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    The EU Clinical Trials Register currently displays   41229   clinical trials with a EudraCT protocol, of which   6756   are clinical trials conducted with subjects less than 18 years old.
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    Clinical Trial Results:
    A Randomized, Double-blind, Double-dummy, Active-controlled, Parallel-group, Multicenter Study to Compare the Safety of Rivaroxaban versus Acetylsalicylic Acid in Addition to Either Clopidogrel or Ticagrelor Therapy in Subjects with Acute Coronary Syndrome

    Summary
    EudraCT number
    2014-004266-26
    Trial protocol
    BE   SE   CZ   NL   HU   ES   IT   BG   DK  
    Global end of trial date
    14 Oct 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    27 Oct 2017
    First version publication date
    27 Oct 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    RIVAROXACS2002
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02293395
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Janssen Research & Development, LLC
    Sponsor organisation address
    920 Highway 202 S, Raritan, NJ, United States, 08869
    Public contact
    Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
    Scientific contact
    Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    14 Oct 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Oct 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of the study was to estimate the bleeding risk with rivaroxaban, compared with acetyl salicylic acid (ASA), in addition to a single antiplatelet P2Y12 inhibitor agent (clopidogrel or ticagrelor), in subjects with a recent acute coronary syndrome (ACS) (including ST-segment elevation myocardial infarction [STEMI] and non-ST-segment elevation acute coronary syndrome [NSTE-ACS]).
    Protection of trial subjects
    The safety evaluations included bleeding events, other adverse events, and clinical laboratory tests (hematology and clinical chemistry) that were relevant and clinically meaningful to a serious adverse event (SAE) or endpoint event. Safety data obtained during the study were reviewed on a routine basis by an unblinded, independent data monitoring committee (IDMC). This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    22 Apr 2015
    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
    Spain: 122
    Country: Number of subjects enrolled
    Sweden: 79
    Country: Number of subjects enrolled
    Turkey: 200
    Country: Number of subjects enrolled
    Ukraine: 266
    Country: Number of subjects enrolled
    United States: 181
    Country: Number of subjects enrolled
    Argentina: 131
    Country: Number of subjects enrolled
    Australia: 35
    Country: Number of subjects enrolled
    Belgium: 89
    Country: Number of subjects enrolled
    Brazil: 162
    Country: Number of subjects enrolled
    Bulgaria: 161
    Country: Number of subjects enrolled
    Canada: 84
    Country: Number of subjects enrolled
    Czech Republic: 71
    Country: Number of subjects enrolled
    Denmark: 3
    Country: Number of subjects enrolled
    France: 57
    Country: Number of subjects enrolled
    Hungary: 201
    Country: Number of subjects enrolled
    Italy: 134
    Country: Number of subjects enrolled
    Japan: 59
    Country: Number of subjects enrolled
    Korea, Republic of: 54
    Country: Number of subjects enrolled
    Netherlands: 134
    Country: Number of subjects enrolled
    Poland: 333
    Country: Number of subjects enrolled
    Russian Federation: 481
    Worldwide total number of subjects
    3037
    EEA total number of subjects
    1384
    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)
    1776
    From 65 to 84 years
    1250
    85 years and over
    11

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 3,145 subjects were screened for eligibility, of these 108 subjects were screening failures and the remaining 3,037 subjects were randomized.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Rivaroxaban 2.5 mg Twice Daily (BID)
    Arm description
    Subjects received oral dose of 2.5 milligram (mg) rivaroxaban BID and Acetylsalicylic acid (ASA) placebo once daily (OD) along with either clopidogrel 75 mg OD or ticagrelor 90 mg BID for a minimum of 180 days, and up to 360 days of treatment.
    Arm type
    Experimental

    Investigational medicinal product name
    Rivaroxaban
    Investigational medicinal product code
    BAY59-7939
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received oral dose of 2.5 mg rivaroxaban BID for a minimum of 180 days, and up to 360 days of treatment.

    Investigational medicinal product name
    ASA Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received oral dose of placebo matching to 100 mg ASA OD along with either clopidogrel 75 mg OD or ticagrelor 90 mg BID for a minimum of 180 days, and up to 360 days of treatment.

    Arm title
    Acetylsalicylic acid 100 mg Once Daily (OD)
    Arm description
    Subjects received oral dose of 100 mg ASA OD and rivaroxaban placebo BID along with either clopidogrel 75 mg OD or ticagrelor 90 mg BID for a minimum of 180 days, and up to 360 days of treatment.
    Arm type
    Active comparator

    Investigational medicinal product name
    Rivaroxaban Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received oral dose of placebo matching to 2.5 mg rivaroxaban BID along with either clopidogrel 75 mg OD or ticagrelor 90 mg BID for a minimum of 180 days, and up to 360 days of treatment.

    Investigational medicinal product name
    Acetylsalicylic acid
    Investigational medicinal product code
    Other name
    Aspirin
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received oral dose of 100 mg ASA OD for a minimum of 180 days, and up to 360 days of treatment.

    Number of subjects in period 1
    Rivaroxaban 2.5 mg Twice Daily (BID) Acetylsalicylic acid 100 mg Once Daily (OD)
    Started
    1519
    1518
    Treated
    1510
    1506 [1]
    Completed
    1510
    1511
    Not completed
    9
    7
         Consent withdrawn by subject
    8
    7
         Lost to follow-up
    1
    -
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: To provide more clarification for the subjects who were treated and to justify safety analysis population, we have created a milestone in subject disposition as "Treated".

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Rivaroxaban 2.5 mg Twice Daily (BID)
    Reporting group description
    Subjects received oral dose of 2.5 milligram (mg) rivaroxaban BID and Acetylsalicylic acid (ASA) placebo once daily (OD) along with either clopidogrel 75 mg OD or ticagrelor 90 mg BID for a minimum of 180 days, and up to 360 days of treatment.

    Reporting group title
    Acetylsalicylic acid 100 mg Once Daily (OD)
    Reporting group description
    Subjects received oral dose of 100 mg ASA OD and rivaroxaban placebo BID along with either clopidogrel 75 mg OD or ticagrelor 90 mg BID for a minimum of 180 days, and up to 360 days of treatment.

    Reporting group values
    Rivaroxaban 2.5 mg Twice Daily (BID) Acetylsalicylic acid 100 mg Once Daily (OD) Total
    Number of subjects
    1519 1518 3037
    Title for AgeCategorical
    Units: subjects
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    887 889 1776
        From 65 to 84 years
    627 623 1250
        85 years and over
    5 6 11
    Title for AgeContinuous
    Units: years
        arithmetic mean (standard deviation)
    62.7 ± 9.14 62.9 ± 8.82 -
    Title for Gender
    Units: subjects
        Female
    385 377 762
        Male
    1134 1141 2275

    End points

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    End points reporting groups
    Reporting group title
    Rivaroxaban 2.5 mg Twice Daily (BID)
    Reporting group description
    Subjects received oral dose of 2.5 milligram (mg) rivaroxaban BID and Acetylsalicylic acid (ASA) placebo once daily (OD) along with either clopidogrel 75 mg OD or ticagrelor 90 mg BID for a minimum of 180 days, and up to 360 days of treatment.

    Reporting group title
    Acetylsalicylic acid 100 mg Once Daily (OD)
    Reporting group description
    Subjects received oral dose of 100 mg ASA OD and rivaroxaban placebo BID along with either clopidogrel 75 mg OD or ticagrelor 90 mg BID for a minimum of 180 days, and up to 360 days of treatment.

    Primary: Number of Subjects with non Coronary Artery Bypass Graft-Related (non CABG-related) Thrombolysis in Myocardial Infarction (TIMI) Clinically Significant Bleeding Events

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    End point title
    Number of Subjects with non Coronary Artery Bypass Graft-Related (non CABG-related) Thrombolysis in Myocardial Infarction (TIMI) Clinically Significant Bleeding Events
    End point description
    Non CABG-related TIMI clinically significant bleeding events are sum of non CABG-related TIMI major bleeding events, TIMI minor bleeding events and TIMI bleeding events requiring medical attention. Major: any symptomatic intracranial bleeding: clinically overt signs of hemorrhage with hemoglobin (Hb) drop of greater than or equal to (>=)5 gram per deciliter (g/dl) (or absolute drop in hematocrit of >=15%) and fatal bleeding (results in death within 7 days); Minor: clinically overt sign of hemorrhage with Hb drop of 3 - <5 g/dl (or drop in hematocrit of 9 - <15%); requiring medical attention: bleeding event that required medical, surgical treatment/laboratory evaluation and did not meet criteria for major/minor bleeding event. Population analyzed included all randomized subjects who had received at least one dose of study drug and had events between randomization and last dose of study drug +2 days or untreated subjects who had events between randomization to 2 days thereafter.
    End point type
    Primary
    End point timeframe
    From start of study treatment until follow-up (up to 390 days)
    End point values
    Rivaroxaban 2.5 mg Twice Daily (BID) Acetylsalicylic acid 100 mg Once Daily (OD)
    Number of subjects analysed
    1519
    1518
    Units: subjects
    80
    74
    Statistical analysis title
    Non CABG-related TIMI
    Comparison groups
    Rivaroxaban 2.5 mg Twice Daily (BID) v Acetylsalicylic acid 100 mg Once Daily (OD)
    Number of subjects included in analysis
    3037
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.584
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.8
         upper limit
    1.5

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 390 days
    Adverse event reporting additional description
    Population analyzed included all randomized subjects who had received at least one dose of study drug and had events between randomization and last dose of study drug +2 days.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Acetylsalicylic acid 100 mg Once Daily (OD)
    Reporting group description
    Subjects received oral dose of 100 mg ASA OD and rivaroxaban placebo BID along with either clopidogrel 75 mg OD or ticagrelor 90 mg BID for a minimum of 180 days, and up to 360 days of treatment.

    Reporting group title
    Rivaroxaban 2.5 mg Twice Daily (BID)
    Reporting group description
    Subjects received oral dose of 2.5 mg rivaroxaban BID and ASA placebo OD along with either clopidogrel 75 mg OD or ticagrelor 90 mg BID for a minimum of 180 days, and up to 360 days of treatment.

    Serious adverse events
    Acetylsalicylic acid 100 mg Once Daily (OD) Rivaroxaban 2.5 mg Twice Daily (BID)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    138 / 1506 (9.16%)
    125 / 1510 (8.28%)
         number of deaths (all causes)
    9
    7
         number of deaths resulting from adverse events
    Vascular disorders
    Aortic Aneurysm
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brachiocephalic Arteriosclerosis
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive Crisis
         subjects affected / exposed
    2 / 1506 (0.13%)
    5 / 1510 (0.33%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral Arterial Occlusive Disease
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral Artery Aneurysm
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral Artery Occlusion
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral Artery Stenosis
         subjects affected / exposed
    1 / 1506 (0.07%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subclavian Artery Stenosis
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular Occlusion
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Inguinal Hernia Repair
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung Neoplasm Surgery
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenectomy
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Brain Neoplasm
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervix Carcinoma Recurrent
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Colon Cancer Recurrent
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric Cancer
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal Carcinoma
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (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
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngeal Cancer
         subjects affected / exposed
    1 / 1506 (0.07%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung Neoplasm Malignant
         subjects affected / exposed
    1 / 1506 (0.07%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic Carcinoma
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Prostate Cancer
         subjects affected / exposed
    1 / 1506 (0.07%)
    2 / 1510 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal Adenocarcinoma
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Renal Neoplasm
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Salivary Gland Cancer Recurrent
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous Cell Carcinoma
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine Cancer
         subjects affected / exposed
    1 / 1506 (0.07%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine Leiomyoma
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular Neoplasm
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest Pain
         subjects affected / exposed
    2 / 1506 (0.13%)
    2 / 1510 (0.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Implant Site Ulcer
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple Organ Dysfunction Syndrome
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Non-Cardiac Chest Pain
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stent-Graft Endoleak
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular Stent Restenosis
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular Stent Stenosis
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Alcohol Withdrawal Syndrome
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    2 / 1506 (0.13%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Panic Attack
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign Prostatic Hyperplasia
         subjects affected / exposed
    1 / 1506 (0.07%)
    1 / 1510 (0.07%)
         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
    Alcohol Poisoning
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary Artery Restenosis
         subjects affected / exposed
    3 / 1506 (0.20%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hand Fracture
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heat Illness
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip Fracture
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus Fracture
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint Dislocation
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament Sprain
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         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
    2 / 1506 (0.13%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar Vertebral Fracture
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius Fracture
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal Fracture
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulna Fracture
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular Access Site Pain
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular Graft Occlusion
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular Pseudoaneurysm
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Cardiac Stress Test Abnormal
         subjects affected / exposed
    2 / 1506 (0.13%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoglobin Decreased
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic Enzyme Increased
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver Function Test Increased
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mediastinoscopy
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight Decreased
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute Left Ventricular Failure
         subjects affected / exposed
    0 / 1506 (0.00%)
    3 / 1510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute Myocardial Infarction
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina Pectoris
         subjects affected / exposed
    2 / 1506 (0.13%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina Unstable
         subjects affected / exposed
    5 / 1506 (0.33%)
    5 / 1510 (0.33%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic Valve Stenosis
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial Fibrillation
         subjects affected / exposed
    7 / 1506 (0.46%)
    3 / 1510 (0.20%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Atrial Flutter
         subjects affected / exposed
    1 / 1506 (0.07%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular Block Second Degree
         subjects affected / exposed
    2 / 1506 (0.13%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac Failure
         subjects affected / exposed
    7 / 1506 (0.46%)
    9 / 1510 (0.60%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac Failure Acute
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac Failure Chronic
         subjects affected / exposed
    0 / 1506 (0.00%)
    3 / 1510 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac Failure Congestive
         subjects affected / exposed
    1 / 1506 (0.07%)
    2 / 1510 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac Ventricular Thrombosis
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiovascular Insufficiency
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary Artery Disease
         subjects affected / exposed
    0 / 1506 (0.00%)
    2 / 1510 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary Artery Stenosis
         subjects affected / exposed
    1 / 1506 (0.07%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracardiac Thrombus
         subjects affected / exposed
    1 / 1506 (0.07%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral Valve Incompetence
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial Fibrosis
         subjects affected / exposed
    2 / 1506 (0.13%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial Ischaemia
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial Rupture
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pericarditis
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleuropericarditis
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postinfarction Angina
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus Arrest
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular Extrasystoles
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute Pulmonary Oedema
         subjects affected / exposed
    2 / 1506 (0.13%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute Respiratory Failure
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Asthma
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic Obstructive Pulmonary Disease
         subjects affected / exposed
    3 / 1506 (0.20%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    4 / 1506 (0.27%)
    4 / 1510 (0.26%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary Embolism
         subjects affected / exposed
    4 / 1506 (0.27%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary Mass
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary Oedema
         subjects affected / exposed
    3 / 1506 (0.20%)
    3 / 1510 (0.20%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory Failure
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Carotid Artery Stenosis
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial Paralysis
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracranial Aneurysm
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    3 / 1506 (0.20%)
    2 / 1510 (0.13%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebral Artery Stenosis
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    2 / 1506 (0.13%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 1506 (0.07%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo Positional
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal Pain
         subjects affected / exposed
    1 / 1506 (0.07%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic Gastritis
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis Ulcerative
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum Intestinal
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erosive Oesophagitis
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 1506 (0.07%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroduodenitis
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal Obstruction
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic Necrosis
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pancreatitis Acute
         subjects affected / exposed
    2 / 1506 (0.13%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis Chronic
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (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
    Acute Kidney Injury
         subjects affected / exposed
    2 / 1506 (0.13%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    2 / 1506 (0.13%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephropathy Toxic
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal Artery Stenosis
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal Colic
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary Retention
         subjects affected / exposed
    0 / 1506 (0.00%)
    2 / 1510 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary Tract Obstruction
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 1506 (0.07%)
    2 / 1510 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis Acute
         subjects affected / exposed
    5 / 1506 (0.33%)
    3 / 1510 (0.20%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 1506 (0.07%)
    3 / 1510 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug-Induced Liver Injury
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (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
    Costochondritis
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral Disc Disorder
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral Disc Protrusion
         subjects affected / exposed
    2 / 1506 (0.13%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligamentitis
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal Discomfort
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (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
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rapidly Progressive Osteoarthritis
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rheumatoid Arthritis
         subjects affected / exposed
    1 / 1506 (0.07%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tenosynovitis
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes Mellitus
         subjects affected / exposed
    2 / 1506 (0.13%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    2 / 1506 (0.13%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 1506 (0.07%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal Infection
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    H1n1 Influenza
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Herpes Zoster
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious Pleural Effusion
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective Exacerbation of Chronic Obstructive Airways Disease
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 1506 (0.00%)
    2 / 1510 (0.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periodontitis
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    5 / 1506 (0.33%)
    7 / 1510 (0.46%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Postoperative Wound Infection
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis Chronic
         subjects affected / exposed
    1 / 1506 (0.07%)
    2 / 1510 (0.13%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory Tract Infection
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal Cord Infection
         subjects affected / exposed
    0 / 1506 (0.00%)
    1 / 1510 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary Tract Infection
         subjects affected / exposed
    1 / 1506 (0.07%)
    0 / 1510 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    Acetylsalicylic acid 100 mg Once Daily (OD) Rivaroxaban 2.5 mg Twice Daily (BID)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    84 / 1506 (5.58%)
    81 / 1510 (5.36%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    22 / 1506 (1.46%)
    23 / 1510 (1.52%)
         occurrences all number
    24
    24
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    14 / 1506 (0.93%)
    16 / 1510 (1.06%)
         occurrences all number
    14
    16
    Dyspnoea
         subjects affected / exposed
    39 / 1506 (2.59%)
    33 / 1510 (2.19%)
         occurrences all number
    39
    34
    General disorders and administration site conditions
    Chest Pain
         subjects affected / exposed
    19 / 1506 (1.26%)
    11 / 1510 (0.73%)
         occurrences all number
    21
    11

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Dec 2014
    The following changes were made in this amendment: modified a number of the inclusion criteria to simplify enrollment of subjects into the study; changes were made to clarify: the definition of the primary endpoint as it related to TIMI clinically significant bleeding events, stratification, the composition and conduct of the committees, the data to be used in the analyses, and the planned interim analysis; changes were made to ensure the evaluation of the cytochrome P450 2C19 genotype in all subjects regardless of P2Y12 inhibitor choice and to modify the timing of parenteral anticoagulants during the index hospitalization to the first dose of the study agent for consistency with the guidelines and previous studies conducted in the acute coronary syndrome (ACS) population.
    21 Apr 2015
    The following changes were made in this amendment: eligibility criteria was revised and it allowed for the inclusion of subjects with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) with positive biomarkers of myocardial necrosis without transient electrocardiogram (ECG) changes if there was a culprit lesion on coronary angiography demonstrating that a recent, active intracoronary atherothrombosis was identified; additionally, subjects with unstable angina without elevated cardiac biomarkers were eligible for enrollment based on ECG changes, a revascularization procedure, or an elevated TIMI risk score; furthermore, the adverse event reporting section was updated to exclude events that were suggestive of and reported as endpoint events from serious adverse event reporting and unblinding procedures.

    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.
    Study population was homogenous with limited participation of non-Caucasian subjects. Randomization was not performed for use of P2Y12 inhibitor; strata comparisons between bleeding and efficacy endpoints are confounded and were not planned.
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