 3716 (0.05%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 3716 (0.03%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hypercalcaemia
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypernatraemia
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperphosphataemia
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    0 / 3716 (0.00%)
    1 / 3716 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 1 diabetes mellitus
         subjects affected / exposed
    1 / 3716 (0.03%)
    0 / 3716 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 Betrixaban Enoxaparin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    879 / 3716 (23.65%)
    779 / 3716 (20.96%)
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    29 / 3716 (0.78%)
    58 / 3716 (1.56%)
         occurrences all number
    29
    59
    Hypertension
         subjects affected / exposed
    88 / 3716 (2.37%)
    80 / 3716 (2.15%)
         occurrences all number
    95
    86
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    50 / 3716 (1.35%)
    85 / 3716 (2.29%)
         occurrences all number
    53
    89
    Cardiac failure
         subjects affected / exposed
    48 / 3716 (1.29%)
    32 / 3716 (0.86%)
         occurrences all number
    49
    33
    Mitral valve incompetence
         subjects affected / exposed
    41 / 3716 (1.10%)
    49 / 3716 (1.32%)
         occurrences all number
    41
    49
    Tricuspid valve incompetence
         subjects affected / exposed
    38 / 3716 (1.02%)
    41 / 3716 (1.10%)
         occurrences all number
    38
    41
    Nervous system disorders
    Headache
         subjects affected / exposed
    74 / 3716 (1.99%)
    59 / 3716 (1.59%)
         occurrences all number
    77
    65
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    44 / 3716 (1.18%)
    29 / 3716 (0.78%)
         occurrences all number
    44
    35
    General disorders and administration site conditions
    Oedema peripheral
         subjects affected / exposed
    39 / 3716 (1.05%)
    19 / 3716 (0.51%)
         occurrences all number
    39
    19
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    109 / 3716 (2.93%)
    102 / 3716 (2.74%)
         occurrences all number
    114
    102
    Diarrhoea
         subjects affected / exposed
    63 / 3716 (1.70%)
    59 / 3716 (1.59%)
         occurrences all number
    68
    61
    Nausea
         subjects affected / exposed
    67 / 3716 (1.80%)
    55 / 3716 (1.48%)
         occurrences all number
    72
    57
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    53 / 3716 (1.43%)
    41 / 3716 (1.10%)
         occurrences all number
    55
    44
    Epistaxis
         subjects affected / exposed
    48 / 3716 (1.29%)
    19 / 3716 (0.51%)
         occurrences all number
    54
    19
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    87 / 3716 (2.34%)
    89 / 3716 (2.40%)
         occurrences all number
    90
    90
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    46 / 3716 (1.24%)
    23 / 3716 (0.62%)
         occurrences all number
    49
    25
    Renal cyst
         subjects affected / exposed
    55 / 3716 (1.48%)
    47 / 3716 (1.26%)
         occurrences all number
    55
    47
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    110 / 3716 (2.96%)
    78 / 3716 (2.10%)
         occurrences all number
    112
    84
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    91 / 3716 (2.45%)
    84 / 3716 (2.26%)
         occurrences all number
    100
    90

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    23 Apr 2012
    •Modification of Inclusion and Exclusion Criteria. •Addition of Day 4 of study procedures. •Modification of Statistical Considerations. •Additional clarifications, deletions and administrative corrections were made throughout the document and Appendices to improve clarity and consistency.
    15 Feb 2013
    •Modification of Inclusion and Exclusion Criteria. •Addition of a Post Randomization Dose Reductions. •Modification of Statistical Considerations. •Additional clarifications, deletions and administrative corrections were made throughout the document and Appendices to improve clarity and consistency.
    04 Jun 2014
    •Modification of Inclusion and Exclusion Criteria to exclude enrollment of patients in the biomarker negative subgroup (age <75 and D-dimer <2x ULN) •Modification of Statistical Considerations. •Modification to Outcome Adjudication and Definitions to align with modifications to the Clinical Events Committee (CEC) Charter •Additional clarifications, deletions and administrative corrections were made throughout the document and Appendices to improve clarity and consistency.
    28 Jan 2016
    •Update to Statistical Analysis

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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