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Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease (COMPASS)

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ClinicalTrials.gov Identifier: NCT01776424
Recruitment Status : Active, not recruiting
First Posted : January 28, 2013
Results First Posted : October 5, 2018
Last Update Posted : November 12, 2018
Sponsor:
Collaborators:
Population Health Research Institute
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Prevention & Control
Interventions Drug: Rivaroxaban (Xarelto, BAY59-7939)
Drug: Aspirin
Drug: Aspirin placebo
Drug: Rivaroxaban placebo
Drug: Pantoprazole
Enrollment 27395

Recruitment Details Study was conducted at 602 centers with randomized participants in 33 countries between 28 Feb 2013 (first patient first visit) and 18 Jul 2017 (last patient last visit for antithrombotic part).
Pre-assignment Details Overall, 29872 participants were screened, of which 2477 participants were screen failures. A total of 27395 participants were randomized to one of the study treatment arms.
Arm/Group Title Rivaroxaban 2.5mg + Aspirin 100mg Rivaroxaban 5mg + Aspirin Placebo Rivaroxaban Placebo + Aspirin 100mg
Hide Arm/Group Description Participants received Rivaroxaban 2.5 mg twice daily (bid) and Aspirin 100 mg once daily (od). All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a proton pump inhibitor (PPI), were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. Participants received Rivaroxaban 5 mg bid and Aspirin placebo od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. Participants received Rivaroxaban placebo bid and Aspirin 100 mg od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing.
Period Title: Overall Study
Started [1] 9152 9117 9126
Treated 9134 9110 9107
Completed 9132 9098 9102
Not Completed 20 19 24
Reason Not Completed
Lost to Follow-up             10             8             9
Withdrawal by Subject             10             11             15
[1]
Intention-to-treat (ITT) analysis set
Arm/Group Title Rivaroxaban 2.5mg + Aspirin 100mg Rivaroxaban 5mg + Aspirin Placebo Rivaroxaban Placebo + Aspirin 100mg Total
Hide Arm/Group Description Participants received Rivaroxaban 2.5 mg twice daily (bid) and Aspirin 100 mg once daily (od). All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a proton pump inhibitor (PPI), were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. Participants received Rivaroxaban 5 mg bid and Aspirin placebo od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. Participants received Rivaroxaban placebo bid and Aspirin 100 mg od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. Total of all reporting groups
Overall Number of Baseline Participants 9152 9117 9126 27395
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9152 participants 9117 participants 9126 participants 27395 participants
68.3  (7.9) 68.2  (7.9) 68.2  (8.0) 68.2  (7.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9152 participants 9117 participants 9126 participants 27395 participants
Female
2059
  22.5%
1972
  21.6%
1989
  21.8%
6020
  22.0%
Male
7093
  77.5%
7145
  78.4%
7137
  78.2%
21375
  78.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9152 participants 9117 participants 9126 participants 27395 participants
Chinese
388
   4.2%
381
   4.2%
376
   4.1%
1145
   4.2%
Hispanic
1769
  19.3%
1751
  19.2%
1758
  19.3%
5278
  19.3%
White/Caucasian
5673
  62.0%
5672
  62.2%
5682
  62.3%
17027
  62.2%
South Asian
107
   1.2%
102
   1.1%
106
   1.2%
315
   1.1%
Other Asian
956
  10.4%
938
  10.3%
915
  10.0%
2809
  10.3%
Black/African American
76
   0.8%
94
   1.0%
92
   1.0%
262
   1.0%
Other
183
   2.0%
179
   2.0%
197
   2.2%
559
   2.0%
1.Primary Outcome
Title The First Occurrence of the Composite Primary Efficacy Outcome, Myocardial Infarction (MI), Stroke, or Cardiovascular (CV) Death
Hide Description Count of participants and time from randomization to the first occurrence of the composite primary efficacy outcome, MI, stroke, or CV death were evaluated. Hazard ratios were calculated and reported as statistical analysis.
Time Frame For each participant, the first occurrence of the composite primary efficacy outcome after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set included all randomized subjects
Arm/Group Title Rivaroxaban 2.5mg + Aspirin 100mg Rivaroxaban 5mg + Aspirin Placebo Rivaroxaban Placebo + Aspirin 100mg
Hide Arm/Group Description:
Participants received Rivaroxaban 2.5 mg twice daily (bid) and Aspirin 100 mg once daily (od). All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a proton pump inhibitor (PPI), were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing.
Participants received Rivaroxaban 5 mg bid and Aspirin placebo od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing.
Participants received Rivaroxaban placebo bid and Aspirin 100 mg od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing.
Overall Number of Participants Analyzed 9152 9117 9126
Measure Type: Count of Participants
Unit of Measure: Participants
379
   4.1%
448
   4.9%
496
   5.4%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 2.5mg + Aspirin 100mg, Rivaroxaban Placebo + Aspirin 100mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00004
Comments Independent DSMB recommended to stop rivaroxaban/aspirin arms on 06FEB2017. At first interim analysis(~50% events) the log-rank test statistic for one primary comparison had crossed the modified Haybittle-Peto boundary(z=4) consistently over 3 months
Method Log Rank
Comments Log-rank test (stratified by pantoprazole randomization)
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.66 to 0.86
Estimation Comments Stratified Cox proportional hazards model
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 5mg + Aspirin Placebo, Rivaroxaban Placebo + Aspirin 100mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.11490
Comments [Not Specified]
Method Log Rank
Comments Log-rank test (stratified by pantoprazole randomization)
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.79 to 1.03
Estimation Comments Stratified Cox proportional hazards model
2.Primary Outcome
Title The First Occurrence of the Primary Safety Outcome Major Bleeding Based on a Modification of the International Society on Thrombosis and Haemostasis (ISTH) Criteria
Hide Description

Modified ISTH major bleeding is defined as: i) Fatal bleeding, or ii) Symptomatic bleeding in a critical area or organ, such as intraarticular, intracranial, intramuscular with compartment syndrome, intraocular, intraspinal, liver, pancreas, pericardial, respiratory, retroperitoneal, adrenal gland or kidney; or bleeding into the surgical site requiring reoperation, or iii) Bleeding leading to hospitalization (major bleeding also includes presentation to an acute care facility with discharge on the same day).

Count of participants and time from randomization to the first occurrence of the primary safety outcome major bleeding were evaluated. Hazard ratios were calculated and reported as statistical analysis.

Time Frame For each participant, the first occurrence of modified ISTH major bleeding after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set included all randomized subjects
Arm/Group Title Rivaroxaban 2.5mg + Aspirin 100mg Rivaroxaban 5mg + Aspirin Placebo Rivaroxaban Placebo + Aspirin 100mg
Hide Arm/Group Description:
Participants received Rivaroxaban 2.5 mg twice daily (bid) and Aspirin 100 mg once daily (od). All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a proton pump inhibitor (PPI), were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing.
Participants received Rivaroxaban 5 mg bid and Aspirin placebo od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing.
Participants received Rivaroxaban placebo bid and Aspirin 100 mg od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing.
Overall Number of Participants Analyzed 9152 9117 9126
Measure Type: Count of Participants
Unit of Measure: Participants
288
   3.1%
255
   2.8%
170
   1.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 2.5mg + Aspirin 100mg, Rivaroxaban Placebo + Aspirin 100mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments [Not Specified]
Method Log Rank
Comments Log-rank test (stratified by pantoprazole randomization)
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.70
Confidence Interval (2-Sided) 95%
1.40 to 2.05
Estimation Comments Stratified Cox proportional hazards model
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 5mg + Aspirin Placebo, Rivaroxaban Placebo + Aspirin 100mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00003
Comments [Not Specified]
Method Log Rank
Comments Log-rank test (stratified by pantoprazole randomization)
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.51
Confidence Interval (2-Sided) 95%
1.25 to 1.84
Estimation Comments Stratified Cox proportional hazards model
3.Secondary Outcome
Title The First Occurrence of Myocardial Infarction (MI), Ischemic Stroke, Acute Limb Ischemia (ALI), or Coronary Heart Disease (CHD) Death
Hide Description Count of participants and time from randomization to the first occurrence of MI, ischemic stroke, ALI, or CHD death were evaluated. Hazard ratios were calculated and reported as statistical analysis.
Time Frame For each participant, the first occurrence of MI, ALI, or CHD death after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set included all randomized subjects
Arm/Group Title Rivaroxaban 2.5mg + Aspirin 100mg Rivaroxaban 5mg + Aspirin Placebo Rivaroxaban Placebo + Aspirin 100mg
Hide Arm/Group Description:
Participants received Rivaroxaban 2.5 mg twice daily (bid) and Aspirin 100 mg once daily (od). All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a proton pump inhibitor (PPI), were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing.
Participants received Rivaroxaban 5 mg bid and Aspirin placebo od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing.
Participants received Rivaroxaban placebo bid and Aspirin 100 mg od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing.
Overall Number of Participants Analyzed 9152 9117 9126
Measure Type: Count of Participants
Unit of Measure: Participants
329
   3.6%
397
   4.4%
450
   4.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 2.5mg + Aspirin 100mg, Rivaroxaban Placebo + Aspirin 100mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00001
Comments Nominal p-value
Method Log Rank
Comments Log-rank test (stratified by pantoprazole randomization)
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.63 to 0.83
Estimation Comments Stratified Cox proportional hazards model
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 5mg + Aspirin Placebo, Rivaroxaban Placebo + Aspirin 100mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.06437
Comments Nominal p-value
Method Log Rank
Comments Log-rank test (stratified by pantoprazole randomization)
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.77 to 1.01
Estimation Comments Stratified Cox proportional hazards model
4.Secondary Outcome
Title The First Occurrence of MI, Ischemic Stroke, ALI, or Cardiovascular (CV) Death
Hide Description Count of participants and time from randomization to the first occurrence of MI, ischemic stroke, ALI, or CV death were evaluated. Hazard ratios were calculated and reported as statistical analysis.
Time Frame For each participant, the first occurrence of MI, ischemic stroke, ALI, or CV death after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set included all randomized subjects
Arm/Group Title Rivaroxaban 2.5mg + Aspirin 100mg Rivaroxaban 5mg + Aspirin Placebo Rivaroxaban Placebo + Aspirin 100mg
Hide Arm/Group Description:
Participants received Rivaroxaban 2.5 mg twice daily (bid) and Aspirin 100 mg once daily (od). All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a proton pump inhibitor (PPI), were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing.
Participants received Rivaroxaban 5 mg bid and Aspirin placebo od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing.
Participants received Rivaroxaban placebo bid and Aspirin 100 mg od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing.
Overall Number of Participants Analyzed 9152 9117 9126
Measure Type: Count of Participants
Unit of Measure: Participants
389
   4.3%
453
   5.0%
516
   5.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 2.5mg + Aspirin 100mg, Rivaroxaban Placebo + Aspirin 100mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00001
Comments Nominal p-value
Method Log Rank
Comments Log-rank test (stratified by pantoprazole randomization)
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.65 to 0.85
Estimation Comments Stratified Cox proportional hazards model
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 5mg + Aspirin Placebo, Rivaroxaban Placebo + Aspirin 100mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03995
Comments Nominal p-value
Method Log Rank
Comments Log-rank test (stratified by pantoprazole randomization)
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.88
Confidence Interval 95%
0.77 to 0.99
Estimation Comments Stratified Cox proportional hazards model
5.Secondary Outcome
Title All-cause Mortality
Hide Description Count of participants and time from randomization to death by all cause were evaluated. Hazard ratios were calculated and reported as statistical analysis.
Time Frame For each participants, death by any cause after randomization up until the global rivaroxaban/aspirin outcomes cut-off date (06 FEB 2017) was considered. The mean time in follow-up until that date was 702 days.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set included all randomized subjects
Arm/Group Title Rivaroxaban 2.5mg + Aspirin 100mg Rivaroxaban 5mg + Aspirin Placebo Rivaroxaban Placebo + Aspirin 100mg
Hide Arm/Group Description:
Participants received Rivaroxaban 2.5 mg twice daily (bid) and Aspirin 100 mg once daily (od). All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a proton pump inhibitor (PPI), were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing.
Participants received Rivaroxaban 5 mg bid and Aspirin placebo od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing.
Participants received Rivaroxaban placebo bid and Aspirin 100 mg od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing.
Overall Number of Participants Analyzed 9152 9117 9126
Measure Type: Count of Participants
Unit of Measure: Participants
313
   3.4%
366
   4.0%
378
   4.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 2.5mg + Aspirin 100mg, Rivaroxaban Placebo + Aspirin 100mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01062
Comments Nominal p-value
Method Log Rank
Comments Log-rank test (stratified by pantoprazole randomization)
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.71 to 0.96
Estimation Comments Stratified Cox proportional hazards model
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rivaroxaban 5mg + Aspirin Placebo, Rivaroxaban Placebo + Aspirin 100mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.66418
Comments Nominal p-value
Method Log Rank
Comments Log-rank test (stratified by pantoprazole randomization)
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.84 to 1.12
Estimation Comments Stratified Cox proportional hazards model
Time Frame From randomization up until 2 days following permanent discontinuation of any antithrombotic study treatment
Adverse Event Reporting Description All-Cause Mortality reporting in the adverse event (AE) section encompasses all death cases in the safety analysis set before database closure in July 2017. Analysis of serious AEs in the specified time frame encompasses all subjects in the safety analysis set.
 
Arm/Group Title Rivaroxaban 2.5mg + Aspirin 100mg Rivaroxaban 5mg + Aspirin Placebo Rivaroxaban Placebo + Aspirin 100mg
Hide Arm/Group Description Participants received Rivaroxaban 2.5 mg twice daily (bid) and Aspirin 100 mg once daily (od). All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a proton pump inhibitor (PPI), were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. Participants received Rivaroxaban 5 mg bid and Aspirin placebo od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing. Participants received Rivaroxaban placebo bid and Aspirin 100 mg od. All doses were provided in tablet form for oral administration. Participants who did not have a continuous need to take a PPI, were randomized 1:1 to receive pantoprazole 40 mg (tablet form for oral administration, od) or matching placebo od. The pantoprazole/placebo part of the study is ongoing.
All-Cause Mortality
Rivaroxaban 2.5mg + Aspirin 100mg Rivaroxaban 5mg + Aspirin Placebo Rivaroxaban Placebo + Aspirin 100mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   376/9134 (4.12%)      422/9110 (4.63%)      442/9107 (4.85%)    
Show Serious Adverse Events Hide Serious Adverse Events
Rivaroxaban 2.5mg + Aspirin 100mg Rivaroxaban 5mg + Aspirin Placebo Rivaroxaban Placebo + Aspirin 100mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   641/9134 (7.02%)      624/9110 (6.85%)      582/9107 (6.39%)    
Blood and lymphatic system disorders       
Anaemia * 1  13/9134 (0.14%)  14 10/9110 (0.11%)  11 2/9107 (0.02%)  2
Febrile neutropenia * 1  0/9134 (0.00%)  0 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Haemolytic anaemia * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Hypochromic anaemia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Iron deficiency anaemia * 1  3/9134 (0.03%)  3 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Leukopenia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Microcytic anaemia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Normochromic normocytic anaemia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Pancytopenia * 1  3/9134 (0.03%)  3 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Pernicious anaemia * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Thrombocytopenia * 1  5/9134 (0.05%)  5 0/9110 (0.00%)  0 2/9107 (0.02%)  2
Hypereosinophilic syndrome * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Haemorrhagic diathesis * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Immune thrombocytopenic purpura * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Cardiac disorders       
Acute myocardial infarction * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Angina pectoris * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 3/9107 (0.03%)  3
Arrhythmia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Atrial fibrillation * 1  4/9134 (0.04%)  4 5/9110 (0.05%)  5 10/9107 (0.11%)  10
Atrial flutter * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Atrioventricular block complete * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 3/9107 (0.03%)  3
Bradycardia * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Cardiac arrest * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Cardiac failure * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Cardiac failure chronic * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Cardiac failure congestive * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Cardio-respiratory arrest * 1  2/9134 (0.02%)  2 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Cor pulmonale * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Coronary artery disease * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Dressler's syndrome * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Myocardial ischaemia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Supraventricular tachycardia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Ventricular tachycardia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Cardiac ventricular thrombosis * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Coronary artery perforation * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Sinus node dysfunction * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Congenital, familial and genetic disorders       
Fabry's disease * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Hydrocele * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Ear and labyrinth disorders       
Vertigo * 1  2/9134 (0.02%)  2 5/9110 (0.05%)  5 6/9107 (0.07%)  6
Vertigo positional * 1  1/9134 (0.01%)  1 2/9110 (0.02%)  2 1/9107 (0.01%)  1
Vestibular disorder * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Hypoacusis * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Ear discomfort * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  3 0/9107 (0.00%)  0
Deafness bilateral * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Sudden hearing loss * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Endocrine disorders       
Adrenal insufficiency * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Basedow's disease * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 2/9107 (0.02%)  2
Hyperparathyroidism primary * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Hyperthyroidism * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Hypothyroidism * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Toxic nodular goitre * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Thyroid mass * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Eye disorders       
Amaurosis fugax * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Blindness transient * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Blindness unilateral * 1  0/9134 (0.00%)  0 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Cataract * 1  16/9134 (0.18%)  19 11/9110 (0.12%)  13 7/9107 (0.08%)  9
Cataract cortical * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Cataract nuclear * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  2
Diplopia * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Eyelid ptosis * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Glaucoma * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Macular oedema * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Optic ischaemic neuropathy * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Retinal artery occlusion * 1  2/9134 (0.02%)  2 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Retinal degeneration * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Retinal detachment * 1  3/9134 (0.03%)  3 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Retinal haemorrhage * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 2/9107 (0.02%)  2
Retinal vein thrombosis * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Sudden visual loss * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Vision blurred * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Visual acuity reduced * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Visual impairment * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 2/9107 (0.02%)  2
Vitreous haemorrhage * 1  2/9134 (0.02%)  3 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Macular hole * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Dacryostenosis acquired * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Entropion * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Retinal vascular thrombosis * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Age-related macular degeneration * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Macular fibrosis * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Gastrointestinal disorders       
Abdominal distension * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Abdominal pain * 1  3/9134 (0.03%)  3 4/9110 (0.04%)  4 5/9107 (0.05%)  5
Abdominal pain upper * 1  1/9134 (0.01%)  1 4/9110 (0.04%)  4 4/9107 (0.04%)  4
Acute abdomen * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Anal fistula * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Ascites * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  2 0/9107 (0.00%)  0
Barrett's oesophagus * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Chronic gastritis * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Colitis ischaemic * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Constipation * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Diaphragmatic hernia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Diarrhoea * 1  3/9134 (0.03%)  3 5/9110 (0.05%)  5 3/9107 (0.03%)  3
Diverticulum * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Diverticulum intestinal * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Diverticulum intestinal haemorrhagic * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Duodenal perforation * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Duodenal ulcer * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Duodenal ulcer haemorrhage * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Dyspepsia * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Enteritis * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Flatulence * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Food poisoning * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Gallstone ileus * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Gastric ulcer * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Gastric ulcer haemorrhage * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Gastritis * 1  6/9134 (0.07%)  7 2/9110 (0.02%)  2 4/9107 (0.04%)  4
Gastritis erosive * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Gastrooesophageal reflux disease * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Gastrointestinal disorder * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Gastrointestinal haemorrhage * 1  5/9134 (0.05%)  7 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Haemorrhoids * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Ileus * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 3/9107 (0.03%)  3
Ileus paralytic * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Incarcerated inguinal hernia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Inguinal hernia * 1  5/9134 (0.05%)  5 2/9110 (0.02%)  2 5/9107 (0.05%)  5
Intestinal ischaemia * 1  2/9134 (0.02%)  2 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Intestinal obstruction * 1  2/9134 (0.02%)  2 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Intestinal perforation * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Large intestine perforation * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Melaena * 1  4/9134 (0.04%)  4 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Oesophageal achalasia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Oesophageal stenosis * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Oesophagitis * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Pancreatitis * 1  5/9134 (0.05%)  5 10/9110 (0.11%)  11 8/9107 (0.09%)  9
Pancreatitis acute * 1  6/9134 (0.07%)  6 5/9110 (0.05%)  5 10/9107 (0.11%)  10
Pancreatitis chronic * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Pancreatitis haemorrhagic * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Peptic ulcer * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Peptic ulcer haemorrhage * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Small intestinal obstruction * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Spigelian hernia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Stomatitis * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Umbilical hernia * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Umbilical hernia, obstructive * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Volvulus * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Vomiting * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 2/9107 (0.02%)  2
Pancreatic mass * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Anal haemorrhage * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Subileus * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Lower gastrointestinal haemorrhage * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Dyschezia * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Gastric antral vascular ectasia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Large intestine polyp * 1  7/9134 (0.08%)  7 14/9110 (0.15%)  14 9/9107 (0.10%)  9
Oesophageal rupture * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Haemorrhoidal haemorrhage * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Faecaloma * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Alcoholic pancreatitis * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Gastrointestinal toxicity * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Gastric mucosal lesion * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Diverticular perforation * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Inguinal hernia strangulated * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Ischaemic enteritis * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Abdominal incarcerated hernia * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
General disorders       
Asthenia * 1  0/9134 (0.00%)  0 3/9110 (0.03%)  3 1/9107 (0.01%)  1
Chest discomfort * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Chest pain * 1  7/9134 (0.08%)  7 13/9110 (0.14%)  13 4/9107 (0.04%)  4
Death * 1  3/9134 (0.03%)  3 3/9110 (0.03%)  3 7/9107 (0.08%)  7
Face oedema * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Gait disturbance * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Generalised oedema * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Impaired healing * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Malaise * 1  0/9134 (0.00%)  0 3/9110 (0.03%)  3 0/9107 (0.00%)  0
Oedema peripheral * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Pain * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Pyrexia * 1  2/9134 (0.02%)  2 2/9110 (0.02%)  2 2/9107 (0.02%)  2
Sudden death * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Peripheral swelling * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Nodule * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Microlithiasis * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Unevaluable event * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Non-cardiac chest pain * 1  9/9134 (0.10%)  9 4/9110 (0.04%)  5 7/9107 (0.08%)  7
Accidental death * 1  0/9134 (0.00%)  0 3/9110 (0.03%)  3 0/9107 (0.00%)  0
Stent-graft endoleak * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Medical device site erosion * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Vascular stent stenosis * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Multiple organ dysfunction syndrome * 1  3/9134 (0.03%)  3 1/9110 (0.01%)  1 2/9107 (0.02%)  2
Hepatobiliary disorders       
Bile duct stone * 1  4/9134 (0.04%)  4 3/9110 (0.03%)  3 2/9107 (0.02%)  2
Biliary colic * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Cholangitis * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 3/9107 (0.03%)  3
Cholangitis acute * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 2/9107 (0.02%)  2
Cholecystitis * 1  8/9134 (0.09%)  8 9/9110 (0.10%)  9 10/9107 (0.11%)  10
Cholecystitis acute * 1  5/9134 (0.05%)  5 7/9110 (0.08%)  7 9/9107 (0.10%)  9
Cholecystitis chronic * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Cholelithiasis * 1  4/9134 (0.04%)  4 1/9110 (0.01%)  1 6/9107 (0.07%)  6
Cholestasis * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Cirrhosis alcoholic * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Hepatic failure * 1  1/9134 (0.01%)  1 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Hepatitis * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Jaundice * 1  2/9134 (0.02%)  2 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Jaundice cholestatic * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Liver disorder * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Bile duct stenosis * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Bile duct obstruction * 1  0/9134 (0.00%)  0 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Hepatic mass * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Drug-induced liver injury * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Immune system disorders       
Anaphylactic reaction * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Contrast media reaction * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Food allergy * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Hypersensitivity * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Infections and infestations       
Appendicitis * 1  3/9134 (0.03%)  3 6/9110 (0.07%)  6 0/9107 (0.00%)  0
Appendicitis perforated * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Bacteraemia * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 2/9107 (0.02%)  2
Brain abscess * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Bronchitis * 1  3/9134 (0.03%)  3 3/9110 (0.03%)  4 1/9107 (0.01%)  1
Cellulitis * 1  9/9134 (0.10%)  9 11/9110 (0.12%)  12 7/9107 (0.08%)  8
Clostridium difficile colitis * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Cytomegalovirus infection * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Dengue fever * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Dermatitis infected * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Diabetic gangrene * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Diarrhoea infectious * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Diverticulitis * 1  3/9134 (0.03%)  3 4/9110 (0.04%)  5 3/9107 (0.03%)  3
Diverticulitis intestinal haemorrhagic * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Encephalitis * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Encephalitis viral * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Erysipelas * 1  3/9134 (0.03%)  3 5/9110 (0.05%)  5 6/9107 (0.07%)  7
Gangrene * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Gastroenteritis * 1  5/9134 (0.05%)  5 3/9110 (0.03%)  3 4/9107 (0.04%)  4
Herpes zoster * 1  4/9134 (0.04%)  4 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Infected skin ulcer * 1  0/9134 (0.00%)  0 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Influenza * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 2/9107 (0.02%)  2
Laryngitis * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Liver abscess * 1  0/9134 (0.00%)  0 2/9110 (0.02%)  2 1/9107 (0.01%)  1
Localised infection * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Lower respiratory tract infection * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Mediastinitis * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Orchitis * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Osteomyelitis * 1  2/9134 (0.02%)  2 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Otitis media chronic * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Periodontitis * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Peritonitis * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Pharyngitis * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Pneumonia * 1  15/9134 (0.16%)  16 21/9110 (0.23%)  26 23/9107 (0.25%)  23
Pneumonia klebsiella * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Postoperative wound infection * 1  2/9134 (0.02%)  3 4/9110 (0.04%)  4 3/9107 (0.03%)  3
Pulmonary tuberculosis * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Pyelonephritis * 1  2/9134 (0.02%)  2 1/9110 (0.01%)  1 3/9107 (0.03%)  4
Pyelonephritis acute * 1  1/9134 (0.01%)  2 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Renal abscess * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Sepsis * 1  17/9134 (0.19%)  19 16/9110 (0.18%)  16 15/9107 (0.16%)  15
Septic shock * 1  3/9134 (0.03%)  3 7/9110 (0.08%)  7 7/9107 (0.08%)  7
Skin infection * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Subcutaneous abscess * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Superinfection * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Tooth abscess * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Tracheobronchitis * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Tuberculosis * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Upper respiratory tract infection * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Urinary tract infection * 1  15/9134 (0.16%)  16 13/9110 (0.14%)  14 7/9107 (0.08%)  7
Viral myocarditis * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Wound infection * 1  1/9134 (0.01%)  1 2/9110 (0.02%)  2 6/9107 (0.07%)  6
Urosepsis * 1  8/9134 (0.09%)  8 4/9110 (0.04%)  4 6/9107 (0.07%)  7
Anal abscess * 1  0/9134 (0.00%)  0 2/9110 (0.02%)  2 1/9107 (0.01%)  1
Rectal abscess * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Groin abscess * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Staphylococcal bacteraemia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Postoperative abscess * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Campylobacter infection * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Haematoma infection * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Pulmonary sepsis * 1  1/9134 (0.01%)  1 2/9110 (0.02%)  2 2/9107 (0.02%)  2
Neuroborreliosis * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Escherichia urinary tract infection * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Arthritis bacterial * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 2/9107 (0.02%)  2
Abscess neck * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Clostridium difficile infection * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Escherichia bacteraemia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Pneumonia necrotising * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Subdiaphragmatic abscess * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Staphylococcal sepsis * 1  0/9134 (0.00%)  0 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Infective exacerbation of chronic obstructive airways disease * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 2/9107 (0.02%)  2
Periorbital cellulitis * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Biliary sepsis * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Cerebral toxoplasmosis * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Staphylococcal infection * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Enteritis infectious * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Klebsiella bacteraemia * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Intervertebral discitis * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Diabetic foot infection * 1  1/9134 (0.01%)  1 3/9110 (0.03%)  4 2/9107 (0.02%)  2
Bacterial infection * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Arthritis infective * 1  0/9134 (0.00%)  0 3/9110 (0.03%)  3 0/9107 (0.00%)  0
Gastroenteritis bacterial * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Klebsiella infection * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Borrelia infection * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Atypical mycobacterial infection * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Biliary tract infection * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Peritonitis bacterial * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Mycobacterial infection * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Soft tissue infection * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 2/9107 (0.02%)  2
Cholecystitis infective * 1  1/9134 (0.01%)  1 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Device related infection * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Post procedural sepsis * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Post procedural infection * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Gastroenteritis norovirus * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Infectious pleural effusion * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Colonic abscess * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Cholangitis infective * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Varicella zoster virus infection * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Infected bite * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Bacterial abdominal infection * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Injury, poisoning and procedural complications       
Blindness traumatic * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Carbon monoxide poisoning * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Chemical poisoning * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Clavicle fracture * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Concussion * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Extradural haematoma * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Fall * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 2/9107 (0.02%)  2
Fat embolism * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Femoral neck fracture * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Femur fracture * 1  3/9134 (0.03%)  4 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Foreign body in eye * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Gun shot wound * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Hand fracture * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Head injury * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Hip fracture * 1  4/9134 (0.04%)  4 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Incisional hernia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Incisional hernia, obstructive * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Injury * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Ligament sprain * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Multiple injuries * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Overdose * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Poisoning deliberate * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Radius fracture * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Rib fracture * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Road traffic accident * 1  4/9134 (0.04%)  4 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Spinal compression fracture * 1  2/9134 (0.02%)  2 2/9110 (0.02%)  2 2/9107 (0.02%)  2
Spinal cord injury cervical * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Spinal fracture * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Subarachnoid haemorrhage * 1  2/9134 (0.02%)  2 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Subdural haematoma * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Tendon rupture * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Tibia fracture * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Ulna fracture * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Vascular injury * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Wound secretion * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Cervical vertebral fracture * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Muscle strain * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Contusion * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Post procedural haemorrhage * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Brain contusion * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 2/9107 (0.02%)  2
Thermal burn * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Wound necrosis * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Postoperative ileus * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Wound evisceration * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Postoperative renal failure * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Vascular procedure complication * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Pelvic fracture * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Limb injury * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Skull fracture * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Chest injury * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Bladder injury * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Vascular bypass dysfunction * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Limb crushing injury * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Post procedural swelling * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Craniocerebral injury * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Procedural intestinal perforation * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Traumatic haemothorax * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Investigations       
Amylase increased * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  2
Arteriogram coronary * 1  9/9134 (0.10%)  11 9/9110 (0.10%)  9 12/9107 (0.13%)  14
Aspartate aminotransferase increased * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Biopsy prostate * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Blood glucose increased * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Blood pressure increased * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Bronchoscopy * 1  1/9134 (0.01%)  2 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Catheterisation cardiac * 1  2/9134 (0.02%)  2 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Colonoscopy * 1  0/9134 (0.00%)  0 2/9110 (0.02%)  3 1/9107 (0.01%)  1
Haemoglobin decreased * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Lipase increased * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Liver function test abnormal * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Prostatic specific antigen increased * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Weight decreased * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Urological examination * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Computerised tomogram thorax * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Angiogram peripheral * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Anticoagulation drug level above therapeutic * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Hepatic enzyme increased * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 2/9107 (0.02%)  2
Blood electrolytes abnormal * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Investigation * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  2 1/9107 (0.01%)  1
Stenotrophomonas test positive * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Influenza A virus test positive * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Hepatitis B core antibody positive * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Metabolism and nutrition disorders       
Cachexia * 1  0/9134 (0.00%)  0 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Dehydration * 1  4/9134 (0.04%)  4 2/9110 (0.02%)  2 1/9107 (0.01%)  1
Diabetes mellitus * 1  4/9134 (0.04%)  5 5/9110 (0.05%)  5 6/9107 (0.07%)  6
Diabetes mellitus inadequate control * 1  1/9134 (0.01%)  1 3/9110 (0.03%)  4 4/9107 (0.04%)  4
Diabetic ketoacidosis * 1  1/9134 (0.01%)  1 2/9110 (0.02%)  2 1/9107 (0.01%)  1
Fluid overload * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Gout * 1  1/9134 (0.01%)  1 4/9110 (0.04%)  4 1/9107 (0.01%)  1
Hyperammonaemia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Hyperglycaemia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Hyperkalaemia * 1  2/9134 (0.02%)  2 2/9110 (0.02%)  3 1/9107 (0.01%)  1
Hypoglycaemia * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Hypokalaemia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Hypomagnesaemia * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Hyponatraemia * 1  0/9134 (0.00%)  0 3/9110 (0.03%)  3 2/9107 (0.02%)  2
Lactic acidosis * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Marasmus * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Hyperglycaemic hyperosmolar nonketotic syndrome * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Type 2 diabetes mellitus * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Diabetic metabolic decompensation * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  3/9134 (0.03%)  3 3/9110 (0.03%)  3 1/9107 (0.01%)  1
Arthritis * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 2/9107 (0.02%)  2
Arthropathy * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Back pain * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Bursitis * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Haemarthrosis * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Joint swelling * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Lumbar spinal stenosis * 1  3/9134 (0.03%)  3 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Muscle atrophy * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Musculoskeletal pain * 1  2/9134 (0.02%)  2 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Myalgia * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Myopathy * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Neck pain * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Osteitis * 1  3/9134 (0.03%)  3 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Osteoarthritis * 1  5/9134 (0.05%)  6 6/9110 (0.07%)  7 8/9107 (0.09%)  8
Pain in extremity * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 4/9107 (0.04%)  4
Polymyalgia rheumatica * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Rhabdomyolysis * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Rotator cuff syndrome * 1  0/9134 (0.00%)  0 4/9110 (0.04%)  4 1/9107 (0.01%)  1
Scoliosis * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Spinal column stenosis * 1  1/9134 (0.01%)  3 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Spinal osteoarthritis * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Synovial cyst * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Intervertebral disc protrusion * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Musculoskeletal chest pain * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Spondyloarthropathy * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Facet joint syndrome * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Seronegative arthritis * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Acute leukaemia * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Acute myeloid leukaemia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 2/9107 (0.02%)  2
Adenocarcinoma * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Adenocarcinoma gastric * 1  0/9134 (0.00%)  0 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Adenocarcinoma of colon * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Adenoma benign * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
B-cell lymphoma * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 2/9107 (0.02%)  2
Basal cell carcinoma * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Bile duct cancer * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Bladder cancer * 1  2/9134 (0.02%)  2 1/9110 (0.01%)  1 6/9107 (0.07%)  6
Bladder cancer recurrent * 1  0/9134 (0.00%)  0 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Bladder neoplasm * 1  0/9134 (0.00%)  0 2/9110 (0.02%)  2 1/9107 (0.01%)  1
Bone cancer * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Bowen's disease * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Breast cancer * 1  5/9134 (0.05%)  5 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Bronchial carcinoma * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Cervix carcinoma * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Cholangiocarcinoma * 1  0/9134 (0.00%)  0 2/9110 (0.02%)  2 1/9107 (0.01%)  1
Cholesteatoma * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 2/9107 (0.02%)  3
Colon cancer * 1  9/9134 (0.10%)  9 7/9110 (0.08%)  7 4/9107 (0.04%)  4
Colon cancer stage IV * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Fibroma * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Gastric cancer * 1  8/9134 (0.09%)  8 8/9110 (0.09%)  9 5/9107 (0.05%)  5
Gastrointestinal carcinoma * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Haemangioma of skin * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Hodgkin's disease * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Hypopharyngeal cancer * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Intracranial tumour haemorrhage * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Laryngeal neoplasm * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Leukaemia * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Lipoma * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Lung adenocarcinoma * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 2/9107 (0.02%)  2
Lung carcinoma cell type unspecified stage IV * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Lymphoma * 1  0/9134 (0.00%)  0 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Malignant neoplasm of renal pelvis * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Malignant neoplasm of spermatic cord * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Meningioma * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Meningioma benign * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Mesothelioma * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Mesothelioma malignant * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Metastases to bone * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Metastases to liver * 1  1/9134 (0.01%)  1 2/9110 (0.02%)  2 1/9107 (0.01%)  1
Metastases to lung * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Metastases to neck * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Metastatic malignant melanoma * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Myelodysplastic syndrome * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Neoplasm malignant * 1  0/9134 (0.00%)  0 5/9110 (0.05%)  5 7/9107 (0.08%)  7
Oesophageal carcinoma * 1  2/9134 (0.02%)  2 1/9110 (0.01%)  1 3/9107 (0.03%)  4
Pancreatic carcinoma * 1  4/9134 (0.04%)  4 5/9110 (0.05%)  5 1/9107 (0.01%)  1
Pancreatic carcinoma metastatic * 1  2/9134 (0.02%)  2 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Papillary thyroid cancer * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Plasma cell myeloma * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Prostate cancer metastatic * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Prostate cancer recurrent * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Prostate cancer stage IV * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Rectal adenocarcinoma * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Rectal cancer * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 2/9107 (0.02%)  2
Rectal cancer stage IV * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Renal cancer * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Retroperitoneal cancer * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Skin cancer * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Small cell lung cancer * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Small intestine carcinoma metastatic * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Squamous cell carcinoma of lung * 1  2/9134 (0.02%)  2 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Squamous cell carcinoma of the cervix * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Tongue neoplasm malignant stage unspecified * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Tonsil cancer * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Tracheal cancer * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Transitional cell carcinoma * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Uterine leiomyoma * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Colon adenoma * 1  3/9134 (0.03%)  3 2/9110 (0.02%)  2 0/9107 (0.00%)  0
Tumour haemorrhage * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Lung cancer metastatic * 1  2/9134 (0.02%)  2 1/9110 (0.01%)  1 2/9107 (0.02%)  2
Renal cancer metastatic * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Metastases to peritoneum * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Small intestine carcinoma * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Brain cancer metastatic * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Hepatic cancer metastatic * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Neuroendocrine carcinoma * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Cancer pain * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Lung neoplasm malignant * 1  17/9134 (0.19%)  18 13/9110 (0.14%)  13 11/9107 (0.12%)  12
Extradural neoplasm * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Prostate cancer * 1  12/9134 (0.13%)  12 10/9110 (0.11%)  10 4/9107 (0.04%)  4
Brain neoplasm * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 1/9107 (0.01%)  1
Nervous system neoplasm benign * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Metastatic neoplasm * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Colorectal cancer * 1  2/9134 (0.02%)  2 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Renal neoplasm * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 2/9107 (0.02%)  2
Malignant mesenchymoma * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Pituitary tumour benign * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Adrenal neoplasm * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Pancreatic neoplasm * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Lung neoplasm * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Splenic marginal zone lymphoma * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Tonsillar neoplasm * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Metastasis * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Gastrooesophageal cancer * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Colon cancer stage 0 * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Ameloblastoma * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Gallbladder cancer metastatic * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Renal cell carcinoma * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Intraductal papillary mucinous neoplasm * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Hepatic cancer * 1  2/9134 (0.02%)  2 2/9110 (0.02%)  2 3/9107 (0.03%)  3
Hepatocellular carcinoma * 1  4/9134 (0.04%)  4 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Central nervous system neuroblastoma * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Adrenal gland cancer * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Nervous system disorders       
Altered state of consciousness * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Amnesia * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Amyotrophic lateral sclerosis * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Carotid artery stenosis * 1  0/9134 (0.00%)  0 2/9110 (0.02%)  2 2/9107 (0.02%)  2
Carpal tunnel syndrome * 1  1/9134 (0.01%)  1 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Cerebral haemorrhage * 1  2/9134 (0.02%)  2 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Cerebral infarction * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Cerebral ischaemia * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Cerebral venous thrombosis * 1  0/9134 (0.00%)  0 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Cerebrospinal fluid leakage * 1  1/9134 (0.01%)  1 0/9110 (0.00%)  0 0/9107 (0.00%)  0
Cerebrovascular accident * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Cervicobrachial syndrome * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1
Dementia * 1  2/9134 (0.02%)  2 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Dementia Alzheimer's type * 1  2/9134 (0.02%)  2 1/9110 (0.01%)  1 0/9107 (0.00%)  0
Demyelination * 1  0/9134 (0.00%)  0 0/9110 (0.00%)  0 1/9107 (0.01%)  1