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Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent EveNTs/Optimal Antiplatelet Strategy for InterventionS (CURRENT/OASIS7)

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ClinicalTrials.gov Identifier: NCT00335452
Recruitment Status : Completed
First Posted : June 9, 2006
Results First Posted : October 7, 2010
Last Update Posted : November 18, 2010
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by:
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Factorial Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Acute Coronary Disease
Angina Unstable
Interventions Drug: Clopidogrel
Drug: acetylsalicyclic acid (ASA)
Enrollment 25086
Recruitment Details 25086 patients were enrolled and randomized between June 2006 and August 2009 in 597 sites in 39 countries. Because the observed overall blinded event rate was substantially lower than expected, the number of patients to be enrolled was increased from 18000 to 20000, then to 25000.
Pre-assignment Details Treatment assignment was performed through an automated voice randomization service (AreS). At the same time, the AReS provided allocation to a Clopidogrel treatment regimen according to a pre-defined randomization list and to a ASA dose according to a factorial design.
Arm/Group Title Clopidogrel 300/75/75 mg + ASA Low Dose Clopidogrel 300/75/75 mg + ASA High Dose Clopidogrel 600/150/75 mg + ASA Low Dose Clopidogrel 600/150/75 mg + ASA High Dose
Hide Arm/Group Description

Day 1: Clopidogrel 300 mg loading dose + ASA ≥ 300 mg

Day 2 to Day 7: Clopidogrel 75 mg + ASA 75-100 mg

Day 8 to Day 30: Clopidogrel 75 mg + ASA 75-100 mg

Day 1: Clopidogrel 300 mg loading dose + ASA ≥ 300 mg

Day 2 to Day 7: Clopidogrel 75 mg + ASA 300-325 mg

Day 8 to Day 30: Clopidogrel 75 mg + ASA 300-325 mg

Day 1: Clopidogrel 600 mg loading dose + ASA ≥ 300 mg

Day 2 to Day 7: Clopidogrel 150 mg + ASA 75-100 mg

Day 8 to Day 30: Clopidogrel 75 mg + ASA 75-100 mg

Day 1: Clopidogrel 600 mg loading dose + ASA ≥ 300 mg

Day 2 to Day 7: Clopidogrel 150 mg + ASA 300-325 mg

Day 8 to Day 30: Clopidogrel 75 mg + ASA 300-325 mg

Period Title: Overall Study
Started 6312 [1] 6254 [1] 6267 [1] 6253 [1]
TREATED WITH CLOPIDOGREL 6271 6218 6228 6217
TREATED WITH ASA 6302 6251 6261 6247
Completed 6154 [2] 6107 [2] 6108 [2] 6122 [2]
Not Completed 158 147 159 131
Reason Not Completed
Death             156             144             158             129
Lost to Follow-up             2             3             1             2
[1]
Randomized
[2]
Completed 30 days follow-up period
Arm/Group Title Clopidogrel 300/75/75 mg + ASA Low Dose Clopidogrel 300/75/75 mg + ASA High Dose Clopidogrel 600/150/75 mg + ASA Low Dose Clopidogrel 600/150/75 mg + ASA High Dose Total
Hide Arm/Group Description [Not Specified] [Not Specified] [Not Specified] [Not Specified] Total of all reporting groups
Overall Number of Baseline Participants 6312 6254 6267 6253 25086
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6312 participants 6254 participants 6267 participants 6253 participants 25086 participants
61.3  (11.7) 61.5  (11.7) 61.2  (11.8) 61.4  (11.9) 61.3  (11.8)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6312 participants 6254 participants 6267 participants 6253 participants 25086 participants
< 65 years 3792 3740 3787 3735 15054
65 - 74 years 1573 1576 1543 1543 6235
≥ 75 years 947 937 937 975 3796
Missing 0 1 0 0 1
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6312 participants 6254 participants 6267 participants 6253 participants 25086 participants
Female
1702
  27.0%
1756
  28.1%
1671
  26.7%
1742
  27.9%
6871
  27.4%
Male
4610
  73.0%
4498
  71.9%
4596
  73.3%
4511
  72.1%
18215
  72.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6312 participants 6254 participants 6267 participants 6253 participants 25086 participants
Argentina 182 159 162 174 677
Australia 97 100 96 95 388
Austria 41 35 35 40 151
Belgium 55 61 59 53 228
Brazil 292 275 270 288 1125
Bulgaria 111 122 125 112 470
Canada 349 379 373 347 1448
Chile 95 85 82 90 352
China 510 492 500 515 2017
Croatia 114 145 144 114 517
Czech Republic 257 275 277 258 1067
Estonia 1 0 0 1 2
Finland 132 127 127 132 518
France 177 163 165 175 680
Germany 471 450 453 470 1844
Greece 20 21 23 21 85
India 658 650 645 646 2599
Ireland 24 13 15 23 75
Israel 286 272 275 282 1115
Italy 232 260 258 231 981
Korea, Republic of 161 149 152 165 627
Latvia 16 16 15 15 62
Lithuania 26 31 30 28 115
Malaysia 29 39 39 28 135
Mexico 16 17 19 17 69
Netherlands 46 48 48 46 188
New Zealand 36 31 29 29 125
Poland 365 322 325 362 1374
Romania 47 30 33 48 158
Russian Federation 132 137 138 131 538
Singapore 10 13 15 10 48
Slovakia 93 84 83 92 352
South Africa 24 14 14 23 75
Spain 264 276 283 263 1086
Sweden 10 11 9 10 40
Switzerland 51 64 64 48 227
Turkey 79 96 94 78 347
United Kingdom 28 29 34 28 119
United States 775 763 759 765 3062
Qualifying condition  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6312 participants 6254 participants 6267 participants 6253 participants 25086 participants
Suspected Unstable Angina (UA) 1809 1771 1757 1877 7214
Suspected MI without ST elevation (NSTEMI) 2662 2662 2668 2539 10531
MI with ST elevation (STEMI) 1839 1817 1839 1832 7327
Missing 2 4 3 5 14
Intended PCI performed   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6312 participants 6254 participants 6267 participants 6253 participants 25086 participants
Yes 4377 4326 4262 4298 17263
No 1935 1928 2005 1955 7823
[1]
Measure Description: The intent to perform a PCI as early as possible and no later than 72 hours of randomization was part of the criteria for inclusion
1.Primary Outcome
Title First Occurrence of CV Death / MI / Stroke - Clopidogrel Treatment Regimen Comparison
Hide Description

The primary endpoint is the first occurrence of any of the following events:

  • Cardiovascular death (any death with a clear cardiovascular or unknown cause),
  • Myocardial Infarction (diagnosis of new Myocardial Infarction (MI) - nonfatal or fatal)
  • Stroke (presence of a new focal neurologic deficit thought to be vascular in origin, with signs or symptoms lasting more than 24 hours - nonfatal or fatal)

reported between the randomization and Day 30 (inclusive), and validated by the blinded Event Adjudication Committee (EAC).

Time Frame 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis is on the intent-to-treat population (ITT) that consists of all patients randomized irrespective of whether they received study medication, underwent a PCI, or otherwise complied with the study protocol.
Arm/Group Title Clopidogrel 300/75/75 mg + ASA Clopidogrel 600/150/75 mg + ASA
Hide Arm/Group Description:
Patients randomized to the Clopidogrel 300/75/75 mg dose regimen irrespective of the ASA dose
Patients randomized to the Clopidogrel 600/150/75 mg dose regimen irrespective of the ASA dose
Overall Number of Participants Analyzed 12566 12520
Measure Type: Number
Unit of Measure: participants
CV death/MI/Stroke 557 522
- CV death 222 226
- MI (fatal or not) 274 237
- Stroke (fatal or not) 61 59
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Clopidogrel 300/75/75 mg + ASA, Clopidogrel 600/150/75 mg + ASA
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3037
Comments The a priori threshold for statistical significance is ≤0.05.
Method Log Rank
Comments Two-sided stratified by ASA dose level (low or high) and qualifying condition (UA/NSTEMI or STEMI) log-rank test.
Method of Estimation Estimation Parameter Relative Risk Reduction (%)
Estimated Value 6.1
Confidence Interval (2-Sided) 95%
-5.8 to 16.6
Estimation Comments The relative risk reduction (high dose treatment regimen (600/150/75 mg) versus standard treatment regimen (300/75/75 mg)) is estimated using stratified Cox proportional hazards model controlling for ASA dose level and qualifying condition.
2.Primary Outcome
Title First Occurrence of CV Death / MI / Stroke - ASA Dose Comparison
Hide Description [Not Specified]
Time Frame 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis is on the the ASA treated population that consists of all patients randomized and having receiving at least one dose of ASA. All patients were included in the treatment group to which they were allocated by the AReS.
Arm/Group Title Clopidogrel + ASA Low Dose Clopidogrel + ASA High Dose
Hide Arm/Group Description:
Patients treated with ASA low dose irrespective of the Clopidogrel treatment regimen
Patients treated with ASA high dose irrespective of the Clopidogrel treatment regimen
Overall Number of Participants Analyzed 12563 12498
Measure Type: Number
Unit of Measure: participants
CV death/MI/Stroke 546 527
- CV death 231 211
- MI (fatal or not) 260 251
- Stroke (fatal or not) 55 65
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Clopidogrel + ASA Low Dose, Clopidogrel + ASA High Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6047
Comments The a priori threshold for statistical significance is ≤0.05.
Method Log Rank
Comments Two-sided stratified by clopidogrel treatment regimen (300/75/75 mg or 600/150/75 mg) log-rank test.
Method of Estimation Estimation Parameter Relative Risk Reduction (%)
Estimated Value 3.1
Confidence Interval (2-Sided) 95%
-9.2 to 14.0
Estimation Comments The relative risk reduction (ASA high dose versus ASA low dose) is estimated using stratified Cox proportional hazards model controlling for Clopidogrel treatment regimen.
3.Primary Outcome
Title First Occurrence of CV Death / MI / Stroke - Interaction Clopidogrel Treatment Regimen and ASA Dose Level
Hide Description [Not Specified]
Time Frame 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis is on the intent-to-treat population (ITT) that consists of all patients randomized irrespective of whether they received study medication, underwent a PCI, or otherwise complied with the study protocol.
Arm/Group Title Clopidogrel 300/75/75 mg + ASA Low Dose Clopidogrel 300/75/75 mg + ASA High Dose Clopidogrel 600/150/75 mg + ASA Low Dose Clopidogrel 600/150/75 mg + ASA High Dose
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 6312 6254 6267 6253
Measure Type: Number
Unit of Measure: participants
267 290 282 240
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Clopidogrel 300/75/75 mg + ASA Low Dose, Clopidogrel 600/150/75 mg + ASA Low Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4579
Comments The a priori threshold for statistical significance is ≤0.05.
Method Log Rank
Comments Two-sided stratified by qualifying condition (UA/NSTEMI or STEMI) log-rank test.
Method of Estimation Estimation Parameter Relative Risk Reduction (%)
Estimated Value -6.5
Confidence Interval (2-Sided) 95%
-26.0 to 9.9
Estimation Comments The relative risk reduction (high dose treatment regimen (600/150/75 mg) versus standard treatment regimen (300/75/75 mg)) is estimated using a stratified Cox proportional hazards model controlling for qualifying condition.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Clopidogrel 300/75/75 mg + ASA High Dose, Clopidogrel 600/150/75 mg + ASA High Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0262
Comments The a priori threshold for statistical significance is ≤0.05.
Method Log Rank
Comments Two-sided stratified by qualifying condition (UA/NSTEMI or STEMI) log-rank test.
Method of Estimation Estimation Parameter Relative Risk Reduction (%)
Estimated Value 17.6
Confidence Interval (2-Sided) 95%
2.2 to 30.5
Estimation Comments The relative risk reduction (high dose treatment regimen (600/150/75 mg) versus standard treatment regimen (300/75/75 mg)) is estimated using a stratified Cox proportional hazards model controlling for qualifying condition.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Clopidogrel 300/75/75 mg + ASA Low Dose, Clopidogrel 300/75/75 mg + ASA High Dose, Clopidogrel 600/150/75 mg + ASA Low Dose, Clopidogrel 600/150/75 mg + ASA High Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0355
Comments The a priori threshold for statistical significance is ≤0.05.
Method Chi-squared
Comments Interaction chi-squared test of the Cox proportional hazards model.
4.Primary Outcome
Title First Occurrence of CV Death / MI / Stroke - Clopidogrel Treatment Regimen Comparison in PCI Subgroup
Hide Description [Not Specified]
Time Frame 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) analysis is done on the randomized patients who underwent PCI during the study.
Arm/Group Title Clopidogrel 300/75/75 mg + ASA Clopidogrel 600/150/75 mg + ASA
Hide Arm/Group Description:
Patients randomized to the Clopidogrel 300/75/75 mg dose regimen irrespective of the ASA dose
Patients randomized to the Clopidogrel 600/150/75 mg dose regimen irrespective of the ASA dose
Overall Number of Participants Analyzed 8703 8560
Measure Type: Number
Unit of Measure: participants
CV death/MI/Stroke 392 330
- CV death 132 130
- MI (fatal or not) 225 172
- Stroke (fatal or not) 35 28
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Clopidogrel 300/75/75 mg + ASA, Clopidogrel 600/150/75 mg + ASA
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0332
Comments The a priori threshold for statistical significance is ≤0.05.
Method Log Rank
Comments Two-sided stratified by ASA dose level (low or high) and qualifying condition (UA/NSTEMI or STEMI) Log-rank test. No adjustment was made.
Method of Estimation Estimation Parameter Relative Risk Reduction (%)
Estimated Value 14.7
Confidence Interval (2-Sided) 95%
1.2 to 26.3
Estimation Comments The relative risk reduction (high dose treatment regimen (600/150/75 mg) versus standard treatment regimen (300/75/75 mg)) is estimated using a stratified Cox proportional hazards model controlling for ASA dose level and qualifying condition.
5.Secondary Outcome
Title Occurrence of Major Bleeding - Clopidogrel Dose Regimen Comparison
Hide Description Major bleeding is defined as any severe bleeding (associated with any of the following: death, leading to a drop in hemoglobin ≥ 5 g/dl, significant hypotension with the need for inotropic agents, symptomatic intracranial hemorrhage, requirement for surgery or for a transfusion ≥ 4 units of red blood cells or equivalent whole blood) and other major bleeding (significantly disabling bleeding, or intraocular bleeding leading to significant loss of vision or bleeding requiring transfusion of 2-3 units of red blood cells or equivalent whole blood) after validation by the independent EAC.
Time Frame 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis is on the intent-to-treat population (ITT) that consists of all patients randomized irrespective of whether they received study medication, underwent a PCI, or otherwise complied with the study protocol.
Arm/Group Title Clopidogrel 300/75/75 mg + ASA Clopidogrel 600/150/75 mg + ASA
Hide Arm/Group Description:
Patients randomized to the Clopidogrel 300/75/75 mg dose regimen irrespective of the ASA dose
Patients randomized to the Clopidogrel 600/150/75 mg dose regimen irrespective of the ASA dose.
Overall Number of Participants Analyzed 12566 12520
Measure Type: Number
Unit of Measure: participants
Major bleeding 255 313
- Severe bleeding 195 236
- Major but not severe bleeding 65 83
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Clopidogrel 300/75/75 mg + ASA, Clopidogrel 600/150/75 mg + ASA
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments The a priori threshold for statistical significance is ≤0.05.
Method Regression, Logistic
Comments logistic regression model including terms for ASA dose level (low or high) and qualifying condition (UA/NSTEMI or STEMI).
6.Secondary Outcome
Title Occurrence of Major Bleeding - ASA Dose Level Comparison
Hide Description [Not Specified]
Time Frame 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis is on the treated patient population that consists of all patients randomized and having receiving at least one dose of ASA. All patients were included in the treatment group to which they were allocated by the AReS.
Arm/Group Title Clopidogrel + ASA Low Dose Clopidogrel + ASA High Dose
Hide Arm/Group Description:
Patients treated with ASA low dose irrespective of the Clopidogrel treatment regimen
Patients treated with ASA high dose irrespective of the Clopidogrel treatment regimen
Overall Number of Participants Analyzed 12563 12498
Measure Type: Number
Unit of Measure: participants
Major bleeding 285 282
- Severe bleeding 215 216
- Major but not severe bleeding 74 73
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Clopidogrel + ASA Low Dose, Clopidogrel + ASA High Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.945
Comments The a priori threshold for statistical significance is ≤0.05.
Method Regression, Logistic
Comments Logistic regression model including a term for Clopidogrel treatment regimen (300/75/75 mg or 600/150/75 mg).
7.Post-Hoc Outcome
Title Occurrence of Stent Thrombosis - Clopidogrel Treatment Regimen Comparison
Hide Description This includes definite stent thrombosis (confirmed by angiography or evidence of recent thrombus determined at autopsy or by examination of tissue retrieved following thrombectomy) and probable stent thrombosis (unexplained death having occurred after intracoronary stenting or, MI related to acute ischemia in the territory of the implanted stent without angiographic confirmation and in the absence of any obvious cause) after validation by the EAC.
Time Frame 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis is on the intent-to-treat population (ITT) that consists of all patients randomized irrespective of whether they received study medication, underwent a PCI, or otherwise complied with the study protocol.
Arm/Group Title Clopidogrel 300/75/75 mg + ASA Clopidogrel 600/150/75 mg + ASA
Hide Arm/Group Description:
Patients randomized to the Clopidogrel 300/75/75 mg dose regimen irrespective of the ASA dose
Patients randomized to the Clopidogrel 600/150/75 mg dose regimen irrespective of the ASA dose
Overall Number of Participants Analyzed 12566 12520
Measure Type: Number
Unit of Measure: participants
Stent trombosis 200 135
- Definite 111 58
- Probable 89 77
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Clopidogrel 300/75/75 mg + ASA, Clopidogrel 600/150/75 mg + ASA
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments The a priori threshold for statistical significance is ≤0.05.
Method Log Rank
Comments Two-sided stratified by ASA dose level (low or high) and qualifying condition (UA/NSTEMI or STEMI) log-rank test.
Method of Estimation Estimation Parameter Relative Risk Reduction (%)
Estimated Value 32.6
Confidence Interval (2-Sided) 95%
16.2 to 45.8
Estimation Comments The relative risk reduction (high dose treatment regimen (600/150/75 mg) versus standard treatment regimen (300/75/75 mg)) is estimated using a stratified Cox proportional hazards model controlling for ASA dose level and qualifying condition.
Time Frame 30 days
Adverse Event Reporting Description

The analysis is on the intent-to-treat population (ITT). All patients were included in the treatment arm to which they were allocated by the AReS.

Any adverse event that developed or worsened on or after randomization up to the day of the final follow-up visit was included.

 
Arm/Group Title Clopidogrel 300/75/75 mg + ASA Low Dose Clopidogrel 300/75/75 mg + ASA High Dose Clopidogrel 600/150/75 mg + ASA Low Dose Clopidogrel 600/150/75 mg + ASA High Dose
Hide Arm/Group Description

Day 1: Clopidogrel 300 mg loading dose + ASA ≥ 300 mg

Day 2 to Day 7: Clopidogrel 75 mg + ASA 75-100 mg

Day 8 to Day 30: Clopidogrel 75 mg + ASA 75-100 mg

Day 1: Clopidogrel 300 mg loading dose + ASA ≥ 300 mg

Day 2 to Day 7: Clopidogrel 75 mg + ASA 300-325 mg

Day 8 to Day 30: Clopidogrel 75 mg + ASA 300-325 mg

Day 1: Clopidogrel 600 mg loading dose + ASA ≥ 300 mg

Day 2 to Day 7: Clopidogrel 150 mg + ASA 75-100 mg

Day 8 to Day 30: Clopidogrel 75 mg + ASA 75-100 mg

Day 1: Clopidogrel 600 mg loading dose + ASA ≥ 300 mg

Day 2 to Day 7: Clopidogrel 150 mg + ASA 300-325 mg

Day 8 to Day 30: Clopidogrel 75 mg + ASA 300-325 mg

All-Cause Mortality
Clopidogrel 300/75/75 mg + ASA Low Dose Clopidogrel 300/75/75 mg + ASA High Dose Clopidogrel 600/150/75 mg + ASA Low Dose Clopidogrel 600/150/75 mg + ASA High Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Clopidogrel 300/75/75 mg + ASA Low Dose Clopidogrel 300/75/75 mg + ASA High Dose Clopidogrel 600/150/75 mg + ASA Low Dose Clopidogrel 600/150/75 mg + ASA High Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   322/6312 (5.10%)   329/6254 (5.26%)   372/6267 (5.94%)   332/6253 (5.31%) 
Blood and lymphatic system disorders         
Haemorrhagic anaemia * 1  7/6312 (0.11%)  5/6254 (0.08%)  4/6267 (0.06%)  6/6253 (0.10%) 
Anaemia * 1  5/6312 (0.08%)  1/6254 (0.02%)  3/6267 (0.05%)  5/6253 (0.08%) 
Thrombocytopenia * 1  2/6312 (0.03%)  3/6254 (0.05%)  4/6267 (0.06%)  2/6253 (0.03%) 
Nephrogenic anaemia * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  2/6253 (0.03%) 
Heparin-induced thrombocytopenia * 1  0/6312 (0.00%)  2/6254 (0.03%)  0/6267 (0.00%)  1/6253 (0.02%) 
Anaemia of chronic disease * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Eosinophilia * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Normochromic normocytic anaemia * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Disseminated intravascular coagulation * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Iron deficiency anaemia * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
White blood cell disorder * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Lymphadenopathy * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Microcytic anaemia * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Splenic infarction * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Cardiac disorders         
Pericardial haemorrhage * 1  15/6312 (0.24%)  12/6254 (0.19%)  18/6267 (0.29%)  11/6253 (0.18%) 
Intracardiac thrombus * 1  1/6312 (0.02%)  2/6254 (0.03%)  1/6267 (0.02%)  5/6253 (0.08%) 
Pericarditis * 1  3/6312 (0.05%)  1/6254 (0.02%)  2/6267 (0.03%)  1/6253 (0.02%) 
Acute left ventricular failure * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Atrial thrombosis * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Cardiac perforation * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Cardiogenic shock * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Interventricular septum rupture * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Myopericarditis * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Mitral valve incompetence * 1  0/6312 (0.00%)  1/6254 (0.02%)  1/6267 (0.02%)  0/6253 (0.00%) 
Cardiac tamponade * 1  2/6312 (0.03%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Bradyarrhythmia * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Cardiac arrest * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Cardiac failure congestive * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Haemorrhage coronary artery * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Myocarditis * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Right ventricular dysfunction * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Cardiac failure * 1  0/6312 (0.00%)  2/6254 (0.03%)  0/6267 (0.00%)  0/6253 (0.00%) 
Cardiopulmonary failure * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Coronary artery thrombosis * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Myocardial infarction * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Pericardial effusion * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Cardio-respiratory arrest * 1  2/6312 (0.03%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Dressler's syndrome * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Left ventricular failure * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Palpitations * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Congenital, familial and genetic disorders         
Ventricular septal defect * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Gastrointestinal angiodysplasia haemorrhagic * 1  0/6312 (0.00%)  1/6254 (0.02%)  1/6267 (0.02%)  0/6253 (0.00%) 
Atrial septal defect * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Phimosis * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Ear and labyrinth disorders         
Vertigo * 1  1/6312 (0.02%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Deafness * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Hypoacusis * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Endocrine disorders         
Pituitary cyst * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Eye disorders         
Diplopia * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Retinal detachment * 1  1/6312 (0.02%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Glaucoma * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Gastrointestinal disorders         
Gastrointestinal haemorrhage * 1  13/6312 (0.21%)  12/6254 (0.19%)  15/6267 (0.24%)  15/6253 (0.24%) 
Retroperitoneal haemorrhage * 1  2/6312 (0.03%)  4/6254 (0.06%)  9/6267 (0.14%)  8/6253 (0.13%) 
Upper gastrointestinal haemorrhage * 1  3/6312 (0.05%)  6/6254 (0.10%)  3/6267 (0.05%)  6/6253 (0.10%) 
Gastritis * 1  2/6312 (0.03%)  3/6254 (0.05%)  2/6267 (0.03%)  3/6253 (0.05%) 
Gastrointestinal ulcer haemorrhage * 1  0/6312 (0.00%)  1/6254 (0.02%)  2/6267 (0.03%)  3/6253 (0.05%) 
Abdominal pain upper * 1  0/6312 (0.00%)  1/6254 (0.02%)  1/6267 (0.02%)  3/6253 (0.05%) 
Gastric haemorrhage * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  3/6253 (0.05%) 
Retroperitoneal haematoma * 1  1/6312 (0.02%)  1/6254 (0.02%)  2/6267 (0.03%)  2/6253 (0.03%) 
Duodenal ulcer haemorrhage * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  2/6253 (0.03%) 
Peptic ulcer * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  2/6253 (0.03%) 
Constipation * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  2/6253 (0.03%) 
Pancreatitis acute * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  2/6253 (0.03%) 
Colitis ischaemic * 1  0/6312 (0.00%)  1/6254 (0.02%)  1/6267 (0.02%)  1/6253 (0.02%) 
Duodenal ulcer * 1  0/6312 (0.00%)  1/6254 (0.02%)  1/6267 (0.02%)  1/6253 (0.02%) 
Diarrhoea * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  1/6253 (0.02%) 
Gastritis haemorrhagic * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  1/6253 (0.02%) 
Oesophagitis haemorrhagic * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  1/6253 (0.02%) 
Abdominal discomfort * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Gastritis erosive * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Haematemesis * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Intestinal ischaemia * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Tongue haemorrhage * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Pancreatitis * 1  0/6312 (0.00%)  4/6254 (0.06%)  2/6267 (0.03%)  0/6253 (0.00%) 
Gastrooesophageal reflux disease * 1  0/6312 (0.00%)  3/6254 (0.05%)  2/6267 (0.03%)  0/6253 (0.00%) 
Haemorrhoidal haemorrhage * 1  0/6312 (0.00%)  2/6254 (0.03%)  1/6267 (0.02%)  0/6253 (0.00%) 
Gastric ulcer haemorrhage * 1  2/6312 (0.03%)  1/6254 (0.02%)  1/6267 (0.02%)  0/6253 (0.00%) 
Abdominal pain * 1  1/6312 (0.02%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Colonic pseudo-obstruction * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Gastric ulcer * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Gastrointestinal pain * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Ileus * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Lumbar hernia * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Nausea * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Rectal haemorrhage * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Small intestinal obstruction * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Vomiting * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Dysphagia * 1  1/6312 (0.02%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Diverticulum intestinal haemorrhagic * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Enterocolitis haemorrhagic * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Gastrointestinal ischaemia * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Haemorrhagic erosive gastritis * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Intestinal obstruction * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Peptic ulcer haemorrhage * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Periodontitis * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Peritonitis * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Acute abdomen * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Diverticular perforation * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Gastric polyps * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Hiatus hernia * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Large intestinal haemorrhage * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Melaena * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Mesenteric vein thrombosis * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Reflux oesophagitis * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
General disorders         
Puncture site haemorrhage * 1  17/6312 (0.27%)  21/6254 (0.34%)  22/6267 (0.35%)  31/6253 (0.50%) 
Pyrexia * 1  1/6312 (0.02%)  5/6254 (0.08%)  0/6267 (0.00%)  4/6253 (0.06%) 
Vessel puncture site haematoma * 1  2/6312 (0.03%)  2/6254 (0.03%)  1/6267 (0.02%)  2/6253 (0.03%) 
Chest pain * 1  2/6312 (0.03%)  3/6254 (0.05%)  5/6267 (0.08%)  1/6253 (0.02%) 
Multi-organ failure * 1  1/6312 (0.02%)  2/6254 (0.03%)  3/6267 (0.05%)  1/6253 (0.02%) 
Non-cardiac chest pain * 1  4/6312 (0.06%)  2/6254 (0.03%)  2/6267 (0.03%)  1/6253 (0.02%) 
Catheter site haematoma * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Implant site haemorrhage * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Inflammation * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Necrosis * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Systemic inflammatory response syndrome * 1  0/6312 (0.00%)  1/6254 (0.02%)  1/6267 (0.02%)  0/6253 (0.00%) 
Oedema peripheral * 1  1/6312 (0.02%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Application site erosion * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Catheter site haemorrhage * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Gait disturbance * 1  1/6312 (0.02%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Mechanical complication of implant * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Implant site haematoma * 1  2/6312 (0.03%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Fatigue * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Hepatobiliary disorders         
Cholecystitis acute * 1  3/6312 (0.05%)  4/6254 (0.06%)  1/6267 (0.02%)  2/6253 (0.03%) 
Cholelithiasis * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Bile duct obstruction * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Hepatitis * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Cholecystitis * 1  1/6312 (0.02%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Cholangitis * 1  2/6312 (0.03%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Hepatic failure * 1  2/6312 (0.03%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Acute hepatic failure * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Biliary colic * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Hyperbilirubinaemia * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Immune system disorders         
Hypersensitivity * 1  3/6312 (0.05%)  0/6254 (0.00%)  1/6267 (0.02%)  3/6253 (0.05%) 
Anaphylactic shock * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Anaphylactic reaction * 1  1/6312 (0.02%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Drug hypersensitivity * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Infections and infestations         
Pneumonia * 1  21/6312 (0.33%)  11/6254 (0.18%)  22/6267 (0.35%)  16/6253 (0.26%) 
Septic shock * 1  4/6312 (0.06%)  2/6254 (0.03%)  5/6267 (0.08%)  4/6253 (0.06%) 
Urinary tract infection * 1  3/6312 (0.05%)  0/6254 (0.00%)  3/6267 (0.05%)  3/6253 (0.05%) 
Postoperative wound infection * 1  3/6312 (0.05%)  3/6254 (0.05%)  2/6267 (0.03%)  3/6253 (0.05%) 
Bronchopneumonia * 1  0/6312 (0.00%)  0/6254 (0.00%)  2/6267 (0.03%)  2/6253 (0.03%) 
Bronchitis * 1  2/6312 (0.03%)  2/6254 (0.03%)  1/6267 (0.02%)  2/6253 (0.03%) 
Gastroenteritis * 1  4/6312 (0.06%)  1/6254 (0.02%)  1/6267 (0.02%)  2/6253 (0.03%) 
Lobar pneumonia * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  2/6253 (0.03%) 
Diverticulitis * 1  1/6312 (0.02%)  2/6254 (0.03%)  0/6267 (0.00%)  2/6253 (0.03%) 
Cellulitis * 1  1/6312 (0.02%)  0/6254 (0.00%)  2/6267 (0.03%)  1/6253 (0.02%) 
Lower respiratory tract infection * 1  3/6312 (0.05%)  1/6254 (0.02%)  1/6267 (0.02%)  1/6253 (0.02%) 
Lung infection * 1  2/6312 (0.03%)  1/6254 (0.02%)  1/6267 (0.02%)  1/6253 (0.02%) 
Pseudomembranous colitis * 1  0/6312 (0.00%)  1/6254 (0.02%)  1/6267 (0.02%)  1/6253 (0.02%) 
Post procedural infection * 1  1/6312 (0.02%)  0/6254 (0.00%)  1/6267 (0.02%)  1/6253 (0.02%) 
Post procedural sepsis * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  1/6253 (0.02%) 
Viral infection * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Bronchiolitis * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Catheter related infection * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Graft infection * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Infected skin ulcer * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Necrotising fasciitis * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Sepsis * 1  4/6312 (0.06%)  3/6254 (0.05%)  5/6267 (0.08%)  0/6253 (0.00%) 
Wound infection * 1  1/6312 (0.02%)  4/6254 (0.06%)  3/6267 (0.05%)  0/6253 (0.00%) 
Appendicitis * 1  0/6312 (0.00%)  2/6254 (0.03%)  1/6267 (0.02%)  0/6253 (0.00%) 
Bacteraemia * 1  1/6312 (0.02%)  1/6254 (0.02%)  1/6267 (0.02%)  0/6253 (0.00%) 
Endocarditis * 1  1/6312 (0.02%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Application site infection * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Gallbladder empyema * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Gastrointestinal infection * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Haematoma infection * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Influenza * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Pulmonary sepsis * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Sinusitis * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Mediastinitis * 1  0/6312 (0.00%)  3/6254 (0.05%)  0/6267 (0.00%)  0/6253 (0.00%) 
Dengue fever * 1  0/6312 (0.00%)  2/6254 (0.03%)  0/6267 (0.00%)  0/6253 (0.00%) 
Osteomyelitis * 1  1/6312 (0.02%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Pyelonephritis * 1  1/6312 (0.02%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Upper respiratory tract infection * 1  1/6312 (0.02%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Catheter sepsis * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Erysipelas * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Gangrene * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Meningitis coxsackie viral * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Pneumonia primary atypical * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Post procedural pneumonia * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Pyelonephritis acute * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Respiratory tract infection * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Endocarditis bacterial * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Escherichia sepsis * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Incision site infection * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Liver abscess * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Lower respiratory tract infection viral * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Myocarditis infectious * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Peridiverticulitis * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Peritoneal infection * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Puncture site infection * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Staphylococcal mediastinitis * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Urosepsis * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Injury, poisoning and procedural complications         
Operative haemorrhage * 1  39/6312 (0.62%)  50/6254 (0.80%)  57/6267 (0.91%)  48/6253 (0.77%) 
Vascular pseudoaneurysm * 1  7/6312 (0.11%)  8/6254 (0.13%)  7/6267 (0.11%)  9/6253 (0.14%) 
Post procedural haemorrhage * 1  12/6312 (0.19%)  16/6254 (0.26%)  18/6267 (0.29%)  6/6253 (0.10%) 
Wound dehiscence * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  2/6253 (0.03%) 
Fall * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Compression fracture * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Confusion postoperative * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Deep vein thrombosis postoperative * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Fat embolism * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Lower limb fracture * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Overdose * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Subcutaneous haematoma * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Incision site haemorrhage * 1  1/6312 (0.02%)  0/6254 (0.00%)  2/6267 (0.03%)  0/6253 (0.00%) 
Collapse of lung * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Femur fracture * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Haematuria traumatic * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Haemolytic transfusion reaction * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Hepatic haematoma * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Post procedural haematoma * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Postoperative fever * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Rib fracture * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Tibia fracture * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Vascular pseudoaneurysm ruptured * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Agitation postoperative * 1  0/6312 (0.00%)  2/6254 (0.03%)  0/6267 (0.00%)  0/6253 (0.00%) 
Postpericardiotomy syndrome * 1  0/6312 (0.00%)  2/6254 (0.03%)  0/6267 (0.00%)  0/6253 (0.00%) 
Subdural haematoma * 1  1/6312 (0.02%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Traumatic haemorrhage * 1  1/6312 (0.02%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Anaesthetic complication pulmonary * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Cardiac procedure complication * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Complication of device removal * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Facial bones fracture * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Incisional hernia, obstructive * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Joint dislocation * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Wound * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Anaemia postoperative * 1  2/6312 (0.03%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Chest injury * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Hip fracture * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Mechanical ventilation complication * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Procedural hypotension * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Subdural haemorrhage * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Investigations         
Haemoglobin decreased * 1  1/6312 (0.02%)  0/6254 (0.00%)  5/6267 (0.08%)  2/6253 (0.03%) 
Blood creatinine increased * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  1/6253 (0.02%) 
Platelet count decreased * 1  1/6312 (0.02%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Hepatic enzyme increased * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Metabolism and nutrition disorders         
Dehydration * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  3/6253 (0.05%) 
Gout * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  1/6253 (0.02%) 
Hypoglycaemia * 1  4/6312 (0.06%)  2/6254 (0.03%)  0/6267 (0.00%)  1/6253 (0.02%) 
Hyperkalaemia * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  1/6253 (0.02%) 
Diabetes mellitus * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Hydraemia * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Hyponatraemia * 1  1/6312 (0.02%)  0/6254 (0.00%)  2/6267 (0.03%)  0/6253 (0.00%) 
Hyperglycaemia * 1  0/6312 (0.00%)  0/6254 (0.00%)  2/6267 (0.03%)  0/6253 (0.00%) 
Diabetes mellitus inadequate control * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Fluid retention * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Hypocalcaemia * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Fluid overload * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Musculoskeletal and connective tissue disorders         
Compartment syndrome * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  1/6253 (0.02%) 
Musculoskeletal chest pain * 1  2/6312 (0.03%)  1/6254 (0.02%)  0/6267 (0.00%)  1/6253 (0.02%) 
Myalgia * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  1/6253 (0.02%) 
Osteoarthritis * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Gouty tophus * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Musculoskeletal pain * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Gouty arthritis * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Intervertebral disc protrusion * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Muscle haemorrhage * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Muscular weakness * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Osteochondrosis * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Acute leukaemia * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  1/6253 (0.02%) 
Lung neoplasm malignant * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  1/6253 (0.02%) 
Benign hepatic neoplasm * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Pituitary tumour benign * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Bronchial carcinoma * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Colon cancer * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Lung adenocarcinoma metastatic * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Metastases to lung * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Pancreatic carcinoma * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Rectosigmoid cancer * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Laryngeal cancer * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Lung adenocarcinoma * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Tumour associated fever * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Breast cancer * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Gastric cancer * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Metastatic carcinoma of the bladder * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Metastatic gastric cancer * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Nervous system disorders         
Haemorrhage intracranial * 1  1/6312 (0.02%)  1/6254 (0.02%)  1/6267 (0.02%)  2/6253 (0.03%) 
Haemorrhagic stroke * 1  1/6312 (0.02%)  3/6254 (0.05%)  2/6267 (0.03%)  1/6253 (0.02%) 
Transient ischaemic attack * 1  0/6312 (0.00%)  0/6254 (0.00%)  2/6267 (0.03%)  1/6253 (0.02%) 
Grand mal convulsion * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Critical illness polyneuropathy * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Optic neuritis * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Spinal cord ischaemia * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Syncope * 1  2/6312 (0.03%)  0/6254 (0.00%)  2/6267 (0.03%)  0/6253 (0.00%) 
Presyncope * 1  1/6312 (0.02%)  1/6254 (0.02%)  1/6267 (0.02%)  0/6253 (0.00%) 
Convulsion * 1  1/6312 (0.02%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Dizziness * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Drop attacks * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Encephalomalacia * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Loss of consciousness * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Paraesthesia * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Brain stem syndrome * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Carotid artery stenosis * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Dysarthria * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Headache * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Hypertensive encephalopathy * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Migraine without aura * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Multiple sclerosis * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Anoxic encephalopathy * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Neurological symptom * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Spinal cord infarction * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Psychiatric disorders         
Depression * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Major depression * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Psychotic disorder * 1  1/6312 (0.02%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Confusional state * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Delirium * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Anxiety * 1  1/6312 (0.02%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Completed suicide * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Generalised anxiety disorder * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Mental status changes * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Post-traumatic stress disorder * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Alcohol withdrawal syndrome * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Bipolar i disorder * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Mental disorder due to a general medical condition * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Suicide attempt * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Renal and urinary disorders         
Renal failure acute * 1  11/6312 (0.17%)  9/6254 (0.14%)  18/6267 (0.29%)  10/6253 (0.16%) 
Renal failure * 1  7/6312 (0.11%)  7/6254 (0.11%)  8/6267 (0.13%)  8/6253 (0.13%) 
Haematuria * 1  5/6312 (0.08%)  4/6254 (0.06%)  4/6267 (0.06%)  5/6253 (0.08%) 
Renal failure chronic * 1  2/6312 (0.03%)  2/6254 (0.03%)  0/6267 (0.00%)  3/6253 (0.05%) 
Calculus ureteric * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  2/6253 (0.03%) 
Cystitis haemorrhagic * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  1/6253 (0.02%) 
Renal colic * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Nephropathy toxic * 1  2/6312 (0.03%)  2/6254 (0.03%)  2/6267 (0.03%)  0/6253 (0.00%) 
Nephrolithiasis * 1  1/6312 (0.02%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Renal impairment * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Hydronephrosis * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Renal cyst * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Nephropathy * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Urethral stenosis * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Reproductive system and breast disorders         
Menorrhagia * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Ovarian haemorrhage * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Prostatitis * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Respiratory, thoracic and mediastinal disorders         
Pulmonary embolism * 1  5/6312 (0.08%)  7/6254 (0.11%)  5/6267 (0.08%)  10/6253 (0.16%) 
Atelectasis * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  3/6253 (0.05%) 
Chronic obstructive pulmonary disease * 1  2/6312 (0.03%)  4/6254 (0.06%)  5/6267 (0.08%)  2/6253 (0.03%) 
Respiratory failure * 1  3/6312 (0.05%)  4/6254 (0.06%)  4/6267 (0.06%)  2/6253 (0.03%) 
Pneumothorax * 1  5/6312 (0.08%)  1/6254 (0.02%)  2/6267 (0.03%)  2/6253 (0.03%) 
Epistaxis * 1  0/6312 (0.00%)  1/6254 (0.02%)  1/6267 (0.02%)  2/6253 (0.03%) 
Haemothorax * 1  0/6312 (0.00%)  1/6254 (0.02%)  1/6267 (0.02%)  2/6253 (0.03%) 
Respiratory arrest * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  2/6253 (0.03%) 
Pleural effusion * 1  3/6312 (0.05%)  0/6254 (0.00%)  3/6267 (0.05%)  1/6253 (0.02%) 
Acute respiratory distress syndrome * 1  2/6312 (0.03%)  0/6254 (0.00%)  1/6267 (0.02%)  1/6253 (0.02%) 
Pneumonitis * 1  1/6312 (0.02%)  0/6254 (0.00%)  1/6267 (0.02%)  1/6253 (0.02%) 
Pneumonia aspiration * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  1/6253 (0.02%) 
Pulmonary congestion * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  1/6253 (0.02%) 
Pulmonary oedema * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  1/6253 (0.02%) 
Haemoptysis * 1  1/6312 (0.02%)  2/6254 (0.03%)  0/6267 (0.00%)  1/6253 (0.02%) 
Respiratory distress * 1  1/6312 (0.02%)  1/6254 (0.02%)  0/6267 (0.00%)  1/6253 (0.02%) 
Thoracic haemorrhage * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Apnoea * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Lung disorder * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Respiratory depression * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Sleep apnoea syndrome * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Acute respiratory failure * 1  1/6312 (0.02%)  2/6254 (0.03%)  2/6267 (0.03%)  0/6253 (0.00%) 
Pleural haemorrhage * 1  1/6312 (0.02%)  1/6254 (0.02%)  2/6267 (0.03%)  0/6253 (0.00%) 
Cough * 1  0/6312 (0.00%)  1/6254 (0.02%)  1/6267 (0.02%)  0/6253 (0.00%) 
Hypoxia * 1  0/6312 (0.00%)  1/6254 (0.02%)  1/6267 (0.02%)  0/6253 (0.00%) 
Pulmonary alveolar haemorrhage * 1  1/6312 (0.02%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Acute pulmonary oedema * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Pleurisy * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Emphysema * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Idiopathic pulmonary fibrosis * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Laryngospasm * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Upper respiratory tract congestion * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Dyspnoea * 1  2/6312 (0.03%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Skin and subcutaneous tissue disorders         
Rash * 1  2/6312 (0.03%)  0/6254 (0.00%)  0/6267 (0.00%)  3/6253 (0.05%) 
Dermatitis allergic * 1  1/6312 (0.02%)  1/6254 (0.02%)  1/6267 (0.02%)  1/6253 (0.02%) 
Haemorrhage subcutaneous * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Palmar-plantar erythrodysaesthesia syndrome * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Rash maculo-papular * 1  0/6312 (0.00%)  0/6254 (0.00%)  2/6267 (0.03%)  0/6253 (0.00%) 
Angioedema * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Drug eruption * 1  1/6312 (0.02%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Urticaria * 1  1/6312 (0.02%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Erythema * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Henoch-schonlein purpura * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Skin haemorrhage * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Vascular disorders         
Deep vein thrombosis * 1  3/6312 (0.05%)  1/6254 (0.02%)  6/6267 (0.10%)  7/6253 (0.11%) 
Haemorrhage * 1  3/6312 (0.05%)  5/6254 (0.08%)  5/6267 (0.08%)  2/6253 (0.03%) 
Hypotension * 1  3/6312 (0.05%)  0/6254 (0.00%)  2/6267 (0.03%)  1/6253 (0.02%) 
Hypertension * 1  1/6312 (0.02%)  0/6254 (0.00%)  2/6267 (0.03%)  1/6253 (0.02%) 
Peripheral ischaemia * 1  0/6312 (0.00%)  1/6254 (0.02%)  1/6267 (0.02%)  1/6253 (0.02%) 
Hypertensive crisis * 1  1/6312 (0.02%)  0/6254 (0.00%)  1/6267 (0.02%)  1/6253 (0.02%) 
Arterial thrombosis limb * 1  0/6312 (0.00%)  2/6254 (0.03%)  0/6267 (0.00%)  1/6253 (0.02%) 
Haematoma * 1  1/6312 (0.02%)  1/6254 (0.02%)  0/6267 (0.00%)  1/6253 (0.02%) 
Aortic aneurysm rupture * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  1/6253 (0.02%) 
Shock * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Thrombosis * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Vena cava thrombosis * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Venous thrombosis limb * 1  0/6312 (0.00%)  0/6254 (0.00%)  0/6267 (0.00%)  1/6253 (0.02%) 
Peripheral embolism * 1  0/6312 (0.00%)  0/6254 (0.00%)  2/6267 (0.03%)  0/6253 (0.00%) 
Peripheral vascular disorder * 1  0/6312 (0.00%)  0/6254 (0.00%)  2/6267 (0.03%)  0/6253 (0.00%) 
Arteriovenous fistula * 1  0/6312 (0.00%)  3/6254 (0.05%)  1/6267 (0.02%)  0/6253 (0.00%) 
Aortic dissection * 1  2/6312 (0.03%)  1/6254 (0.02%)  1/6267 (0.02%)  0/6253 (0.00%) 
Femoral artery occlusion * 1  1/6312 (0.02%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Peripheral arterial occlusive disease * 1  1/6312 (0.02%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Arterial occlusive disease * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Iliac artery occlusion * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Orthostatic hypotension * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Phlebitis * 1  0/6312 (0.00%)  0/6254 (0.00%)  1/6267 (0.02%)  0/6253 (0.00%) 
Artery dissection * 1  1/6312 (0.02%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Arterial haemorrhage * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Arterial rupture * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Shock haemorrhagic * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Venous thrombosis * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Wound haemorrhage * 1  0/6312 (0.00%)  1/6254 (0.02%)  0/6267 (0.00%)  0/6253 (0.00%) 
Femoral artery dissection * 1  2/6312 (0.03%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
Venous haemorrhage * 1  1/6312 (0.02%)  0/6254 (0.00%)  0/6267 (0.00%)  0/6253 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Clopidogrel 300/75/75 mg + ASA Low Dose Clopidogrel 300/75/75 mg + ASA High Dose Clopidogrel 600/150/75 mg + ASA Low Dose Clopidogrel 600/150/75 mg + ASA High Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6312 (0.00%)   0/6254 (0.00%)   0/6267 (0.00%)   0/6253 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Publication of the study is made jointly in the name of all wholehearted collaborators. Other papers are authored based on the contributions of the individuals to the overall study. Sub-studies with scientific merit which have received prior approvals of the Steering Committee may be published separately in the names of contributing Investigators. A copy of all manuscripts are provided to the Sponsors for their review and the final decision to publish is made by the Steering Committee.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Trial Information Transparency Team
Organization: sanofi-aventis
EMail: GV-Contact-us@sanofi-aventis.com
Layout table for additonal information
Responsible Party: ICD, sanofi-aventis
ClinicalTrials.gov Identifier: NCT00335452     History of Changes
Other Study ID Numbers: EFC5965
EUDRACT: 2006-000313-38
First Submitted: June 8, 2006
First Posted: June 9, 2006
Results First Submitted: September 15, 2010
Results First Posted: October 7, 2010
Last Update Posted: November 18, 2010