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Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE A)

Sponsor
Sanofi (Industry)
Overall Status
Completed
CT.gov ID
NCT00249873
Collaborator
Bristol-Myers Squibb (Industry)
7,554
Enrollment
30
Locations
2
Arms
69
Duration (Months)
251.8
Patients Per Site
3.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if the combination of clopidogrel 75mg once daily (od) plus aspirin 100mg daily (recommended dose) is better than aspirin alone (100mg daily recommended dose) for preventing vascular events such as stroke and heart attack during approximately three years of follow-up in patients with atrial fibrillation associated with at least one major risk factor of vascular event such as elderly, blood pressure increase, history of stroke or transient ischemic attack or left ventricular dysfunction etc. The study will also accept patients with atrial fibrillation and unwilling to take oral anticoagulant therapy.

Condition or Disease Intervention/Treatment Phase
  • Drug: clopidogrel (SR25990C)
  • Drug: placebo
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
7554 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Prevention
Official Title:
A Parallel Randomized Controlled Evaluation of Clopidogrel Plus Aspirin, With Factorial Evaluation of Irbesartan, for the Prevention of Vascular Events, in Patients With Atrial Fibrillation
Study Start Date :
Jun 1, 2003
Actual Primary Completion Date :
Mar 1, 2009
Actual Study Completion Date :
Mar 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: Clopidogrel + ASA

Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion)

Drug: clopidogrel (SR25990C)
oral administration (tablets)
Other Names:
  • Plavix®

    		•
    Placebo Comparator: Placebo + ASA

    Matching placebo of clopidogrel 75 mg od plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion)

    Drug: placebo
    oral administration (tablets)

    Outcome Measures

    Primary Outcome Measures

    1. First Occurence of Any Component of the Composite of Stroke, Non-Central Nervous System (Non-CNS) Systemic Embolism, Myocardial Infarction or Vascular Death as Per Adjudication [expected median follow-up of approximately 3 years]

      The primary event is the first occurence of any adjudicated component of the following cluster over the duration of follow-up : stroke (nonfatal or fatal) myocardial infarction (nonfatal or fatal) non-CNS systemic embolism vascular death The primary efficacy analysis is performed on the time from randomization to this primary event. Numbers of patients with the composite event over the duration of the follow-up are presented by arm group.

    Secondary Outcome Measures

    1. Occurrence of Stroke [expected median follow-up of approximately 3 years]

      The event is the occurence of stroke (nonfatal or fatal, ischemic, hemorrhagic or of uncertain type) after validation of the Event Adjudication Committee . The analysis is performed on the time from randomization to the occurrence of this event. Numbers of patients with the event over the duration of the follow-up are presented by arm group.

    2. Death From Any Cause (Cardiovascular and Noncardiovascular) [expected median follow-up of approximately 3 years]

      The considered event is death from any cause. The analysis is performed on the time from randomization to this event. Numbers of patients with the event over the duration of the follow-up are presented by arm group.

    3. Adjudicated Major Bleedings [expected median follow-up of approximately 3 years]

      The number of participants with at least one major bleeding, validated by the Event Adjudication Committee are counted over the duration of the follow-up (including after permanent discontinuation of the study drug).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    To be eligible for ACTIVE A patients must have in same time the three following conditions :

    • Evidence of atrial fibrillation either on one current Electrocardiogram (ECG) or two ECGs recorded at two weeks a part during 6 months prior to study enrollment.

    • Evidence of high risk of vascular events : at least one of the following risk criteria must be present :

    • are 75 years greater;

    • on treatment for systemic hypertension;

    • prior stroke, Transient Ischemic Attack (TIA) or non-Central Nervous System (non-CNS) systemic embolus;

    • left ventricular dysfunction with left ventricular ejection fraction (EF) estimated by echocardiogram or angiogram (radionuclide or contrast) to be < 45%;

    • peripheral vascular disease (previous peripheral artery revascularization, limb and foot amputation, or the combination of current intermittent claudication and ankle arm systolic blood pressure ratio < 0.9);

    • age 55 to 74 years and either; f1) diabetes mellitus requiring drug therapy, or f2) documented previous myocardial infarction or documented coronary artery disease.

    • To have either a contraindication to use an oral anticoagulant treatment or they are unwilling to take an oral anticoagulant treatment.

    Exclusion Criteria:
    Patients will be excluded from ACTIVE if any of the following are present :

    • requirement for clopidogrel (such as recent coronary stent procedure)

    • requirement for oral anticoagulant (such as prosthetic mechanical heart valve);

    • prior intolerance to ASA or clopidogrel;

    • documented peptic ulcer disease within the previous 6 months;

    • prior intracerebral hemorrhage;

    • significant thrombocytopenia; (platelet count < 50 x 10(9)/L)

    • psychosocial reason making study participation impractical;

    • geographic reason making study participation impractical;

    • ongoing alcohol abuse;

    • mitral stenosis,

    • pregnant or nursing woman or woman of child bearing potential and not on effective birth control for at least one month prior to start of study or not willing to continue on birth control for duration of study; (severe comorbid condition such that the patient is not expected to survive 6 months;

    • patient currently receiving an investigational pharmacologic agent;

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Sanofi-Aventis Administrative Office Bridgewater New Jersey United States 08807
    2 Sanofi-Aventis Administrative Office Buenos Aires Argentina
    3 Sanofi-Aventis Administrative Office Macquarie Park Australia
    4 Sanofi-Aventis Wien Austria
    5 Sanofi-aventis Administrative Office Diegem Belgium
    6 Sanofi-Aventis Administrative Office Sao Paulo Brazil
    7 Sanofi-Aventis Administrative Office Laval Canada
    8 Sanofi-Aventis Administrative Office Santiago Chile
    9 Sanofi-Aventis Administrative Office Praha Czech Republic
    10 Sanofi-Aventis Administrative Office Horsholm Denmark
    11 Sanofi-Aventis Administrative Office Helsinki Finland
    12 Sanofi-Aventis Administrative Office Paris France
    13 Sanofi-Aventis Administrative Office Berlin Germany
    14 Sanofi-Aventis Administrative Office Athens Greece
    15 Sanofi-Aventis Administrative Office Causeway Bay Hong Kong
    16 Sanofi-Aventis Administrative Office Budapest Hungary
    17 Sanofi-Aventis Administrative Office Milano Italy
    18 Sanofi-Aventis Administrative Office Kuala Lumpur Malaysia
    19 Sanofi-Aventis Administrative Office Mexico Mexico
    20 Sanofi-Aventis Administrative Office Gouda Netherlands
    21 Sanofi-Aventis Administrative Office Lysaker Norway
    22 Sanofi-Aventis Administrative Office Warszawa Poland
    23 Sanofi-Aventis Administrative Office Porto Salvo Portugal
    24 Sanofi-Aventis Administrative Office Singapore Singapore
    25 Sanofi-Aventis Administrative Office Midrand South Africa
    26 Sanofi-Aventis Administrative Office Barcelona Spain
    27 Sanofi-Aventis Administrative Office Bromma Sweden
    28 Sanofi-Aventis Administrative Office Geneva Switzerland
    29 Sanofi-Aventis Administrative Office Taipei Taiwan
    30 Sanofi-Aventis Administrative Office Guildford Surrey United Kingdom

    Sponsors and Collaborators

    • Sanofi
    • Bristol-Myers Squibb

    Investigators

    • Study Chair: Philippe YUSUF, Prof., Hamilton Health Sciences Corporation

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sanofi
    ClinicalTrials.gov Identifier:
    NCT00249873
    Other Study ID Numbers:
    • EFC4912 A
    First Posted:
    Nov 7, 2005
    Last Update Posted:
    Jun 15, 2015
    Last Verified:
    May 1, 2015
    Keywords provided by Sanofi
    Atrial fibrillation
    Anticoagulant therapy
    Thromboembolic prevention
    Additional relevant MeSH terms:
    Atrial Fibrillation
    Clopidogrel

    Study Results

    Participant Flow

    Recruitment Details Patients were enrolled from June 2003 until May 2006. The study was conducted at 580 centers in 33 countries. The planned final follow-up visit date ensuring a median follow-up of three years was November 2008. The follow-up of the study was actually completed on March 2009 corresponding to an actual median follow-up of 3.5 years.
    Pre-assignment Detail
    Arm/Group Title Clopidogrel + ASA Placebo + ASA
    Arm/Group Description Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion) Matching placebo of clopidogrel 75 mg od plus ASA 75 to 100 mg od recommended (dose at the investigators' discretion)
    Period Title: Overall Study
    STARTED 3772 3782
    COMPLETED 2442 2528
    NOT COMPLETED 1330 1254

    Baseline Characteristics

    Arm/Group Title Clopidogrel + ASA Placebo + ASA Total
    Arm/Group Description Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion) Matching placebo of clopidogrel 75 mg od plus ASA 75 to 100 mg od recommended (dose at the investigators' discretion) Total of all reporting groups
    Overall Participants 3772 3782 7554
    Age, Customized (participants) [Number]
    18 to <65 years
    931
    24.7%
    935
    24.7%
    1866
    24.7%
    65 to <75 years
    1291
    34.2%
    1258
    33.3%
    2549
    33.7%
    >= 75 years
    1550
    41.1%
    1589
    42%
    3139
    41.6%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    70.9
    (10.2)
    71.1
    (10.2)
    71.0
    (10.2)
    Sex: Female, Male (Count of Participants)
    Female
    1560
    41.4%
    1597
    42.2%
    3157
    41.8%
    Male
    2212
    58.6%
    2185
    57.8%
    4397
    58.2%
    CHADS2 Score (participants) [Number]
    0
    105
    2.8%
    101
    2.7%
    206
    2.7%
    1
    1360
    36.1%
    1338
    35.4%
    2698
    35.7%
    2
    1263
    33.5%
    1315
    34.8%
    2578
    34.1%
    >2
    1040
    27.6%
    1028
    27.2%
    2068
    27.4%
    Missing
    4
    0.1%
    0
    0%
    4
    0.1%
    Sitting Systolic Blood Pressure (participants) [Number]
    <120 mmHg
    603
    16%
    620
    16.4%
    1223
    16.2%
    >=120 mmHg
    3166
    83.9%
    3159
    83.5%
    6325
    83.7%
    Missing
    3
    0.1%
    3
    0.1%
    6
    0.1%
    Body Mass Index (BMI) (kg/m²) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m²]
    28.370
    (5.575)
    28.459
    (6.022)
    28.415
    (5.803)

    Outcome Measures

    1. Primary Outcome
    Title First Occurence of Any Component of the Composite of Stroke, Non-Central Nervous System (Non-CNS) Systemic Embolism, Myocardial Infarction or Vascular Death as Per Adjudication
    Description The primary event is the first occurence of any adjudicated component of the following cluster over the duration of follow-up : stroke (nonfatal or fatal) myocardial infarction (nonfatal or fatal) non-CNS systemic embolism vascular death The primary efficacy analysis is performed on the time from randomization to this primary event. Numbers of patients with the composite event over the duration of the follow-up are presented by arm group.
    Time Frame expected median follow-up of approximately 3 years

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) population was used for all analyses. This consisted of all randomized patients irrespective of whether or not the patient actually received study drug or the patient's compliance with the study protocol. All patients were included in the treatment group to which they were originally allocated.
    Arm/Group Title Clopidogrel + ASA Placebo + ASA
    Arm/Group Description Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion) Matching placebo of clopidogrel 75 mg od plus ASA 75 to 100 mg od recommended (dose at the investigators' discretion)
    Measure Participants 3772 3782
    All components
    832
    22.1%
    924
    24.4%
    - Myocardial Infarction (fatal or not)
    84
    2.2%
    105
    2.8%
    - Stroke (fatal or not)
    285
    7.6%
    391
    10.3%
    - Non-CNS systemic embolism
    50
    1.3%
    48
    1.3%
    - Vascular death
    413
    10.9%
    380
    10%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Clopidogrel + ASA, Placebo + ASA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0133
    Comments Cumulative incidence functions in each treatment group were calculated using non-parametric Kaplan-Meier estimates. Median time-to-event was not reached in any group. The primary comparison was performed at the 5% level using a 2-sided Log rank test.
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.89
    Confidence Interval () 95%
    0.81 to 0.98
    Parameter Dispersion Type:
    Value:
    Estimation Comments The hazard ratio was estimated by a Cox's proportional hazard model with treatment arm factor. It represents the relative hazard of any component of the primary event for the clopidogrel group compared with the Placebo group.
    2. Secondary Outcome
    Title Occurrence of Stroke
    Description The event is the occurence of stroke (nonfatal or fatal, ischemic, hemorrhagic or of uncertain type) after validation of the Event Adjudication Committee . The analysis is performed on the time from randomization to the occurrence of this event. Numbers of patients with the event over the duration of the follow-up are presented by arm group.
    Time Frame expected median follow-up of approximately 3 years

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) population was used for this analysis.
    Arm/Group Title Clopidogrel + ASA Placebo + ASA
    Arm/Group Description Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion) Matching placebo of clopidogrel 75 mg od plus ASA 75 to 100 mg od recommended (dose at the investigators' discretion)
    Measure Participants 3772 3782
    Number [participants]
    296
    7.8%
    408
    10.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Clopidogrel + ASA, Placebo + ASA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Cumulative incidence functions in each treatment group were calculated using non-parametric Kaplan-Meier estimates. Median time-to-event was not reached in any group. The primary comparison was performed at the 5% level using a 2-sided Log rank test.
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.72
    Confidence Interval () 95%
    0.62 to 0.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments The hazard ratio was estimated by a Cox's proportional hazard model with treatment arm factor. It represents the relative hazard of stroke for the clopidogrel group compared with the Placebo group.
    3. Secondary Outcome
    Title Death From Any Cause (Cardiovascular and Noncardiovascular)
    Description The considered event is death from any cause. The analysis is performed on the time from randomization to this event. Numbers of patients with the event over the duration of the follow-up are presented by arm group.
    Time Frame expected median follow-up of approximately 3 years

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) population was used for the analysis.
    Arm/Group Title Clopidogrel + ASA Placebo + ASA
    Arm/Group Description Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion) Matching placebo of clopidogrel 75 mg od plus ASA 75 to 100 mg od recommended (dose at the investigators' discretion)
    Measure Participants 3772 3782
    Number [participants]
    825
    21.9%
    841
    22.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Clopidogrel + ASA, Placebo + ASA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.696
    Comments Cumulative incidence functions in each treatment group were calculated using non-parametric Kaplan-Meier estimates. Median time-to-event was not reached in any group. The primary comparison was performed at the 5% level using a 2-sided Log rank test.
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.98
    Confidence Interval () 95%
    0.89 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments The hazard ratio was estimated by a Cox's proportional hazard model with treatment arm factor. It represents the relative hazard of death from any cause for the clopidogrel group compared with the Placebo group.
    4. Secondary Outcome
    Title Adjudicated Major Bleedings
    Description The number of participants with at least one major bleeding, validated by the Event Adjudication Committee are counted over the duration of the follow-up (including after permanent discontinuation of the study drug).
    Time Frame expected median follow-up of approximately 3 years

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) population was used for the analysis.
    Arm/Group Title Clopidogrel + ASA Placebo + ASA
    Arm/Group Description Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion) Matching placebo of clopidogrel 75 mg od plus ASA 75 to 100 mg od recommended (dose at the investigators' discretion)
    Measure Participants 3772 3782
    Number [participants]
    251
    6.7%
    162
    4.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Clopidogrel + ASA, Placebo + ASA
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Chi-squared
    Comments

    Adverse Events

    Time Frame From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months.
    Adverse Event Reporting Description The intent to treat population was also used for safety analyses.
    Arm/Group Title Clopidogrel + ASA Placebo + ASA
    Arm/Group Description Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion) Matching placebo of clopidogrel 75 mg od plus ASA 75 to 100 mg od recommended (dose at the investigators' discretion)
    All Cause Mortality
    Clopidogrel + ASA Placebo + ASA
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Clopidogrel + ASA Placebo + ASA
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1154/3772 (30.6%) 1069/3782 (28.3%)
    Blood and lymphatic system disorders
    Anaemia 18/3772 (0.5%) 19/3782 (0.5%)
    Anaemia megaloblastic 0/3772 (0%) 1/3782 (0%)
    Anaemia of chronic disease 1/3772 (0%) 1/3782 (0%)
    Anaemia of malignant disease 1/3772 (0%) 1/3782 (0%)
    Haemorrhagic anaemia 0/3772 (0%) 1/3782 (0%)
    Haemorrhagic disorder 0/3772 (0%) 1/3782 (0%)
    Hypochromic anaemia 1/3772 (0%) 0/3782 (0%)
    Iron deficiency anaemia 4/3772 (0.1%) 2/3782 (0.1%)
    Nephrogenic anaemia 1/3772 (0%) 1/3782 (0%)
    Pancytopenia 0/3772 (0%) 1/3782 (0%)
    Thrombocytopenia 6/3772 (0.2%) 2/3782 (0.1%)
    Cardiac disorders
    Angina pectoris 1/3772 (0%) 0/3782 (0%)
    Atrial fibrillation 0/3772 (0%) 1/3782 (0%)
    Atrioventricular block complete 1/3772 (0%) 0/3782 (0%)
    Bradycardia 0/3772 (0%) 1/3782 (0%)
    Cardiac amyloidosis 0/3772 (0%) 1/3782 (0%)
    Cardiopulmonary failure 0/3772 (0%) 1/3782 (0%)
    Congestive cardiomyopathy 0/3772 (0%) 1/3782 (0%)
    Intracardiac thrombus 1/3772 (0%) 1/3782 (0%)
    Pericardial haemorrhage 1/3772 (0%) 0/3782 (0%)
    Pericarditis 1/3772 (0%) 0/3782 (0%)
    Sinoatrial block 0/3772 (0%) 1/3782 (0%)
    Tricuspid valve disease 0/3772 (0%) 1/3782 (0%)
    Congenital, familial and genetic disorders
    Adenomatous polyposis coli 0/3772 (0%) 1/3782 (0%)
    Dermoid cyst 0/3772 (0%) 1/3782 (0%)
    Gastrointestinal angiodysplasia 1/3772 (0%) 0/3782 (0%)
    Gastrointestinal angiodysplasia haemorrhagic 2/3772 (0.1%) 0/3782 (0%)
    Hydrocele 2/3772 (0.1%) 1/3782 (0%)
    Muscular dystrophy 1/3772 (0%) 0/3782 (0%)
    Phimosis 0/3772 (0%) 4/3782 (0.1%)
    Ear and labyrinth disorders
    Deafness neurosensory 1/3772 (0%) 0/3782 (0%)
    Hearing impaired 1/3772 (0%) 2/3782 (0.1%)
    Sudden hearing loss 0/3772 (0%) 1/3782 (0%)
    Vertigo 2/3772 (0.1%) 7/3782 (0.2%)
    Vertigo positional 2/3772 (0.1%) 2/3782 (0.1%)
    Vestibular disorder 1/3772 (0%) 0/3782 (0%)
    Endocrine disorders
    Autoimmune thyroiditis 0/3772 (0%) 1/3782 (0%)
    Diabetes insipidus 0/3772 (0%) 1/3782 (0%)
    Ectopic hyperthyroidism 0/3772 (0%) 1/3782 (0%)
    Goitre 3/3772 (0.1%) 1/3782 (0%)
    Hyperparathyroidism 1/3772 (0%) 0/3782 (0%)
    Hyperparathyroidism secondary 0/3772 (0%) 1/3782 (0%)
    Hyperthyroidism 2/3772 (0.1%) 9/3782 (0.2%)
    Hypothyroidism 0/3772 (0%) 1/3782 (0%)
    Thyroiditis 0/3772 (0%) 1/3782 (0%)
    Toxic nodular goitre 0/3772 (0%) 2/3782 (0.1%)
    Eye disorders
    Angle closure glaucoma 1/3772 (0%) 0/3782 (0%)
    Cataract 20/3772 (0.5%) 18/3782 (0.5%)
    Corneal degeneration 1/3772 (0%) 0/3782 (0%)
    Diplopia 1/3772 (0%) 0/3782 (0%)
    Eye haemorrhage 0/3772 (0%) 2/3782 (0.1%)
    Eyelid oedema 0/3772 (0%) 1/3782 (0%)
    Glaucoma 2/3772 (0.1%) 1/3782 (0%)
    Maculopathy 1/3772 (0%) 0/3782 (0%)
    Pupils unequal 1/3772 (0%) 0/3782 (0%)
    Retinal artery occlusion 0/3772 (0%) 2/3782 (0.1%)
    Retinal degeneration 0/3772 (0%) 1/3782 (0%)
    Retinal detachment 1/3772 (0%) 3/3782 (0.1%)
    Retinal haemorrhage 1/3772 (0%) 1/3782 (0%)
    Retinal vein thrombosis 1/3772 (0%) 0/3782 (0%)
    Visual impairment 0/3772 (0%) 1/3782 (0%)
    Gastrointestinal disorders
    Abdominal hernia 1/3772 (0%) 4/3782 (0.1%)
    Abdominal pain 4/3772 (0.1%) 8/3782 (0.2%)
    Abdominal pain upper 1/3772 (0%) 4/3782 (0.1%)
    Abdominal strangulated hernia 3/3772 (0.1%) 0/3782 (0%)
    Acute abdomen 2/3772 (0.1%) 1/3782 (0%)
    Anal fissure 2/3772 (0.1%) 0/3782 (0%)
    Anal haemorrhage 0/3772 (0%) 1/3782 (0%)
    Appendicitis perforated 1/3772 (0%) 0/3782 (0%)
    Barrett's oesophagus 0/3772 (0%) 1/3782 (0%)
    Coeliac disease 0/3772 (0%) 1/3782 (0%)
    Colitis 0/3772 (0%) 3/3782 (0.1%)
    Colitis ischaemic 1/3772 (0%) 0/3782 (0%)
    Colitis ulcerative 2/3772 (0.1%) 1/3782 (0%)
    Colonic polyp 4/3772 (0.1%) 6/3782 (0.2%)
    Colonic stenosis 1/3772 (0%) 0/3782 (0%)
    Constipation 4/3772 (0.1%) 5/3782 (0.1%)
    Diarrhoea 11/3772 (0.3%) 10/3782 (0.3%)
    Diarrhoea haemorrhagic 0/3772 (0%) 1/3782 (0%)
    Diverticular perforation 0/3772 (0%) 1/3782 (0%)
    Diverticulitis intestinal haemorrhagic 3/3772 (0.1%) 1/3782 (0%)
    Diverticulum 4/3772 (0.1%) 2/3782 (0.1%)
    Diverticulum intestinal 2/3772 (0.1%) 3/3782 (0.1%)
    Diverticulum intestinal haemorrhagic 5/3772 (0.1%) 0/3782 (0%)
    Duodenal ulcer 1/3772 (0%) 3/3782 (0.1%)
    Duodenal ulcer haemorrhage 6/3772 (0.2%) 7/3782 (0.2%)
    Duodenal ulcer perforation 1/3772 (0%) 0/3782 (0%)
    Duodenitis 1/3772 (0%) 1/3782 (0%)
    Dyspepsia 3/3772 (0.1%) 3/3782 (0.1%)
    Dysphagia 1/3772 (0%) 2/3782 (0.1%)
    Enterocolitis 2/3772 (0.1%) 1/3782 (0%)
    Enterocolitis haemorrhagic 3/3772 (0.1%) 1/3782 (0%)
    Faecaloma 0/3772 (0%) 1/3782 (0%)
    Femoral hernia 1/3772 (0%) 0/3782 (0%)
    Femoral hernia, obstructive 0/3772 (0%) 1/3782 (0%)
    Food poisoning 1/3772 (0%) 0/3782 (0%)
    Gallstone ileus 0/3772 (0%) 1/3782 (0%)
    Gastric antral vascular ectasia 1/3772 (0%) 0/3782 (0%)
    Gastric haemorrhage 4/3772 (0.1%) 1/3782 (0%)
    Gastric mucosal lesion 1/3772 (0%) 1/3782 (0%)
    Gastric polyps 1/3772 (0%) 0/3782 (0%)
    Gastric ulcer 8/3772 (0.2%) 3/3782 (0.1%)
    Gastric ulcer haemorrhage 21/3772 (0.6%) 6/3782 (0.2%)
    Gastritis 8/3772 (0.2%) 7/3782 (0.2%)
    Gastritis erosive 2/3772 (0.1%) 1/3782 (0%)
    Gastritis haemorrhagic 9/3772 (0.2%) 3/3782 (0.1%)
    Gastroduodenal ulcer 0/3772 (0%) 1/3782 (0%)
    Gastroduodenitis 2/3772 (0.1%) 0/3782 (0%)
    Gastrointestinal haemorrhage 26/3772 (0.7%) 9/3782 (0.2%)
    Gastrointestinal necrosis 1/3772 (0%) 0/3782 (0%)
    Gastrointestinal ulcer haemorrhage 2/3772 (0.1%) 1/3782 (0%)
    Gastrooesophageal reflux disease 5/3772 (0.1%) 1/3782 (0%)
    Gastrooesophagitis 1/3772 (0%) 1/3782 (0%)
    Haematochezia 0/3772 (0%) 1/3782 (0%)
    Haemorrhoidal haemorrhage 0/3772 (0%) 2/3782 (0.1%)
    Haemorrhoids 3/3772 (0.1%) 3/3782 (0.1%)
    Hiatus hernia 1/3772 (0%) 1/3782 (0%)
    Ileus 6/3772 (0.2%) 4/3782 (0.1%)
    Inguinal hernia 18/3772 (0.5%) 17/3782 (0.4%)
    Inguinal hernia, obstructive 1/3772 (0%) 1/3782 (0%)
    Intestinal dilatation 0/3772 (0%) 1/3782 (0%)
    Intestinal functional disorder 1/3772 (0%) 0/3782 (0%)
    Intestinal haemorrhage 3/3772 (0.1%) 1/3782 (0%)
    Intestinal infarction 1/3772 (0%) 0/3782 (0%)
    Intestinal ischaemia 2/3772 (0.1%) 1/3782 (0%)
    Intestinal obstruction 7/3772 (0.2%) 5/3782 (0.1%)
    Intestinal perforation 4/3772 (0.1%) 0/3782 (0%)
    Intestinal polyp 1/3772 (0%) 0/3782 (0%)
    Intestinal strangulation 1/3772 (0%) 0/3782 (0%)
    Intra-abdominal haematoma 0/3772 (0%) 1/3782 (0%)
    Intra-abdominal haemorrhage 1/3772 (0%) 1/3782 (0%)
    Irritable bowel syndrome 0/3772 (0%) 1/3782 (0%)
    Large intestinal haemorrhage 1/3772 (0%) 0/3782 (0%)
    Large intestine perforation 0/3772 (0%) 1/3782 (0%)
    Lower gastrointestinal haemorrhage 13/3772 (0.3%) 3/3782 (0.1%)
    Mallory-weiss syndrome 1/3772 (0%) 0/3782 (0%)
    Mechanical ileus 2/3772 (0.1%) 0/3782 (0%)
    Melaena 1/3772 (0%) 1/3782 (0%)
    Mesenteric occlusion 0/3772 (0%) 1/3782 (0%)
    Nausea 0/3772 (0%) 3/3782 (0.1%)
    Oesophageal perforation 0/3772 (0%) 1/3782 (0%)
    Oesophageal ulcer 1/3772 (0%) 1/3782 (0%)
    Oesophageal ulcer haemorrhage 0/3772 (0%) 1/3782 (0%)
    Oesophageal varices haemorrhage 0/3772 (0%) 1/3782 (0%)
    Oesophagitis 1/3772 (0%) 1/3782 (0%)
    Oesophagitis haemorrhagic 1/3772 (0%) 0/3782 (0%)
    Pancreatitis 4/3772 (0.1%) 8/3782 (0.2%)
    Pancreatitis acute 1/3772 (0%) 4/3782 (0.1%)
    Pancreatitis chronic 2/3772 (0.1%) 1/3782 (0%)
    Peptic ulcer 2/3772 (0.1%) 3/3782 (0.1%)
    Peptic ulcer haemorrhage 5/3772 (0.1%) 1/3782 (0%)
    Periodontitis 0/3772 (0%) 1/3782 (0%)
    Peritoneal adhesions 1/3772 (0%) 0/3782 (0%)
    Peritonitis 4/3772 (0.1%) 3/3782 (0.1%)
    Rectal haemorrhage 10/3772 (0.3%) 1/3782 (0%)
    Rectal polyp 2/3772 (0.1%) 1/3782 (0%)
    Rectal prolapse 1/3772 (0%) 0/3782 (0%)
    Reflux oesophagitis 0/3772 (0%) 2/3782 (0.1%)
    Retroperitoneal haematoma 1/3772 (0%) 0/3782 (0%)
    Retroperitoneal haemorrhage 1/3772 (0%) 2/3782 (0.1%)
    Salivary gland calculus 1/3772 (0%) 0/3782 (0%)
    Small intestinal obstruction 4/3772 (0.1%) 1/3782 (0%)
    Stomatitis 0/3772 (0%) 1/3782 (0%)
    Subileus 6/3772 (0.2%) 1/3782 (0%)
    Tooth disorder 1/3772 (0%) 0/3782 (0%)
    Umbilical hernia 1/3772 (0%) 1/3782 (0%)
    Umbilical hernia, obstructive 1/3772 (0%) 0/3782 (0%)
    Upper gastrointestinal haemorrhage 28/3772 (0.7%) 7/3782 (0.2%)
    Volvulus 0/3772 (0%) 1/3782 (0%)
    Vomiting 6/3772 (0.2%) 4/3782 (0.1%)
    General disorders
    Asthenia 2/3772 (0.1%) 3/3782 (0.1%)
    Chest pain 7/3772 (0.2%) 8/3782 (0.2%)
    Cyst 1/3772 (0%) 0/3782 (0%)
    Death 1/3772 (0%) 2/3782 (0.1%)
    Dysplasia 0/3772 (0%) 1/3782 (0%)
    Fatigue 1/3772 (0%) 2/3782 (0.1%)
    Gait disturbance 2/3772 (0.1%) 0/3782 (0%)
    General physical health deterioration 7/3772 (0.2%) 4/3782 (0.1%)
    Generalised oedema 2/3772 (0.1%) 0/3782 (0%)
    Hernia 1/3772 (0%) 0/3782 (0%)
    Malaise 0/3772 (0%) 2/3782 (0.1%)
    Multi-organ failure 8/3772 (0.2%) 8/3782 (0.2%)
    Non-cardiac chest pain 3/3772 (0.1%) 8/3782 (0.2%)
    Oedema peripheral 2/3772 (0.1%) 0/3782 (0%)
    Pelvic mass 1/3772 (0%) 0/3782 (0%)
    Perforated ulcer 0/3772 (0%) 1/3782 (0%)
    Performance status decreased 1/3772 (0%) 0/3782 (0%)
    Puncture site haemorrhage 1/3772 (0%) 1/3782 (0%)
    Pyrexia 4/3772 (0.1%) 4/3782 (0.1%)
    Submandibular mass 1/3772 (0%) 0/3782 (0%)
    Swelling 1/3772 (0%) 0/3782 (0%)
    Hepatobiliary disorders
    Alcoholic liver disease 0/3772 (0%) 1/3782 (0%)
    Bile duct obstruction 0/3772 (0%) 1/3782 (0%)
    Bile duct stenosis 0/3772 (0%) 1/3782 (0%)
    Bile duct stone 2/3772 (0.1%) 2/3782 (0.1%)
    Biliary cirrhosis primary 0/3772 (0%) 1/3782 (0%)
    Biliary colic 1/3772 (0%) 2/3782 (0.1%)
    Cholangitis 1/3772 (0%) 2/3782 (0.1%)
    Cholangitis acute 1/3772 (0%) 0/3782 (0%)
    Cholecystitis 16/3772 (0.4%) 12/3782 (0.3%)
    Cholecystitis acute 5/3772 (0.1%) 9/3782 (0.2%)
    Cholecystitis chronic 3/3772 (0.1%) 0/3782 (0%)
    Cholelithiasis 16/3772 (0.4%) 18/3782 (0.5%)
    Cholestasis 0/3772 (0%) 1/3782 (0%)
    Cirrhosis alcoholic 2/3772 (0.1%) 0/3782 (0%)
    Hepatic cirrhosis 2/3772 (0.1%) 2/3782 (0.1%)
    Hepatic congestion 0/3772 (0%) 3/3782 (0.1%)
    Hepatic cyst 0/3772 (0%) 1/3782 (0%)
    Hepatic failure 1/3772 (0%) 0/3782 (0%)
    Hepatic function abnormal 1/3772 (0%) 0/3782 (0%)
    Hepatic mass 1/3772 (0%) 0/3782 (0%)
    Hepatitis 1/3772 (0%) 0/3782 (0%)
    Hepatitis acute 0/3772 (0%) 1/3782 (0%)
    Hepatitis alcoholic 1/3772 (0%) 0/3782 (0%)
    Hepatitis toxic 1/3772 (0%) 0/3782 (0%)
    Hepatocellular injury 1/3772 (0%) 0/3782 (0%)
    Hyperbilirubinaemia 0/3772 (0%) 1/3782 (0%)
    Jaundice 2/3772 (0.1%) 2/3782 (0.1%)
    Jaundice cholestatic 0/3772 (0%) 2/3782 (0.1%)
    Post cholecystectomy syndrome 1/3772 (0%) 0/3782 (0%)
    Immune system disorders
    Drug hypersensitivity 1/3772 (0%) 0/3782 (0%)
    Hypersensitivity 2/3772 (0.1%) 2/3782 (0.1%)
    Infections and infestations
    Abdominal sepsis 0/3772 (0%) 1/3782 (0%)
    Abscess 2/3772 (0.1%) 0/3782 (0%)
    Abscess neck 1/3772 (0%) 0/3782 (0%)
    Acarodermatitis 1/3772 (0%) 0/3782 (0%)
    American trypanosomiasis 0/3772 (0%) 1/3782 (0%)
    Anogenital warts 1/3772 (0%) 0/3782 (0%)
    Appendiceal abscess 1/3772 (0%) 1/3782 (0%)
    Appendicitis 7/3772 (0.2%) 3/3782 (0.1%)
    Arthritis bacterial 0/3772 (0%) 1/3782 (0%)
    Arthritis infective 0/3772 (0%) 1/3782 (0%)
    Bacteraemia 3/3772 (0.1%) 3/3782 (0.1%)
    Bacterial infection 1/3772 (0%) 0/3782 (0%)
    Biliary tract infection 0/3772 (0%) 1/3782 (0%)
    Breast abscess 1/3772 (0%) 0/3782 (0%)
    Bronchiectasis 1/3772 (0%) 2/3782 (0.1%)
    Bronchitis 20/3772 (0.5%) 13/3782 (0.3%)
    Bronchitis viral 0/3772 (0%) 1/3782 (0%)
    Bronchopneumonia 10/3772 (0.3%) 15/3782 (0.4%)
    Cellulitis 9/3772 (0.2%) 7/3782 (0.2%)
    Central line infection 1/3772 (0%) 0/3782 (0%)
    Chronic sinusitis 0/3772 (0%) 2/3782 (0.1%)
    Clostridial infection 0/3772 (0%) 2/3782 (0.1%)
    Clostridium difficile colitis 1/3772 (0%) 1/3782 (0%)
    Corneal abscess 1/3772 (0%) 0/3782 (0%)
    Cryptosporidiosis infection 1/3772 (0%) 0/3782 (0%)
    Cystitis 2/3772 (0.1%) 0/3782 (0%)
    Dengue fever 0/3772 (0%) 1/3782 (0%)
    Dermo-hypodermitis 0/3772 (0%) 1/3782 (0%)
    Device related infection 1/3772 (0%) 2/3782 (0.1%)
    Diverticulitis 11/3772 (0.3%) 7/3782 (0.2%)
    Emphysematous cholecystitis 1/3772 (0%) 0/3782 (0%)
    Empyema 1/3772 (0%) 0/3782 (0%)
    Endocarditis 0/3772 (0%) 1/3782 (0%)
    Endocarditis bacterial 0/3772 (0%) 1/3782 (0%)
    Enterocolitis infectious 0/3772 (0%) 1/3782 (0%)
    Erysipelas 5/3772 (0.1%) 10/3782 (0.3%)
    Escherichia infection 0/3772 (0%) 1/3782 (0%)
    Gallbladder empyema 1/3772 (0%) 2/3782 (0.1%)
    Gangrene 0/3772 (0%) 2/3782 (0.1%)
    Gastroenteritis 13/3772 (0.3%) 10/3782 (0.3%)
    Gastroenteritis norovirus 0/3772 (0%) 1/3782 (0%)
    Gastroenteritis salmonella 0/3772 (0%) 1/3782 (0%)
    Gastroenteritis viral 1/3772 (0%) 0/3782 (0%)
    Gastrointestinal infection 1/3772 (0%) 0/3782 (0%)
    Groin abscess 1/3772 (0%) 0/3782 (0%)
    Haematoma infection 1/3772 (0%) 2/3782 (0.1%)
    Hepatitis e 1/3772 (0%) 0/3782 (0%)
    Herpes zoster 2/3772 (0.1%) 2/3782 (0.1%)
    Herpes zoster ophthalmic 1/3772 (0%) 0/3782 (0%)
    Implant site infection 1/3772 (0%) 0/3782 (0%)
    Infected skin ulcer 1/3772 (0%) 1/3782 (0%)
    Infection 2/3772 (0.1%) 0/3782 (0%)
    Infective exacerbation of chronic obstructive airways disease 0/3772 (0%) 1/3782 (0%)
    Influenza 3/3772 (0.1%) 4/3782 (0.1%)
    Intervertebral discitis 1/3772 (0%) 0/3782 (0%)
    Keratitis fungal 1/3772 (0%) 0/3782 (0%)
    Labyrinthitis 0/3772 (0%) 1/3782 (0%)
    Lobar pneumonia 7/3772 (0.2%) 10/3782 (0.3%)
    Localised infection 2/3772 (0.1%) 1/3782 (0%)
    Lower respiratory tract infection 5/3772 (0.1%) 7/3782 (0.2%)
    Lower respiratory tract infection viral 0/3772 (0%) 1/3782 (0%)
    Lung infection 5/3772 (0.1%) 4/3782 (0.1%)
    Meningitis 1/3772 (0%) 1/3782 (0%)
    Nasopharyngitis 1/3772 (0%) 0/3782 (0%)
    Necrotising fasciitis 0/3772 (0%) 2/3782 (0.1%)
    Orchitis 1/3772 (0%) 0/3782 (0%)
    Osteomyelitis 0/3772 (0%) 3/3782 (0.1%)
    Otitis externa 0/3772 (0%) 1/3782 (0%)
    Otitis media 1/3772 (0%) 0/3782 (0%)
    Parotitis 0/3772 (0%) 2/3782 (0.1%)
    Perirectal abscess 1/3772 (0%) 0/3782 (0%)
    Peritoneal infection 1/3772 (0%) 1/3782 (0%)
    Pharyngitis 1/3772 (0%) 1/3782 (0%)
    Pilonidal cyst 0/3772 (0%) 1/3782 (0%)
    Pneumococcal infection 1/3772 (0%) 0/3782 (0%)
    Pneumonia 139/3772 (3.7%) 128/3782 (3.4%)
    Pneumonia klebsiella 2/3772 (0.1%) 1/3782 (0%)
    Pneumonia primary atypical 2/3772 (0.1%) 0/3782 (0%)
    Pneumonia staphylococcal 0/3772 (0%) 2/3782 (0.1%)
    Pneumonia streptococcal 0/3772 (0%) 1/3782 (0%)
    Portal pyaemia 1/3772 (0%) 0/3782 (0%)
    Post procedural infection 2/3772 (0.1%) 2/3782 (0.1%)
    Post procedural sepsis 0/3772 (0%) 1/3782 (0%)
    Postoperative wound infection 3/3772 (0.1%) 2/3782 (0.1%)
    Pseudomonas infection 1/3772 (0%) 0/3782 (0%)
    Pulmonary sepsis 1/3772 (0%) 0/3782 (0%)
    Pulmonary tuberculosis 1/3772 (0%) 2/3782 (0.1%)
    Pyelonephritis 5/3772 (0.1%) 10/3782 (0.3%)
    Pyelonephritis acute 1/3772 (0%) 2/3782 (0.1%)
    Renal abscess 0/3772 (0%) 2/3782 (0.1%)
    Respiratory tract infection 8/3772 (0.2%) 6/3782 (0.2%)
    Sepsis 27/3772 (0.7%) 19/3782 (0.5%)
    Sepsis syndrome 0/3772 (0%) 1/3782 (0%)
    Septic shock 6/3772 (0.2%) 10/3782 (0.3%)
    Sinusitis 1/3772 (0%) 2/3782 (0.1%)
    Skin bacterial infection 1/3772 (0%) 0/3782 (0%)
    Staphylococcal infection 0/3772 (0%) 1/3782 (0%)
    Staphylococcal sepsis 1/3772 (0%) 0/3782 (0%)
    Staphylococcal toxaemia 0/3772 (0%) 1/3782 (0%)
    Streptococcal sepsis 1/3772 (0%) 0/3782 (0%)
    Subcutaneous abscess 1/3772 (0%) 1/3782 (0%)
    Tetanus 1/3772 (0%) 0/3782 (0%)
    Thrombophlebitis septic 0/3772 (0%) 1/3782 (0%)
    Tooth abscess 1/3772 (0%) 1/3782 (0%)
    Toxic shock syndrome 0/3772 (0%) 1/3782 (0%)
    Tracheobronchitis 0/3772 (0%) 1/3782 (0%)
    Tuberculosis 0/3772 (0%) 2/3782 (0.1%)
    Upper respiratory tract infection 5/3772 (0.1%) 6/3782 (0.2%)
    Urethritis 0/3772 (0%) 1/3782 (0%)
    Urinary tract infection 23/3772 (0.6%) 28/3782 (0.7%)
    Urosepsis 7/3772 (0.2%) 7/3782 (0.2%)
    Viral infection 3/3772 (0.1%) 3/3782 (0.1%)
    Viral pericarditis 0/3772 (0%) 1/3782 (0%)
    Vulval abscess 0/3772 (0%) 1/3782 (0%)
    Wound infection 4/3772 (0.1%) 4/3782 (0.1%)
    Wound infection staphylococcal 1/3772 (0%) 0/3782 (0%)
    Injury, poisoning and procedural complications
    Abdominal wound dehiscence 0/3772 (0%) 1/3782 (0%)
    Accidental overdose 1/3772 (0%) 0/3782 (0%)
    Alcohol poisoning 1/3772 (0%) 0/3782 (0%)
    Anaemia postoperative 1/3772 (0%) 0/3782 (0%)
    Anastomotic leak 0/3772 (0%) 1/3782 (0%)
    Anastomotic stenosis 0/3772 (0%) 1/3782 (0%)
    Anastomotic ulcer haemorrhage 1/3772 (0%) 0/3782 (0%)
    Ankle fracture 3/3772 (0.1%) 4/3782 (0.1%)
    Asbestosis 1/3772 (0%) 0/3782 (0%)
    Brain contusion 1/3772 (0%) 0/3782 (0%)
    Concussion 1/3772 (0%) 4/3782 (0.1%)
    Contusion 6/3772 (0.2%) 4/3782 (0.1%)
    Dislocation of joint prosthesis 1/3772 (0%) 0/3782 (0%)
    Drug toxicity 1/3772 (0%) 7/3782 (0.2%)
    Ear injury 0/3772 (0%) 1/3782 (0%)
    Epiphyseal fracture 0/3772 (0%) 1/3782 (0%)
    Extradural haematoma 1/3772 (0%) 1/3782 (0%)
    Facial bones fracture 2/3772 (0.1%) 3/3782 (0.1%)
    Fall 24/3772 (0.6%) 19/3782 (0.5%)
    Femoral neck fracture 9/3772 (0.2%) 6/3782 (0.2%)
    Femur fracture 15/3772 (0.4%) 19/3782 (0.5%)
    Foot fracture 2/3772 (0.1%) 1/3782 (0%)
    Fracture 0/3772 (0%) 2/3782 (0.1%)
    Fracture displacement 0/3772 (0%) 1/3782 (0%)
    Fractured coccyx 2/3772 (0.1%) 0/3782 (0%)
    Fractured sacrum 2/3772 (0.1%) 0/3782 (0%)
    Graft complication 0/3772 (0%) 1/3782 (0%)
    Haematuria traumatic 1/3772 (0%) 0/3782 (0%)
    Head injury 7/3772 (0.2%) 1/3782 (0%)
    Heat exhaustion 1/3772 (0%) 0/3782 (0%)
    Hip fracture 12/3772 (0.3%) 18/3782 (0.5%)
    Humerus fracture 3/3772 (0.1%) 1/3782 (0%)
    Implantable defibrillator malfunction 1/3772 (0%) 0/3782 (0%)
    Injury 6/3772 (0.2%) 3/3782 (0.1%)
    Joint dislocation 2/3772 (0.1%) 2/3782 (0.1%)
    Joint injury 0/3772 (0%) 2/3782 (0.1%)
    Joint sprain 1/3772 (0%) 0/3782 (0%)
    Limb injury 1/3772 (0%) 0/3782 (0%)
    Lower limb fracture 0/3772 (0%) 1/3782 (0%)
    Lumbar vertebral fracture 1/3772 (0%) 3/3782 (0.1%)
    Multiple fractures 0/3772 (0%) 1/3782 (0%)
    Muscle rupture 2/3772 (0.1%) 0/3782 (0%)
    Open fracture 1/3772 (0%) 1/3782 (0%)
    Open wound 0/3772 (0%) 1/3782 (0%)
    Operative haemorrhage 3/3772 (0.1%) 2/3782 (0.1%)
    Overdose 1/3772 (0%) 2/3782 (0.1%)
    Pacemaker complication 0/3772 (0%) 2/3782 (0.1%)
    Patella fracture 1/3772 (0%) 0/3782 (0%)
    Pelvic fracture 2/3772 (0.1%) 2/3782 (0.1%)
    Pharyngeal injury 0/3772 (0%) 1/3782 (0%)
    Poisoning 0/3772 (0%) 1/3782 (0%)
    Post procedural complication 2/3772 (0.1%) 0/3782 (0%)
    Post procedural haematoma 3/3772 (0.1%) 2/3782 (0.1%)
    Post procedural haematuria 1/3772 (0%) 0/3782 (0%)
    Post procedural haemorrhage 10/3772 (0.3%) 10/3782 (0.3%)
    Post-traumatic pain 0/3772 (0%) 1/3782 (0%)
    Postoperative adhesion 1/3772 (0%) 0/3782 (0%)
    Postoperative ileus 1/3772 (0%) 0/3782 (0%)
    Postoperative renal failure 0/3772 (0%) 1/3782 (0%)
    Procedural pain 1/3772 (0%) 1/3782 (0%)
    Pubic rami fracture 1/3772 (0%) 0/3782 (0%)
    Radiation mucositis 1/3772 (0%) 0/3782 (0%)
    Radius fracture 1/3772 (0%) 0/3782 (0%)
    Rib fracture 9/3772 (0.2%) 3/3782 (0.1%)
    Road traffic accident 1/3772 (0%) 1/3782 (0%)
    Scapula fracture 0/3772 (0%) 1/3782 (0%)
    Skin laceration 1/3772 (0%) 0/3782 (0%)
    Skull fracture 0/3772 (0%) 1/3782 (0%)
    Spinal compression fracture 1/3772 (0%) 0/3782 (0%)
    Spinal fracture 4/3772 (0.1%) 6/3782 (0.2%)
    Subcutaneous haematoma 1/3772 (0%) 0/3782 (0%)
    Subdural haematoma 14/3772 (0.4%) 3/3782 (0.1%)
    Subdural haemorrhage 1/3772 (0%) 0/3782 (0%)
    Tendon injury 0/3772 (0%) 1/3782 (0%)
    Tendon rupture 1/3772 (0%) 2/3782 (0.1%)
    Therapeutic agent toxicity 9/3772 (0.2%) 8/3782 (0.2%)
    Thermal burn 1/3772 (0%) 0/3782 (0%)
    Thoracic vertebral fracture 0/3772 (0%) 1/3782 (0%)
    Tibia fracture 4/3772 (0.1%) 1/3782 (0%)
    Traumatic brain injury 1/3772 (0%) 0/3782 (0%)
    Traumatic haematoma 1/3772 (0%) 1/3782 (0%)
    Traumatic haemorrhage 1/3772 (0%) 1/3782 (0%)
    Traumatic intracranial haemorrhage 3/3772 (0.1%) 1/3782 (0%)
    Upper limb fracture 7/3772 (0.2%) 4/3782 (0.1%)
    Wound 2/3772 (0.1%) 0/3782 (0%)
    Wound complication 1/3772 (0%) 0/3782 (0%)
    Wrist fracture 2/3772 (0.1%) 1/3782 (0%)
    Investigations
    Aspiration bronchial 0/3772 (0%) 1/3782 (0%)
    Carbohydrate tolerance decreased 1/3772 (0%) 0/3782 (0%)
    Haemoglobin decreased 1/3772 (0%) 1/3782 (0%)
    International normalised ratio increased 1/3772 (0%) 0/3782 (0%)
    Prostatic specific antigen increased 1/3772 (0%) 0/3782 (0%)
    Weight decreased 3/3772 (0.1%) 0/3782 (0%)
    Metabolism and nutrition disorders
    Cachexia 1/3772 (0%) 0/3782 (0%)
    Dehydration 19/3772 (0.5%) 13/3782 (0.3%)
    Diabetes mellitus 0/3772 (0%) 1/3782 (0%)
    Diabetes mellitus inadequate control 1/3772 (0%) 1/3782 (0%)
    Electrolyte imbalance 1/3772 (0%) 0/3782 (0%)
    Failure to thrive 1/3772 (0%) 0/3782 (0%)
    Gout 4/3772 (0.1%) 3/3782 (0.1%)
    Haemosiderosis 1/3772 (0%) 0/3782 (0%)
    Hypercalcaemia 0/3772 (0%) 1/3782 (0%)
    Hyperkalaemia 5/3772 (0.1%) 1/3782 (0%)
    Hypoalbuminaemia 1/3772 (0%) 0/3782 (0%)
    Hypoglycaemia 1/3772 (0%) 2/3782 (0.1%)
    Hypokalaemia 2/3772 (0.1%) 2/3782 (0.1%)
    Hyponatraemia 4/3772 (0.1%) 9/3782 (0.2%)
    Hypovolaemia 2/3772 (0.1%) 1/3782 (0%)
    Iron deficiency 0/3772 (0%) 1/3782 (0%)
    Malnutrition 0/3772 (0%) 1/3782 (0%)
    Metabolic disorder 0/3772 (0%) 1/3782 (0%)
    Obesity 0/3772 (0%) 2/3782 (0.1%)
    Starvation 1/3772 (0%) 0/3782 (0%)
    Underweight 0/3772 (0%) 1/3782 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/3772 (0%) 3/3782 (0.1%)
    Arthritis 3/3772 (0.1%) 3/3782 (0.1%)
    Back pain 2/3772 (0.1%) 9/3782 (0.2%)
    Bunion 0/3772 (0%) 1/3782 (0%)
    Bursitis 1/3772 (0%) 0/3782 (0%)
    Chondrocalcinosis pyrophosphate 0/3772 (0%) 1/3782 (0%)
    Dupuytren's contracture 2/3772 (0.1%) 0/3782 (0%)
    Finger deformity 0/3772 (0%) 1/3782 (0%)
    Foot deformity 1/3772 (0%) 0/3782 (0%)
    Gouty arthritis 0/3772 (0%) 2/3782 (0.1%)
    Intervertebral disc degeneration 0/3772 (0%) 1/3782 (0%)
    Intervertebral disc disorder 1/3772 (0%) 0/3782 (0%)
    Intervertebral disc protrusion 5/3772 (0.1%) 3/3782 (0.1%)
    Lumbar spinal stenosis 2/3772 (0.1%) 3/3782 (0.1%)
    Mobility decreased 1/3772 (0%) 1/3782 (0%)
    Muscular weakness 0/3772 (0%) 1/3782 (0%)
    Musculoskeletal chest pain 6/3772 (0.2%) 3/3782 (0.1%)
    Musculoskeletal pain 2/3772 (0.1%) 1/3782 (0%)
    Myalgia 0/3772 (0%) 1/3782 (0%)
    Osteoarthritis 28/3772 (0.7%) 36/3782 (1%)
    Osteochondrosis 0/3772 (0%) 1/3782 (0%)
    Osteoporosis 3/3772 (0.1%) 2/3782 (0.1%)
    Osteoporotic fracture 2/3772 (0.1%) 0/3782 (0%)
    Pain in extremity 2/3772 (0.1%) 1/3782 (0%)
    Pathological fracture 0/3772 (0%) 1/3782 (0%)
    Periarthritis 1/3772 (0%) 0/3782 (0%)
    Periostitis 1/3772 (0%) 0/3782 (0%)
    Polymyalgia rheumatica 0/3772 (0%) 2/3782 (0.1%)
    Rhabdomyolysis 0/3772 (0%) 2/3782 (0.1%)
    Rheumatoid arthritis 1/3772 (0%) 1/3782 (0%)
    Senile osteoporosis 0/3772 (0%) 1/3782 (0%)
    Spinal column stenosis 1/3772 (0%) 4/3782 (0.1%)
    Spinal osteoarthritis 2/3772 (0.1%) 7/3782 (0.2%)
    Spondylolisthesis 1/3772 (0%) 0/3782 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Abdominal neoplasm 1/3772 (0%) 1/3782 (0%)
    Acute leukaemia 0/3772 (0%) 1/3782 (0%)
    Acute myeloid leukaemia 0/3772 (0%) 1/3782 (0%)
    Adenocarcinoma 1/3772 (0%) 1/3782 (0%)
    Adenocarcinoma pancreas 1/3772 (0%) 0/3782 (0%)
    Adrenal neoplasm 1/3772 (0%) 1/3782 (0%)
    B-cell lymphoma 1/3772 (0%) 2/3782 (0.1%)
    Basal cell carcinoma 4/3772 (0.1%) 3/3782 (0.1%)
    Basosquamous carcinoma 1/3772 (0%) 0/3782 (0%)
    Benign anorectal neoplasm 1/3772 (0%) 0/3782 (0%)
    Benign lung neoplasm 0/3772 (0%) 1/3782 (0%)
    Benign neoplasm of bladder 0/3772 (0%) 1/3782 (0%)
    Benign ovarian tumour 0/3772 (0%) 1/3782 (0%)
    Bile duct cancer 0/3772 (0%) 1/3782 (0%)
    Biliary cancer metastatic 0/3772 (0%) 1/3782 (0%)
    Biliary neoplasm 1/3772 (0%) 0/3782 (0%)
    Bladder cancer 3/3772 (0.1%) 3/3782 (0.1%)
    Bladder cancer recurrent 1/3772 (0%) 0/3782 (0%)
    Bladder neoplasm 5/3772 (0.1%) 2/3782 (0.1%)
    Bladder papilloma 0/3772 (0%) 2/3782 (0.1%)
    Bladder transitional cell carcinoma 1/3772 (0%) 0/3782 (0%)
    Bone sarcoma 1/3772 (0%) 1/3782 (0%)
    Brain neoplasm 2/3772 (0.1%) 3/3782 (0.1%)
    Brain neoplasm malignant 1/3772 (0%) 0/3782 (0%)
    Breast cancer 9/3772 (0.2%) 13/3782 (0.3%)
    Breast cancer female 1/3772 (0%) 0/3782 (0%)
    Breast cancer recurrent 1/3772 (0%) 0/3782 (0%)
    Breast neoplasm 0/3772 (0%) 1/3782 (0%)
    Bronchial carcinoma 0/3772 (0%) 1/3782 (0%)
    Bronchioloalveolar carcinoma 0/3772 (0%) 1/3782 (0%)
    Cancer pain 1/3772 (0%) 0/3782 (0%)
    Carcinoid tumour of the stomach 0/3772 (0%) 1/3782 (0%)
    Cervix carcinoma 1/3772 (0%) 0/3782 (0%)
    Cholesteatoma 1/3772 (0%) 0/3782 (0%)
    Chronic lymphocytic leukaemia 2/3772 (0.1%) 0/3782 (0%)
    Colon adenoma 1/3772 (0%) 0/3782 (0%)
    Colon cancer 13/3772 (0.3%) 11/3782 (0.3%)
    Colon cancer metastatic 2/3772 (0.1%) 1/3782 (0%)
    Colon cancer stage iv 1/3772 (0%) 0/3782 (0%)
    Colon neoplasm 0/3772 (0%) 5/3782 (0.1%)
    Colorectal cancer 0/3772 (0%) 2/3782 (0.1%)
    Colorectal cancer metastatic 0/3772 (0%) 1/3782 (0%)
    Cystosarcoma phyllodes 1/3772 (0%) 0/3782 (0%)
    Diffuse large b-cell lymphoma 1/3772 (0%) 0/3782 (0%)
    Duodenal neoplasm 1/3772 (0%) 0/3782 (0%)
    Endometrial cancer 1/3772 (0%) 2/3782 (0.1%)
    Endometrial cancer metastatic 1/3772 (0%) 0/3782 (0%)
    Gallbladder cancer 1/3772 (0%) 4/3782 (0.1%)
    Gastric cancer 10/3772 (0.3%) 5/3782 (0.1%)
    Gastric neoplasm 1/3772 (0%) 1/3782 (0%)
    Gastrointestinal carcinoma 0/3772 (0%) 1/3782 (0%)
    Gastrointestinal stromal tumour 1/3772 (0%) 0/3782 (0%)
    Glioblastoma 1/3772 (0%) 0/3782 (0%)
    Glioblastoma multiforme 0/3772 (0%) 1/3782 (0%)
    Glioma 1/3772 (0%) 0/3782 (0%)
    Haemangioma of liver 1/3772 (0%) 0/3782 (0%)
    Hepatic neoplasm malignant 2/3772 (0.1%) 0/3782 (0%)
    Intestinal adenocarcinoma 1/3772 (0%) 0/3782 (0%)
    Large cell carcinoma of the respiratory tract stage unspecified 1/3772 (0%) 0/3782 (0%)
    Large granular lymphocytosis 1/3772 (0%) 0/3782 (0%)
    Large intestine carcinoma 0/3772 (0%) 1/3782 (0%)
    Laryngeal cancer 1/3772 (0%) 1/3782 (0%)
    Leiomyoma 0/3772 (0%) 1/3782 (0%)
    Leiomyosarcoma 1/3772 (0%) 0/3782 (0%)
    Lipoma 1/3772 (0%) 0/3782 (0%)
    Lung adenocarcinoma 5/3772 (0.1%) 3/3782 (0.1%)
    Lung neoplasm 2/3772 (0.1%) 1/3782 (0%)
    Lung neoplasm malignant 8/3772 (0.2%) 11/3782 (0.3%)
    Lung squamous cell carcinoma stage unspecified 0/3772 (0%) 1/3782 (0%)
    Lymph node cancer metastatic 1/3772 (0%) 0/3782 (0%)
    Lymphocytic leukaemia 1/3772 (0%) 0/3782 (0%)
    Lymphoma 1/3772 (0%) 0/3782 (0%)
    Malignant melanoma 3/3772 (0.1%) 4/3782 (0.1%)
    Malignant melanoma in situ 1/3772 (0%) 0/3782 (0%)
    Malignant soft tissue neoplasm 1/3772 (0%) 0/3782 (0%)
    Mediastinum neoplasm 0/3772 (0%) 1/3782 (0%)
    Meningioma 1/3772 (0%) 0/3782 (0%)
    Metastases to adrenals 1/3772 (0%) 0/3782 (0%)
    Metastases to bone 1/3772 (0%) 1/3782 (0%)
    Metastases to central nervous system 1/3772 (0%) 3/3782 (0.1%)
    Metastases to liver 1/3772 (0%) 1/3782 (0%)
    Metastases to lung 2/3772 (0.1%) 1/3782 (0%)
    Metastatic gastric cancer 1/3772 (0%) 1/3782 (0%)
    Metastatic neoplasm 3/3772 (0.1%) 2/3782 (0.1%)
    Metastatic squamous cell carcinoma 0/3772 (0%) 1/3782 (0%)
    Multiple myeloma 1/3772 (0%) 5/3782 (0.1%)
    Myelodysplastic syndrome 7/3772 (0.2%) 2/3782 (0.1%)
    Myelofibrosis 1/3772 (0%) 0/3782 (0%)
    Nasal neoplasm 0/3772 (0%) 1/3782 (0%)
    Neoplasm malignant 2/3772 (0.1%) 0/3782 (0%)
    Neoplasm skin 0/3772 (0%) 1/3782 (0%)
    Neurilemmoma 1/3772 (0%) 0/3782 (0%)
    Neuroendocrine carcinoma 1/3772 (0%) 1/3782 (0%)
    Neuroendocrine carcinoma of the skin 1/3772 (0%) 0/3782 (0%)
    Neuroma 1/3772 (0%) 0/3782 (0%)
    Non-Hodgkin's lymphoma 3/3772 (0.1%) 4/3782 (0.1%)
    Non-small cell lung cancer 1/3772 (0%) 3/3782 (0.1%)
    Non-small cell lung cancer stage IV 1/3772 (0%) 0/3782 (0%)
    Oesophageal adenocarcinoma 1/3772 (0%) 0/3782 (0%)
    Oesophageal carcinoma 4/3772 (0.1%) 2/3782 (0.1%)
    Oral neoplasm 1/3772 (0%) 0/3782 (0%)
    Ovarian cancer 0/3772 (0%) 1/3782 (0%)
    Pancreatic carcinoma 1/3772 (0%) 8/3782 (0.2%)
    Pancreatic carcinoma metastatic 0/3772 (0%) 1/3782 (0%)
    Pancreatic neoplasm 2/3772 (0.1%) 0/3782 (0%)
    Pancreatic neuroendocrine tumour 1/3772 (0%) 0/3782 (0%)
    Papilloma 0/3772 (0%) 1/3782 (0%)
    Pelvic neoplasm 0/3772 (0%) 1/3782 (0%)
    Penis carcinoma 0/3772 (0%) 1/3782 (0%)
    Peritoneal carcinoma 0/3772 (0%) 1/3782 (0%)
    Pharyngeal cancer stage unspecified 1/3772 (0%) 0/3782 (0%)
    Pituitary tumour benign 1/3772 (0%) 0/3782 (0%)
    Plasmacytoma 1/3772 (0%) 0/3782 (0%)
    Pleural mesothelioma 1/3772 (0%) 0/3782 (0%)
    Prostate cancer 24/3772 (0.6%) 16/3782 (0.4%)
    Prostate cancer metastatic 2/3772 (0.1%) 1/3782 (0%)
    Prostatic adenoma 5/3772 (0.1%) 6/3782 (0.2%)
    Rectal cancer 3/3772 (0.1%) 8/3782 (0.2%)
    Rectal cancer metastatic 0/3772 (0%) 1/3782 (0%)
    Rectosigmoid cancer 1/3772 (0%) 1/3782 (0%)
    Renal cancer 1/3772 (0%) 3/3782 (0.1%)
    Renal cancer metastatic 2/3772 (0.1%) 1/3782 (0%)
    Renal cell carcinoma 1/3772 (0%) 0/3782 (0%)
    Renal neoplasm 0/3772 (0%) 1/3782 (0%)
    Salivary gland adenoma 1/3772 (0%) 1/3782 (0%)
    Salivary gland neoplasm 1/3772 (0%) 1/3782 (0%)
    Sarcoma uterus 1/3772 (0%) 0/3782 (0%)
    Skin cancer 2/3772 (0.1%) 1/3782 (0%)
    Small intestine carcinoma 1/3772 (0%) 0/3782 (0%)
    Squamous cell carcinoma 4/3772 (0.1%) 6/3782 (0.2%)
    Squamous cell carcinoma of skin 1/3772 (0%) 2/3782 (0.1%)
    Thyroid adenoma 1/3772 (0%) 0/3782 (0%)
    Thyroid cancer 1/3772 (0%) 2/3782 (0.1%)
    Thyroid neoplasm 0/3772 (0%) 1/3782 (0%)
    Tongue neoplasm malignant stage unspecified 1/3772 (0%) 0/3782 (0%)
    Transitional cell carcinoma 1/3772 (0%) 2/3782 (0.1%)
    Tumour haemorrhage 1/3772 (0%) 0/3782 (0%)
    Uterine cancer 1/3772 (0%) 1/3782 (0%)
    Uterine leiomyoma 2/3772 (0.1%) 0/3782 (0%)
    Vulval cancer 0/3772 (0%) 1/3782 (0%)
    Nervous system disorders
    Amyotrophic lateral sclerosis 0/3772 (0%) 1/3782 (0%)
    Ataxia 0/3772 (0%) 1/3782 (0%)
    Balance disorder 1/3772 (0%) 1/3782 (0%)
    Carpal tunnel syndrome 4/3772 (0.1%) 0/3782 (0%)
    Cauda equina syndrome 0/3772 (0%) 1/3782 (0%)
    Cerebral artery occlusion 0/3772 (0%) 1/3782 (0%)
    Cerebral disorder 2/3772 (0.1%) 0/3782 (0%)
    Cerebral haematoma 2/3772 (0.1%) 0/3782 (0%)
    Cerebral haemorrhage 2/3772 (0.1%) 1/3782 (0%)
    Cerebrovascular accident 1/3772 (0%) 2/3782 (0.1%)
    Cerebrovascular disorder 1/3772 (0%) 0/3782 (0%)
    Cervical root pain 0/3772 (0%) 2/3782 (0.1%)
    Cognitive disorder 3/3772 (0.1%) 0/3782 (0%)
    Convulsion 3/3772 (0.1%) 4/3782 (0.1%)
    Dementia 4/3772 (0.1%) 3/3782 (0.1%)
    Dementia Alzheimer's type 4/3772 (0.1%) 1/3782 (0%)
    Dizziness 5/3772 (0.1%) 8/3782 (0.2%)
    Dizziness postural 1/3772 (0%) 1/3782 (0%)
    Encephalitis 1/3772 (0%) 0/3782 (0%)
    Encephalopathy 0/3772 (0%) 2/3782 (0.1%)
    Epilepsy 5/3772 (0.1%) 4/3782 (0.1%)
    Extrapyramidal disorder 0/3772 (0%) 1/3782 (0%)
    Facial paresis 1/3772 (0%) 0/3782 (0%)
    Grand mal convulsion 1/3772 (0%) 1/3782 (0%)
    Guillain-barre syndrome 0/3772 (0%) 1/3782 (0%)
    Haemorrhage intracranial 2/3772 (0.1%) 3/3782 (0.1%)
    Haemorrhagic stroke 17/3772 (0.5%) 10/3782 (0.3%)
    Haemorrhagic transformation stroke 1/3772 (0%) 4/3782 (0.1%)
    Headache 2/3772 (0.1%) 1/3782 (0%)
    Hydrocephalus 1/3772 (0%) 0/3782 (0%)
    Hypokinesia 0/3772 (0%) 1/3782 (0%)
    Intercostal neuralgia 1/3772 (0%) 2/3782 (0.1%)
    Intracranial haematoma 0/3772 (0%) 1/3782 (0%)
    Ivth nerve paralysis 1/3772 (0%) 0/3782 (0%)
    Loss of consciousness 1/3772 (0%) 1/3782 (0%)
    Lumbar radiculopathy 0/3772 (0%) 1/3782 (0%)
    Mental impairment 1/3772 (0%) 0/3782 (0%)
    Mononeuropathy 1/3772 (0%) 0/3782 (0%)
    Nervous system disorder 0/3772 (0%) 1/3782 (0%)
    Neuralgia 1/3772 (0%) 0/3782 (0%)
    Neurological decompensation 0/3772 (0%) 1/3782 (0%)
    Optic neuritis 1/3772 (0%) 0/3782 (0%)
    Paraesthesia 0/3772 (0%) 2/3782 (0.1%)
    Parkinson's disease 1/3772 (0%) 3/3782 (0.1%)
    Polyneuropathy 1/3772 (0%) 4/3782 (0.1%)
    Post herpetic neuralgia 1/3772 (0%) 0/3782 (0%)
    Presyncope 1/3772 (0%) 4/3782 (0.1%)
    Radicular syndrome 1/3772 (0%) 0/3782 (0%)
    Ruptured cerebral aneurysm 0/3772 (0%) 1/3782 (0%)
    Sciatica 2/3772 (0.1%) 2/3782 (0.1%)
    Simple partial seizures 1/3772 (0%) 0/3782 (0%)
    Somnolence 0/3772 (0%) 1/3782 (0%)
    Spinal cord compression 1/3772 (0%) 1/3782 (0%)
    Status epilepticus 0/3772 (0%) 1/3782 (0%)
    Subarachnoid haemorrhage 2/3772 (0.1%) 0/3782 (0%)
    Syncope 12/3772 (0.3%) 9/3782 (0.2%)
    Syncope vasovagal 1/3772 (0%) 4/3782 (0.1%)
    Thalamus haemorrhage 1/3772 (0%) 0/3782 (0%)
    Thrombotic stroke 1/3772 (0%) 0/3782 (0%)
    Vascular dementia 1/3772 (0%) 1/3782 (0%)
    Vascular encephalopathy 4/3772 (0.1%) 1/3782 (0%)
    Vertebrobasilar insufficiency 1/3772 (0%) 0/3782 (0%)
    Psychiatric disorders
    Abnormal behaviour 1/3772 (0%) 0/3782 (0%)
    Alcohol abuse 0/3772 (0%) 1/3782 (0%)
    Alcohol withdrawal syndrome 1/3772 (0%) 0/3782 (0%)
    Alcoholism 0/3772 (0%) 1/3782 (0%)
    Bipolar i disorder 0/3772 (0%) 1/3782 (0%)
    Completed suicide 0/3772 (0%) 2/3782 (0.1%)
    Confusional state 6/3772 (0.2%) 5/3782 (0.1%)
    Delirium 0/3772 (0%) 1/3782 (0%)
    Delusion 1/3772 (0%) 0/3782 (0%)
    Delusional disorder, persecutory type 1/3772 (0%) 0/3782 (0%)
    Depression 11/3772 (0.3%) 5/3782 (0.1%)
    Hallucination 0/3772 (0%) 1/3782 (0%)
    Major depression 2/3772 (0.1%) 1/3782 (0%)
    Mental disorder 0/3772 (0%) 2/3782 (0.1%)
    Mental status changes 0/3772 (0%) 1/3782 (0%)
    Neurosis 0/3772 (0%) 1/3782 (0%)
    Panic disorder 0/3772 (0%) 1/3782 (0%)
    Psychotic disorder 0/3772 (0%) 2/3782 (0.1%)
    Schizophrenia 1/3772 (0%) 0/3782 (0%)
    Schizophrenia, paranoid type 1/3772 (0%) 0/3782 (0%)
    Renal and urinary disorders
    Anuria 1/3772 (0%) 0/3782 (0%)
    Bladder neck sclerosis 0/3772 (0%) 1/3782 (0%)
    Bladder obstruction 0/3772 (0%) 1/3782 (0%)
    Bladder stenosis 1/3772 (0%) 0/3782 (0%)
    Calculus bladder 1/3772 (0%) 1/3782 (0%)
    Calculus ureteric 2/3772 (0.1%) 2/3782 (0.1%)
    Calculus urinary 1/3772 (0%) 1/3782 (0%)
    Cystitis haemorrhagic 1/3772 (0%) 0/3782 (0%)
    Cystitis noninfective 2/3772 (0.1%) 0/3782 (0%)
    Cystitis ulcerative 1/3772 (0%) 0/3782 (0%)
    Dysuria 1/3772 (0%) 0/3782 (0%)
    Enuresis 0/3772 (0%) 1/3782 (0%)
    Glomerulonephritis 0/3772 (0%) 1/3782 (0%)
    Glomerulonephritis chronic 0/3772 (0%) 1/3782 (0%)
    Haematuria 10/3772 (0.3%) 4/3782 (0.1%)
    Haemorrhage urinary tract 4/3772 (0.1%) 1/3782 (0%)
    Hydronephrosis 1/3772 (0%) 1/3782 (0%)
    Nephrolithiasis 2/3772 (0.1%) 2/3782 (0.1%)
    Nephropathy 0/3772 (0%) 1/3782 (0%)
    Obstructive uropathy 0/3772 (0%) 1/3782 (0%)
    Polyuria 0/3772 (0%) 1/3782 (0%)
    Proteinuria 0/3772 (0%) 1/3782 (0%)
    Renal artery stenosis 1/3772 (0%) 0/3782 (0%)
    Renal colic 4/3772 (0.1%) 1/3782 (0%)
    Renal cyst 2/3772 (0.1%) 0/3782 (0%)
    Renal disorder 1/3772 (0%) 0/3782 (0%)
    Renal failure 16/3772 (0.4%) 14/3782 (0.4%)
    Renal failure acute 22/3772 (0.6%) 23/3782 (0.6%)
    Renal failure chronic 3/3772 (0.1%) 5/3782 (0.1%)
    Renal haemorrhage 1/3772 (0%) 0/3782 (0%)
    Renal impairment 3/3772 (0.1%) 4/3782 (0.1%)
    Ureteric obstruction 0/3772 (0%) 1/3782 (0%)
    Urethral fistula 2/3772 (0.1%) 0/3782 (0%)
    Urethral meatus stenosis 1/3772 (0%) 1/3782 (0%)
    Urethral stenosis 4/3772 (0.1%) 6/3782 (0.2%)
    Urinary bladder haemorrhage 2/3772 (0.1%) 0/3782 (0%)
    Urinary bladder polyp 1/3772 (0%) 1/3782 (0%)
    Urinary incontinence 1/3772 (0%) 1/3782 (0%)
    Urinary retention 11/3772 (0.3%) 2/3782 (0.1%)
    Urinary tract disorder 1/3772 (0%) 0/3782 (0%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 12/3772 (0.3%) 13/3782 (0.3%)
    Breast mass 1/3772 (0%) 0/3782 (0%)
    Cervical dysplasia 0/3772 (0%) 1/3782 (0%)
    Colpocele 0/3772 (0%) 1/3782 (0%)
    Endometrial atrophy 0/3772 (0%) 1/3782 (0%)
    Endometrial hyperplasia 1/3772 (0%) 2/3782 (0.1%)
    Endometrial hypertrophy 0/3772 (0%) 1/3782 (0%)
    Fibrocystic breast disease 0/3772 (0%) 1/3782 (0%)
    Gynaecomastia 0/3772 (0%) 1/3782 (0%)
    Ovarian cyst 2/3772 (0.1%) 1/3782 (0%)
    Prostatic disorder 0/3772 (0%) 1/3782 (0%)
    Prostatic haemorrhage 1/3772 (0%) 0/3782 (0%)
    Prostatism 1/3772 (0%) 2/3782 (0.1%)
    Prostatitis 4/3772 (0.1%) 3/3782 (0.1%)
    Prostatomegaly 0/3772 (0%) 3/3782 (0.1%)
    Rectocele 1/3772 (0%) 0/3782 (0%)
    Uterine enlargement 0/3772 (0%) 1/3782 (0%)
    Uterine haemorrhage 1/3772 (0%) 1/3782 (0%)
    Uterine polyp 2/3772 (0.1%) 0/3782 (0%)
    Uterine prolapse 1/3772 (0%) 1/3782 (0%)
    Vaginal cyst 0/3772 (0%) 1/3782 (0%)
    Vaginal haemorrhage 1/3772 (0%) 0/3782 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema 1/3772 (0%) 0/3782 (0%)
    Acute respiratory distress syndrome 1/3772 (0%) 2/3782 (0.1%)
    Acute respiratory failure 2/3772 (0.1%) 4/3782 (0.1%)
    Alveolitis 1/3772 (0%) 0/3782 (0%)
    Asthma 5/3772 (0.1%) 4/3782 (0.1%)
    Atelectasis 0/3772 (0%) 2/3782 (0.1%)
    Bronchial disorder 0/3772 (0%) 2/3782 (0.1%)
    Bronchitis chronic 7/3772 (0.2%) 7/3782 (0.2%)
    Bronchopneumopathy 0/3772 (0%) 1/3782 (0%)
    Bronchospasm 1/3772 (0%) 0/3782 (0%)
    Chronic obstructive pulmonary disease 28/3772 (0.7%) 27/3782 (0.7%)
    Cough 0/3772 (0%) 2/3782 (0.1%)
    Dyspnoea 0/3772 (0%) 3/3782 (0.1%)
    Dyspnoea exertional 1/3772 (0%) 0/3782 (0%)
    Epistaxis 17/3772 (0.5%) 7/3782 (0.2%)
    Haemoptysis 2/3772 (0.1%) 2/3782 (0.1%)
    Haemothorax 0/3772 (0%) 2/3782 (0.1%)
    Interstitial lung disease 0/3772 (0%) 1/3782 (0%)
    Lung disorder 3/3772 (0.1%) 2/3782 (0.1%)
    Nasal polyps 1/3772 (0%) 0/3782 (0%)
    Pleural adhesion 1/3772 (0%) 0/3782 (0%)
    Pleural effusion 8/3772 (0.2%) 8/3782 (0.2%)
    Pleurisy 5/3772 (0.1%) 1/3782 (0%)
    Pneumonia aspiration 4/3772 (0.1%) 4/3782 (0.1%)
    Pneumonitis 0/3772 (0%) 1/3782 (0%)
    Pneumothorax 4/3772 (0.1%) 2/3782 (0.1%)
    Pulmonary congestion 0/3772 (0%) 1/3782 (0%)
    Pulmonary embolism 2/3772 (0.1%) 1/3782 (0%)
    Pulmonary fibrosis 2/3772 (0.1%) 0/3782 (0%)
    Pulmonary haemorrhage 1/3772 (0%) 1/3782 (0%)
    Pulmonary hilum mass 1/3772 (0%) 0/3782 (0%)
    Pulmonary mass 1/3772 (0%) 0/3782 (0%)
    Pulmonary oedema 0/3772 (0%) 1/3782 (0%)
    Respiratory acidosis 1/3772 (0%) 0/3782 (0%)
    Respiratory arrest 0/3772 (0%) 2/3782 (0.1%)
    Respiratory distress 0/3772 (0%) 1/3782 (0%)
    Respiratory failure 5/3772 (0.1%) 6/3782 (0.2%)
    Sleep apnoea syndrome 2/3772 (0.1%) 0/3782 (0%)
    Status asthmaticus 2/3772 (0.1%) 0/3782 (0%)
    Thoracic haemorrhage 1/3772 (0%) 0/3782 (0%)
    Tonsillar disorder 0/3772 (0%) 1/3782 (0%)
    Skin and subcutaneous tissue disorders
    Decubitus ulcer 1/3772 (0%) 1/3782 (0%)
    Dermatitis allergic 1/3772 (0%) 0/3782 (0%)
    Dermatitis atopic 0/3772 (0%) 1/3782 (0%)
    Ecchymosis 0/3772 (0%) 1/3782 (0%)
    Haemorrhage subcutaneous 1/3772 (0%) 0/3782 (0%)
    Pemphigoid 0/3772 (0%) 1/3782 (0%)
    Psoriasis 0/3772 (0%) 1/3782 (0%)
    Pustular psoriasis 0/3772 (0%) 1/3782 (0%)
    Rash 0/3772 (0%) 2/3782 (0.1%)
    Skin induration 0/3772 (0%) 1/3782 (0%)
    Skin lesion 1/3772 (0%) 0/3782 (0%)
    Skin necrosis 1/3772 (0%) 1/3782 (0%)
    Skin ulcer 2/3772 (0.1%) 1/3782 (0%)
    Skin ulcer haemorrhage 1/3772 (0%) 0/3782 (0%)
    Stasis dermatitis 1/3772 (0%) 0/3782 (0%)
    Toxic skin eruption 1/3772 (0%) 0/3782 (0%)
    Urticaria 1/3772 (0%) 0/3782 (0%)
    Social circumstances
    Bedridden 1/3772 (0%) 0/3782 (0%)
    Disability 0/3772 (0%) 1/3782 (0%)
    Elderly 1/3772 (0%) 0/3782 (0%)
    Joint prosthesis user 2/3772 (0.1%) 0/3782 (0%)
    Social problem 0/3772 (0%) 1/3782 (0%)
    Social stay hospitalisation 0/3772 (0%) 1/3782 (0%)
    Surgical and medical procedures
    Circumcision 1/3772 (0%) 0/3782 (0%)
    Haemorrhoid operation 0/3772 (0%) 1/3782 (0%)
    Hip arthroplasty 1/3772 (0%) 1/3782 (0%)
    Intestinal stoma 0/3772 (0%) 1/3782 (0%)
    Intraocular lens implant 0/3772 (0%) 1/3782 (0%)
    Obesity surgery 1/3772 (0%) 0/3782 (0%)
    Wound drainage 0/3772 (0%) 1/3782 (0%)
    Vascular disorders
    Aneurysm 1/3772 (0%) 1/3782 (0%)
    Angiodysplasia 1/3772 (0%) 0/3782 (0%)
    Aortic aneurysm 2/3772 (0.1%) 6/3782 (0.2%)
    Aortic aneurysm rupture 1/3772 (0%) 2/3782 (0.1%)
    Aortic dissection 1/3772 (0%) 1/3782 (0%)
    Aortic rupture 1/3772 (0%) 0/3782 (0%)
    Arteriosclerosis 1/3772 (0%) 1/3782 (0%)
    Arteriosclerosis obliterans 1/3772 (0%) 0/3782 (0%)
    Bleeding varicose vein 1/3772 (0%) 2/3782 (0.1%)
    Cardiovascular insufficiency 0/3772 (0%) 1/3782 (0%)
    Circulatory collapse 0/3772 (0%) 1/3782 (0%)
    Deep vein thrombosis 1/3772 (0%) 0/3782 (0%)
    Femoral artery aneurysm 0/3772 (0%) 1/3782 (0%)
    Haematoma 1/3772 (0%) 3/3782 (0.1%)
    Haemorrhage 6/3772 (0.2%) 3/3782 (0.1%)
    Hypertension 1/3772 (0%) 0/3782 (0%)
    Hypertensive crisis 0/3772 (0%) 2/3782 (0.1%)
    Hypotension 5/3772 (0.1%) 3/3782 (0.1%)
    Orthostatic hypotension 2/3772 (0.1%) 1/3782 (0%)
    Peripheral arterial occlusive disease 0/3772 (0%) 1/3782 (0%)
    Peripheral artery aneurysm 0/3772 (0%) 1/3782 (0%)
    Peripheral embolism 0/3772 (0%) 1/3782 (0%)
    Peripheral ischaemia 0/3772 (0%) 2/3782 (0.1%)
    Peripheral vascular disorder 1/3772 (0%) 0/3782 (0%)
    Thrombophlebitis 2/3772 (0.1%) 1/3782 (0%)
    Thrombosis 1/3772 (0%) 0/3782 (0%)
    Varicose ulceration 1/3772 (0%) 0/3782 (0%)
    Varicose vein 0/3772 (0%) 1/3782 (0%)
    Vasculitis 1/3772 (0%) 2/3782 (0.1%)
    Venous insufficiency 1/3772 (0%) 0/3782 (0%)
    Venous thrombosis 0/3772 (0%) 1/3782 (0%)
    Other (Not Including Serious) Adverse Events
    Clopidogrel + ASA Placebo + ASA
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2542/3772 (67.4%) 2502/3782 (66.2%)
    Cardiac disorders
    Any Cardiac disorders 301/3772 (8%) 314/3782 (8.3%)
    Eye disorders
    Any Eye disorders 190/3772 (5%) 198/3782 (5.2%)
    Gastrointestinal disorders
    Any Gastrointestinal disorders 806/3772 (21.4%) 763/3782 (20.2%)
    General disorders
    Any General disorders and administration site conditions 582/3772 (15.4%) 541/3782 (14.3%)
    Infections and infestations
    Any Infections and infestations 994/3772 (26.4%) 961/3782 (25.4%)
    Injury, poisoning and procedural complications
    Any Injury, poisoning and procedural complications 433/3772 (11.5%) 353/3782 (9.3%)
    Investigations
    Any Investigations 185/3772 (4.9%) 201/3782 (5.3%)
    Metabolism and nutrition disorders
    Any Metabolism and nutrition disorders 239/3772 (6.3%) 257/3782 (6.8%)
    Musculoskeletal and connective tissue disorders
    Any Musculoskeletal and connective tissue disorders 532/3772 (14.1%) 623/3782 (16.5%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Any Neoplasms benign, malignant and unspecified (incl cysts and polyps) 220/3772 (5.8%) 208/3782 (5.5%)
    Nervous system disorders
    Any Nervous system disorders 661/3772 (17.5%) 682/3782 (18%)
    Dizziness 300/3772 (8%) 312/3782 (8.2%)
    Renal and urinary disorders
    Any Renal and urinary disorders 184/3772 (4.9%) 196/3782 (5.2%)
    Respiratory, thoracic and mediastinal disorders
    Any Respiratory, thoracic and mediastinal disorders 538/3772 (14.3%) 510/3782 (13.5%)
    Dyspnoea 231/3772 (6.1%) 215/3782 (5.7%)
    Skin and subcutaneous tissue disorders
    Any Skin and subcutaneous tissue disorders 337/3772 (8.9%) 289/3782 (7.6%)
    Vascular disorders
    Any Vascular disorders 440/3772 (11.7%) 414/3782 (10.9%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Publication of the study will be made jointly in the name of all wholehearted collaborators. Other papers will be authored based on the contributions of the individuals to the overall study. Substudies with scientific merit which have received prior approval from the Steering Committee (SC) may be published in the names of the contributing investigators. A copy of all manuscripts will be provided to the sponsors for their review. The final decision to publish articles will be made by the SC.

    Results Point of Contact

    Name/Title International Clinical Development, Clinical Study Director
    Organization sanofi-aventis
    Phone
    Email GV-Contact-us@sanofi-aventis.com
    Responsible Party:
    Sanofi
    ClinicalTrials.gov Identifier:
    NCT00249873
    Other Study ID Numbers:
    • EFC4912 A
    First Posted:
    Nov 7, 2005
    Last Update Posted:
    Jun 15, 2015
    Last Verified:
    May 1, 2015