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    Clinical Trial Results:
    PeriOperative ISchemic Evaluation-3 (POISE-3) Trial

    Summary
    EudraCT number
    		 2018-000539-29
    Trial protocol
    		 BE   DK   AT   NL   IT  
    Global end of trial date
    03 Feb 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Feb 2025
    First version publication date
    15 Feb 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    2018.02.08
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03505723
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Population Health Research Institute
    Sponsor organisation address
    20 Copeland Avenue, Hamilton, Canada,
    Public contact
    POISE-3 Project Office, Population Health Research Institute, 001 905-521-2100x4063, poise3@phri.ca
    Scientific contact
    POISE-3 Project Office, Population Health Research Institute, 001 905-521-2100x4063, poise3@phri.ca
    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
    28 Feb 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    08 Nov 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Feb 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine if TXA is superior to placebo for the occurrence of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events; and to determine the impact of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major vascular events in patients who are followed for 30 days after noncardiac surgery.
    Protection of trial subjects
    An independent data and safety monitoring committee reviewed interim analyses when 25%, 50%, and 75% of the 30-day data were available.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Jun 2018
    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
    Netherlands: 172
    Country: Number of subjects enrolled
    Poland: 143
    Country: Number of subjects enrolled
    Spain: 753
    Country: Number of subjects enrolled
    United Kingdom: 76
    Country: Number of subjects enrolled
    Austria: 84
    Country: Number of subjects enrolled
    Belgium: 152
    Country: Number of subjects enrolled
    Denmark: 130
    Country: Number of subjects enrolled
    France: 7
    Country: Number of subjects enrolled
    Germany: 133
    Country: Number of subjects enrolled
    Italy: 284
    Country: Number of subjects enrolled
    Australia: 573
    Country: Number of subjects enrolled
    Brazil: 71
    Country: Number of subjects enrolled
    Canada: 1916
    Country: Number of subjects enrolled
    Chile: 107
    Country: Number of subjects enrolled
    China: 425
    Country: Number of subjects enrolled
    India: 631
    Country: Number of subjects enrolled
    Malaysia: 654
    Country: Number of subjects enrolled
    New Zealand: 167
    Country: Number of subjects enrolled
    Pakistan: 128
    Country: Number of subjects enrolled
    Russian Federation: 1859
    Country: Number of subjects enrolled
    South Africa: 25
    Country: Number of subjects enrolled
    United States: 1045
    Worldwide total number of subjects
    9535
    EEA total number of subjects
    1858
    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)
    2790
    From 65 to 84 years
    6314
    85 years and over
    431

    Subject disposition

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    Recruitment
    Recruitment details
    		 We recruited patients from June 2018 through July 2021 at 114 hospitals in 22 countries. We randomly assigned 9535 patients to receive tranexamic acid (4757 patients) or placebo (4778 patients) The 30-day follow-up visit was completed for 99.9% of the patients.

    Pre-assignment
    Screening details
    		 26,581 were screened and eligible patients. Out of this number 17,046 eligible patients were not randomized. 5970 Patients did not consent; 3544 Physician declined to have patient participate; 4453 Research or staff unavailable; 925 not eligible for BP management arm; 520 Language barrier and 1634 were classified as other.

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst
    Blinding implementation details
    Randomization was performed by a central computerized system with the use of block randomization, with stratification according to center. Patients were assigned in a 1:1 ratio to receive tranexamic acid or placebo at the start and end of surgery and, in a 1:1 ratio with the use of a partial factorial design, to a hypotension-avoidance strategy or a hypertension-avoidance strategy. Patients, providers, data collectors, and outcome adjudicators were unaware of the trial-group assignments.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Tranexamic acid (active)
    Arm description
    		 1g bolus/infusion within 20 minutes preceding anticipated skin incision, 1g bolus/infusion at surgery end when closing the wound
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Tranexamic acid (active)
    Investigational medicinal product code
    Other name
    TXA
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Intravenous bolus use
    Dosage and administration details
    1g bolus/infusion within 20 minutes preceding anticipated skin incision, 1g bolus/infusion at surgery end when closing the wound

    Arm title
    		 Tranexamic acid (placebo)
    Arm description
    		 0.9% normal saline bolus/infusion within 20 minutes preceding anticipated skin incision, at surgery end when closing the wound
    Arm type
    		 Placebo

    Investigational medicinal product name
    Tranexamic acid (placebo)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection/infusion
    Routes of administration
    Intravenous bolus use
    Dosage and administration details
    0.9% normal saline bolus/infusion within 20 minutes preceding anticipated skin incision, at surgery end when closing the wound

    Number of subjects in period 1
    		Tranexamic acid (active) Tranexamic acid (placebo)
    Started
    4757
    4778
    Completed
    4757
    4778

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Tranexamic acid (active)
    Reporting group description
    		 1g bolus/infusion within 20 minutes preceding anticipated skin incision, 1g bolus/infusion at surgery end when closing the wound

    Reporting group title
    Tranexamic acid (placebo)
    Reporting group description
    		 0.9% normal saline bolus/infusion within 20 minutes preceding anticipated skin incision, at surgery end when closing the wound

    Reporting group values
    		 Tranexamic acid (active) Tranexamic acid (placebo) Total
    Number of subjects
    		 4757 4778 9535
    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)
    		 1387 1403 2790
        From 65-84 years
    		 3140 3174 6314
        85 years and over
    		 230 201 431
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 69.49 ( 9.45 ) 69.29 ( 9.36 ) -
    Gender categorical
    Units: Subjects
        Female
    		 2088 2097 4185
        Male
    		 2669 2681 5350
    Eligibility criteria met: History of coronary artery disease
    Units: Subjects
        Yes
    		 1410 1466 2876
        No
    		 3347 3312 6659
    Eligibility criteria met: History of peripheral artery disease
    Units: Subjects
        Yes
    		 714 722 1436
        No
    		 4043 4056 8099
    Eligibility criteria met: History of stroke
    Units: Subjects
        Yes
    		 400 388 788
        No
    		 4357 4390 8747
    Eligibility criteria met: Undergoing major vascular surgery
    Units: Subjects
        Yes
    		 541 544 1085
        No
    		 4216 4234 8450
    Risk criteria: Met ≥3 of 9 criteria
    Units: Subjects
        Yes
    		 3988 4003 7991
        No
    		 769 775 1544
    Risk criteria: Undergoing major surgery
    Units: Subjects
        Yes
    		 3741 3798 7539
        No
    		 1016 980 1996
    Risk criteria: Undergoing urgent or emergency surgery
    Units: Subjects
        Yes
    		 555 540 1095
        No
    		 4202 4238 8440
    Risk criteria: Age ≥70 yr
    Units: Subjects
        Yes
    		 2611 2588 5199
        No
    		 2146 2190 4336
    Risk criteria: Current diabetes for which medication is taken
    Units: Subjects
        Yes
    		 1749 1812 3561
        No
    		 3008 2966 5974
    Risk criteria: Preoperative serum creatinine level >175 μmol/liter
    Units: Subjects
        Yes
    		 57 73 130
        No
    		 4700 4705 9405
    Risk criteria: History of congestive heart failure
    Units: Subjects
        Yes
    		 674 671 1345
        No
    		 4083 4107 8190
    Risk criteria: History of transient ischemic attack
    Units: Subjects
        Yes
    		 282 247 529
        No
    		 4475 4531 9006
    Risk criteria: History of hypertension
    Units: Subjects
        Yes
    		 4293 4321 8614
        No
    		 464 457 921
    Risk criteria: History of smoking within 2 yr before surgery
    Units: Subjects
        Yes
    		 1131 1128 2259
        No
    		 3626 3650 7276
    Other medical history: Atrial fibrillation
    Units: Subjects
        Yes
    		 478 445 923
        No
    		 4279 4333 8612
    Other medical history: Active cancer
    Units: Subjects
        Yes
    		 1311 1360 2671
        No
    		 3446 3418 6864

    End points

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    End points reporting groups
    Reporting group title
    Tranexamic acid (active)
    Reporting group description
    		 1g bolus/infusion within 20 minutes preceding anticipated skin incision, 1g bolus/infusion at surgery end when closing the wound

    Reporting group title
    Tranexamic acid (placebo)
    Reporting group description
    		 0.9% normal saline bolus/infusion within 20 minutes preceding anticipated skin incision, at surgery end when closing the wound

    Primary: Primary End Point

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    End point title
    		 Primary End Point
    End point description
    End point type
    Primary
    End point timeframe
    >
    End point values
    		 Tranexamic acid (active) Tranexamic acid (placebo)
    Number of subjects analysed
    4757
    4778
    Units: Subjects
        Primary efficacy outcome: composite bleeding
    433
    561
        Primary safety outcome: composite cardiovascular
    649
    639
        MINS
    608
    602
        Nonhemorrhagic stroke
    24
    16
        Peripheral arterial thrombosis
    22
    23
        Symptomatic proximal venous thromboembolism
    32
    28
    Statistical analysis title
    		 Primary efficacy outcome
    Statistical analysis description
    Composite bleeding outcome
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 0.87
    Statistical analysis title
    		 Primary safety outcome
    Statistical analysis description
    Composite cardiovascular outcome
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.04
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 1.14
    Statistical analysis title
    		 Components of composite cardiovascular outcome 1
    Statistical analysis description
    Individual components of composite cardiovascular outcome: MINS
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.91
         upper limit
    		 1.14
    Statistical analysis title
    		 Components of composite cardiovascular outcome 2
    Statistical analysis description
    Individual components of composite cardiovascular outcome: Nonhemorrhagic stroke
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 2.84
    Statistical analysis title
    		 Components of composite cardiovascular outcome 3
    Statistical analysis description
    Individual components of composite cardiovascular outcome: Peripheral arterial thrombosis
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.53
         upper limit
    		 1.72
    Statistical analysis title
    		 Components of composite cardiovascular outcome 4
    Statistical analysis description
    Individual components of composite cardiovascular outcome: Symptomatic proximal venous thromboembolism
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 1.91

    Secondary: Secondary End Point

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    End point title
    		 Secondary End Point
    End point description
    End point type
    Secondary
    End point timeframe
    >
    End point values
    		 Tranexamic acid (active) Tranexamic acid (placebo)
    Number of subjects analysed
    4757
    4778
    Units: Subjects
        Bleeding independently assoc w death after NC Surg
    416
    541
        MINS not fulfilling the universal def of MI
    549
    549
        Myocardial infarction
    67
    53
        Net risk–benefit outcome
    983
    1046
        Life-threatening bleeding
    78
    79
        Major bleeding
    363
    496
        Bleeding into a critical organ
    12
    21
    Statistical analysis title
    		 Other secondary outcomes 1
    Statistical analysis description
    Bleeding independently associated with death after noncardiac surgery
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 0.87
    Statistical analysis title
    		 Other secondary outcomes 2
    Statistical analysis description
    MINS not fulfilling the universal definition of myocardial infarction
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.89
         upper limit
    		 1.13
    Statistical analysis title
    		 Other secondary outcomes 3
    Statistical analysis description
    Myocardial infarction
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.89
         upper limit
    		 1.82
    Statistical analysis title
    		 Other secondary outcomes 4
    Statistical analysis description
    Net risk–benefit outcome
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.86
         upper limit
    		 1.02
    Statistical analysis title
    		 Indiv. components of composite bleeding outcome 1
    Statistical analysis description
    Life-threatening bleeding
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 1.36
    Statistical analysis title
    		 Indiv. components of composite bleeding outcome 1
    Statistical analysis description
    Major bleeding
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 0.83
    Statistical analysis title
    		 Indiv. components of composite bleeding outcome 3
    Statistical analysis description
    Bleeding into a critical organ
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.28
         upper limit
    		 1.16

    Other pre-specified: Tertiary Outcomes

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    End point title
    		 Tertiary Outcomes
    End point description
    End point type
    Other pre-specified
    End point timeframe
    >
    End point values
    		 Tranexamic acid (active) Tranexamic acid (placebo)
    Number of subjects analysed
    4757
    4778
    Units: Subjects
        Major bleeding according to ISTH criteria
    315
    415
        Transfusion of ≥1 unit of packed red cells
    449
    574
        Death from any cause
    52
    57
        Death from cardiovascular cause
    25
    30
        Hemorrhagic stroke
    2
    0
        Amputation
    14
    21
        Symptomatic pulmonary embolism
    24
    17
        Symptomatic proximal deep venous thrombosis
    11
    13
        (a)symptomatic proximal venous thromboembolism
    32
    28
        Cardiac revascularization
    12
    13
        Acute kidney injury
    672
    655
        New renal-replacement therapy
    19
    16
        Rehospitalization for cardiovascular reasons
    84
    75
        Seizure
    10
    3
        Infection
    499
    487
        Sepsis
    68
    63
        Disability
    1408
    1407
    Statistical analysis title
    		 Tertiary outcome 1
    Statistical analysis description
    Major bleeding according to ISTH criteria
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.65
         upper limit
    		 0.87
    Statistical analysis title
    		 Tertiary outcome 2
    Statistical analysis description
    Transfusion of ≥1 unit of packed red cells
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 0.88
    Statistical analysis title
    		 Tertiary outcome 3
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 1.33
    Statistical analysis title
    		 Tertiary outcome 4
    Statistical analysis description
    Death from cardiovascular cause
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.49
         upper limit
    		 1.42
    Statistical analysis title
    		 Tertiary outcome 6
    Statistical analysis description
    Amputation
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.34
         upper limit
    		 1.31
    Statistical analysis title
    		 Tertiary outcome 7
    Statistical analysis description
    Symptomatic pulmonary embolism
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 2.64
    Statistical analysis title
    		 Tertiary outcome 8
    Statistical analysis description
    Symptomatic proximal deep venous thrombosis
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.38
         upper limit
    		 1.9
    Statistical analysis title
    		 Tertiary outcome 9
    Statistical analysis description
    Any symptomatic or asymptomatic proximal venous thromboembolism
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 1.91
    Statistical analysis title
    		 Tertiary outcome 10
    Statistical analysis description
    Cardiac revascularization
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 2.03
    Statistical analysis title
    		 Tertiary outcome 11
    Statistical analysis description
    Acute kidney injury
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.93
         upper limit
    		 1.15
    Statistical analysis title
    		 Tertiary outcome 13
    Statistical analysis description
    Rehospitalization for cardiovascular reasons
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 1.54
    Statistical analysis title
    		 Tertiary outcome 14
    Statistical analysis description
    Seizure
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    3.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 12.2
    Statistical analysis title
    		 Tertiary outcome 15
    Statistical analysis description
    Infection
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.91
         upper limit
    		 1.17
    Statistical analysis title
    		 Tertiary outcome 16
    Statistical analysis description
    Sepsis
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 1.53
    Statistical analysis title
    		 Tertiary outcome 19
    Statistical analysis description
    Disability
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 1.13
    Statistical analysis title
    		 Tertiary outcome 12
    Statistical analysis description
    New renal-replacement therapy
    Comparison groups
    Tranexamic acid (active) v Tranexamic acid (placebo)
    Number of subjects included in analysis
    9535
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.61
         upper limit
    		 2.32

    Adverse events

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    Adverse events information [1]
    Timeframe for reporting adverse events
    There are no non-serious adverse events recorded for these results.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27
    Reporting groups
    Reporting group title
    Tranexamic acid (active)
    Reporting group description
    		 1g bolus/infusion within 20 minutes preceding anticipated skin incision, 1g bolus/infusion at surgery end when closing the wound

    Reporting group title
    Placebo (active)
    Reporting group description
    		 0.9% normal saline bolus/infusion within 20 minutes preceding anticipated skin incision, at surgery end when closing the wound

    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: Given the well-established safety profile of the study drug and the primary focus on evaluating serious adverse events, this clinical trial did not systematically collect data on non-serious adverse events, as they are unlikely to provide significant information regarding the drug's safety concerns in this study population.
    Serious adverse events
    		 Tranexamic acid (active) Placebo (active)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    263 / 4757 (5.53%)
    242 / 4778 (5.06%)
         number of deaths (all causes)
    52
    57
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma gastric
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    B-cell lymphoma
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    3 / 4757 (0.06%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial carcinoma
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic myelomonocytic leukemia
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (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
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometrial cancer
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngeal cancer
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    1 / 4757 (0.02%)
    3 / 4778 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to lung
         subjects affected / exposed
    0 / 4757 (0.00%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasm
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (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 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal cancer
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of the hypopharynx
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adrenal gland cancer metastatic
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain neoplasm
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastatic neoplasm
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colorectal cancer
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (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
    1 / 4757 (0.02%)
    3 / 4778 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thyroid cancer stage I
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intraductal proliferative breast lesion
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Papillary renal cell carcinoma
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenocarcinoma metastatic
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hematoma
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    5 / 4757 (0.11%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    1 / 4757 (0.02%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    4 / 4757 (0.08%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    2 / 4757 (0.04%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischemia
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vena cava thrombosis
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dry gangrene
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemodynamic instability
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic occlusion
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brachiocephalic vein thrombosis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphatic fistula
         subjects affected / exposed
    2 / 4757 (0.04%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Granulomatosis with polyangiitis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral venous disease
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subclavian vein stenosis
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atheroembolism
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Pituitary tumor removal
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sarcoma excision
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal anastomosis
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal resection
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transurethral prostatectomy
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrostomy
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteral stent removal
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter placement
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter removal
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileocolostomy
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal anastomosis
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hernia repair
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         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
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Central venous catheter removal
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drain removal
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eventration repair
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalized edema
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hernia
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Edema
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Edema peripheral
         subjects affected / exposed
    2 / 4757 (0.04%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    4 / 4757 (0.08%)
    5 / 4778 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Swelling
         subjects affected / exposed
    0 / 4757 (0.00%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyp
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Medical device site discharge
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stenosis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehiscence
         subjects affected / exposed
    2 / 4757 (0.04%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         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
    Ovarian cyst
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Female genital tract fistula
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    2 / 4757 (0.04%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atelectasis
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    3 / 4757 (0.06%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnea
         subjects affected / exposed
    3 / 4757 (0.06%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemoptysis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    2 / 4757 (0.04%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 4757 (0.00%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngeal edema
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    5 / 4757 (0.11%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    4 / 4757 (0.08%)
    4 / 4778 (0.08%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory acidosis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory depression
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    2 / 4757 (0.04%)
    5 / 4778 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    2 / 4757 (0.04%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Negative pressure pulmonary edema
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    4 / 4757 (0.08%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device leakage
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device dislocation
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device occlusion
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device loosening
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Autoimmune hepatitis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bile duct stone
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary colic
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    4 / 4757 (0.08%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis alcoholic
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Portal vein thrombosis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver injury
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary obstruction
         subjects affected / exposed
    0 / 4757 (0.00%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood glucose increased
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood pressure abnormal
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood glucose fluctuation
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ejection fraction decreased
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coagulation test abnormal
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nutritional condition abnormal
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SARS-CoV-2 test positive
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Burns third degree
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    5 / 4757 (0.11%)
    3 / 4778 (0.06%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    2 / 4757 (0.04%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    2 / 4757 (0.04%)
    3 / 4778 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         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
    0 / 4757 (0.00%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple fractures
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peroneal nerve injury
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seroma
         subjects affected / exposed
    1 / 4757 (0.02%)
    3 / 4778 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric injury
         subjects affected / exposed
    0 / 4757 (0.00%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    6 / 4757 (0.13%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suture rupture
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anastomotic leak
         subjects affected / exposed
    3 / 4757 (0.06%)
    4 / 4778 (0.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prescribed overdose
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound complication
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative ileus
         subjects affected / exposed
    37 / 4757 (0.78%)
    30 / 4778 (0.63%)
         occurrences causally related to treatment / all
    0 / 37
    0 / 30
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural diarrhea
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound complication
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    1 / 4757 (0.02%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural hypotension
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic leak
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dural tear
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incision site inflammation
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal stoma complication
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal anastomotic leak
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiation sickness syndrome
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periprosthetic fracture
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic lung injury
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fascial rupture
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative delirium
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scrotal injury
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incarcerated parastomal hernia
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diversion colitis
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    11-beta-hydroxylase deficiency
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheo-esophageal fistula
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycinemia
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    2 / 4757 (0.04%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (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
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nodal arrhythmia
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 4757 (0.00%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Carotid artery thrombosis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrospinal fluid leakage
         subjects affected / exposed
    1 / 4757 (0.02%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dementia
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycemic encephalopathy
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peroneal nerve palsy
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    7 / 4757 (0.15%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxic encephalopathy
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischemic attack
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Visual field defect
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vocal cord paralysis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical radiculopathy
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anemia
         subjects affected / exposed
    2 / 4757 (0.04%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency anemia
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Amaurosis fugax
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blindness transient
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    6 / 4757 (0.13%)
    5 / 4778 (0.10%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal stenosis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    4 / 4757 (0.08%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhea
         subjects affected / exposed
    2 / 4757 (0.04%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal obstruction
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocele
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Food poisoning
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric polyps
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer perforation
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal fistula
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal hemorrhage
         subjects affected / exposed
    2 / 4757 (0.04%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hematemesis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileal stenosis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 4757 (0.02%)
    3 / 4778 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired gastric emptying
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal ischemia
         subjects affected / exposed
    2 / 4757 (0.04%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    10 / 4757 (0.21%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal pseudo-obstruction
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal stenosis
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malabsorption
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mesenteric artery thrombosis
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstruction gastric
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Esophageal stenosis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Esophagitis
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    2 / 4757 (0.04%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal prolapse
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    13 / 4757 (0.27%)
    3 / 4778 (0.06%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal perforation
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal hemorrhage
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumoperitoneum
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocutaneous fistula
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal edema
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incarcerated umbilical hernia
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngo-esophageal diverticulum
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intra-abdominal fluid collection
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal stenosis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal hemorrhage
         subjects affected / exposed
    1 / 4757 (0.02%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Decubitus ulcer
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous emphysema
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient acantholytic dermatosis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Hematuria
         subjects affected / exposed
    2 / 4757 (0.04%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (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
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 4757 (0.02%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric stenosis
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary bladder hemorrhage
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    7 / 4757 (0.15%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tubulointerstitial nephritis
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinoma
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal mass
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    16 / 4757 (0.34%)
    9 / 4778 (0.19%)
         occurrences causally related to treatment / all
    0 / 16
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    3 / 4757 (0.06%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    3 / 4757 (0.06%)
    5 / 4778 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Compartment syndrome
         subjects affected / exposed
    0 / 4757 (0.00%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fistula
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemarthrosis
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint effusion
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle atrophy
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 4757 (0.00%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    2 / 4757 (0.04%)
    3 / 4778 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudarthrosis
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc degeneration
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal stenosis
         subjects affected / exposed
    2 / 4757 (0.04%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abscess
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    3 / 4757 (0.06%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 4757 (0.00%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes simplex encephalitis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronavirus infection
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Abnormal loss of weight
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    2 / 4757 (0.04%)
    6 / 4778 (0.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         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
    2 / 4757 (0.04%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    0 / 4757 (0.00%)
    2 / 4778 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycemia
         subjects affected / exposed
    3 / 4757 (0.06%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalemia
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycemia
         subjects affected / exposed
    1 / 4757 (0.02%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalemia
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatremia
         subjects affected / exposed
    3 / 4757 (0.06%)
    7 / 4778 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycemic hyperosmolar nonketotic syndrome
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic metabolic decompensation
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Feeding intolerance
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adult failure to thrive
         subjects affected / exposed
    1 / 4757 (0.02%)
    0 / 4778 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Starvation ketoacidosis
         subjects affected / exposed
    0 / 4757 (0.00%)
    1 / 4778 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Tranexamic acid (active) Placebo (active)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 4757 (0.00%)
    0 / 4778 (0.00%)

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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