A Comparison of Prasugrel and Clopidogrel in Acute Coronary Syndrome Subjects (TRILOGY ACS)

This study has been completed.
Sponsor:
Collaborators:
Daiichi Sankyo Co., Ltd.
Duke Clinical Research Institute
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00699998
First received: June 16, 2008
Last updated: March 21, 2013
Last verified: March 2013
Results First Received: March 21, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Acute Coronary Syndrome
Interventions: Drug: Clopidogrel
Drug: Prasugrel
Drug: Commercially-available Aspirin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Prasugrel: <75 Years of Age

Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age.

Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study.

Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.

Prasugrel: 75 Years of Age or Older

Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older.

Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study.

Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.

Clopidogrel: <75 Years of Age

Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age.

Commercially-available Aspirin : Low-dose aspirin, oral, as prescribed by physician through end of study

Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study

Clopidogrel: 75 Years of Age or Older

Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older.

Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study.

Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.


Participant Flow:   Overall Study
    Prasugrel: <75 Years of Age     Prasugrel: 75 Years of Age or Older     Clopidogrel: <75 Years of Age     Clopidogrel: 75 Years of Age or Older  
STARTED     3620     1043     3623     1040  
Received at Least 1 Dose of Study Drug     3590     1033     3590     1027  
COMPLETED     3421     957     3417     958  
NOT COMPLETED     199     86     206     82  
Withdrawal by Subject                 194                 83                 202                 80  
Physician Decision                 3                 2                 1                 1  
Lost to Follow-up                 2                 1                 3                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Prasugrel: <75 Years of Age Prasugrel and Low-dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel : 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight) orally, once daily as maintenance dose through end of study.
Prasugrel: 75 Years of Age or Older Prasugrel and Low-dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 5 mg orally, once daily as maintenance dose through end of study.
Clopidogrel: <75 Years of Age Clopidogrel and Low-Dose Commercially-available Aspirin in participants less than (<) 75 years of age. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Clopidogrel: 75 Years of Age or Older Clopidogrel and Low-Dose Commercially-available Aspirin in participants 75 years of age or older. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.
Total Total of all reporting groups

Baseline Measures
    Prasugrel: <75 Years of Age     Prasugrel: 75 Years of Age or Older     Clopidogrel: <75 Years of Age     Clopidogrel: 75 Years of Age or Older     Total  
Number of Participants  
[units: participants]
  3620     1043     3623     1040     9326  
Age  
[units: years]
Mean ± Standard Deviation
  61.4  ± 8.55     80.3  ± 4.29     61.5  ± 8.38     80.3  ± 4.39     65.7  ± 11.02  
Gender  
[units: participants]
         
Female     1309     520     1290     531     3650  
Male     2311     523     2333     509     5676  
Race/Ethnicity, Customized  
[units: participants]
         
Caucasian     2362     767     2374     773     6276  
African     87     14     72     12     185  
Hispanic     321     109     346     86     862  
Asian     821     147     800     164     1932  
Other     29     6     30     5     70  
Unknown     0     0     1     0     1  
Region of Enrollment  
[units: participants]
         
Portugal     18     11     14     11     54  
Philippines     58     7     48     14     127  
Taiwan     6     6     4     9     25  
Slovakia     62     20     60     20     162  
Greece     14     8     10     11     43  
Costa Rica     5     1     2     2     10  
Thailand     30     17     36     10     93  
Ukraine     326     28     311     42     707  
Chile     28     15     33     13     89  
Italy     71     44     70     47     232  
India     513     56     508     64     1141  
France     29     22     29     19     99  
Denmark     21     7     17     10     55  
Korea, Republic of     35     7     33     7     82  
Panama     29     7     24     10     70  
Turkey     76     24     81     19     200  
Czech Republic     37     31     32     38     138  
Mexico     38     15     40     16     109  
Canada     58     14     61     13     146  
Brazil     154     27     147     34     362  
Romania     103     26     105     23     257  
Croatia     63     28     60     31     182  
Sweden     4     3     6     1     14  
United States     430     133     446     116     1125  
Serbia     42     4     40     5     91  
Spain     13     8     10     12     43  
Ireland     5     4     6     3     18  
Israel     75     33     85     21     214  
Russian Federation     128     22     135     14     299  
Colombia     40     21     45     17     123  
Switzerland     6     4     4     6     20  
Malaysia     35     7     33     9     84  
Peru     58     19     67     12     156  
Australia     13     6     15     7     41  
South Africa     27     11     27     12     77  
Netherlands     55     23     53     24     155  
Tunisia     20     3     20     4     47  
China     126     38     120     44     328  
Finland     3     3     5     2     13  
Lithuania     29     8     32     4     73  
Austria     6     6     6     5     23  
Malta     9     1     10     2     22  
United Kingdom     33     21     40     12     106  
Egypt     65     1     62     4     132  
Hungary     86     43     87     44     260  
Argentina     120     58     138     41     357  
Poland     137     59     129     68     393  
Belgium     7     7     7     8     29  
Singapore     2     5     5     1     13  
Bulgaria     216     48     209     55     528  
Germany     46     20     46     21     133  
New Zealand     10     3     10     3     26  
History of Diabetes  
[units: participants]
         
Yes     1393     363     1418     365     3539  
No     2221     678     2193     675     5767  
Unknown     6     2     12     0     20  
History of Myocardial Infarction (MI)  
[units: participants]
         
Yes     1556     426     1612     393     3987  
No     2035     603     1988     633     5259  
Unknown     29     14     23     14     80  
History of Coronary Revascularization (PCI or CABG) [1]
[units: participants]
         
Yes     1279     330     1365     299     3273  
No     2332     703     2239     734     6008  
Unknown     9     10     19     7     45  
Clinical Presentation of UA or NSTEMI [2]
[units: participants]
         
Unstable Angina     963     166     981     192     2302  
Non-ST-segment Elevation Myocardial Infarction     2453     829     2434     804     6520  
Unknown/Did not meet criteria     204     48     208     44     504  
[1] History of Coronary Revascularization due to percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG)
[2] Clinical Presentation of unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI)



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants With a Composite Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), or Stroke   [ Time Frame: Randomization through end of study (30-month visit) ]

2.  Secondary:   Percentage of Participants With a Composite Endpoint of CV Death and MI   [ Time Frame: Randomization through end of study (30-month visit) ]

3.  Secondary:   Percentage of Participants With a Composite Endpoint of CV Death, MI, Stroke, or Re-hospitalization for Recurrent Unstable Angina (UA)   [ Time Frame: Randomization through end of study (30-month visit) ]

4.  Secondary:   Percentage of Participants With a Composite Endpoint of All-cause Death, MI, or Stroke   [ Time Frame: Randomization through end of study (30-month visit) ]

5.  Secondary:   Platelet Aggregation Measures   [ Time Frame: Day 30 and 12 Months ]

6.  Secondary:   Biomarker Measurements of Inflammation/Hemodynamic Stress: Brain Natriuretic Peptide (BNP)   [ Time Frame: Day 30 and 6 Months ]

7.  Secondary:   Biomarker Measurements of Inflammation/Hemodynamic Stress: C-Reactive Protein (CRP)   [ Time Frame: Day 30 and Month 6 ]

8.  Secondary:   Genotyping Related to Drug Metabolism   [ Time Frame: Baseline ]

9.  Secondary:   Economic and Quality of Life Outcomes   [ Time Frame: Baseline and follow-up (24 months) ]

10.  Secondary:   Summary of All Deaths   [ Time Frame: Randomization through end of study (30-month visit) ]


  Serious Adverse Events
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Time Frame No text entered.
Additional Description Events leading to death, MI, stroke, stent thrombosis, or rehospitalization for recurrent UA were not recorded as an SAEs unless the event was possibly due to study drug.

Reporting Groups
  Description
Prasugrel Prasugrel and Low-dose Commercially-available Aspirin in participants. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study Prasugrel: 30 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and either 5 mg or 10 mg (based upon weight and age), oral, once daily as maintenance dose through end of study.
Clopidogrel Clopidogrel and Low-Dose Commercially-available Aspirin in participants. Commercially-available Aspirin: Low-dose aspirin, oral, as prescribed by physician through end of study. Clopidogrel: 300 milligram (mg), oral, once as loading dose (in those subjects who initiate study drug with a loading dose); and 75 mg, oral, once daily as maintenance dose through end of study.

Serious Adverse Events
    Prasugrel     Clopidogrel  
Total, serious adverse events      
# participants affected / at risk     1573/4623 (34.03%)     1594/4617 (34.52%)  
Blood and lymphatic system disorders      
Anaemia † 1    
# participants affected / at risk     23/4623 (0.50%)     23/4617 (0.50%)  
# events     23     23  
Anaemia haemolytic autoimmune † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Autoimmune thrombocytopenia † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Bicytopenia † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Coagulopathy † 1    
# participants affected / at risk     0/4623 (0.00%)     2/4617 (0.04%)  
# events     0     2  
Haemorrhagic anaemia † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Hypochromic anaemia † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Iron deficiency anaemia † 1    
# participants affected / at risk     3/4623 (0.06%)     5/4617 (0.11%)  
# events     3     5  
Microcytic anaemia † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Normochromic normocytic anaemia † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Pancytopenia † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Red blood cell abnormality † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Splenic infarction † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Thrombocytopenia † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Cardiac disorders      
Acute coronary syndrome † 1    
# participants affected / at risk     17/4623 (0.37%)     19/4617 (0.41%)  
# events     17     24  
Acute left ventricular failure † 1    
# participants affected / at risk     8/4623 (0.17%)     9/4617 (0.19%)  
# events     11     10  
Acute myocardial infarction † 1    
# participants affected / at risk     194/4623 (4.20%)     194/4617 (4.20%)  
# events     241     244  
Angina pectoris † 1    
# participants affected / at risk     115/4623 (2.49%)     129/4617 (2.79%)  
# events     125     139  
Angina unstable † 1    
# participants affected / at risk     290/4623 (6.27%)     310/4617 (6.71%)  
# events     351     374  
Aortic valve disease † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Aortic valve incompetence † 1    
# participants affected / at risk     2/4623 (0.04%)     2/4617 (0.04%)  
# events     2     2  
Aortic valve stenosis † 1    
# participants affected / at risk     2/4623 (0.04%)     1/4617 (0.02%)  
# events     2     1  
Arrhythmia † 1    
# participants affected / at risk     7/4623 (0.15%)     2/4617 (0.04%)  
# events     7     2  
Arrhythmia supraventricular † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Arteriosclerosis coronary artery † 1    
# participants affected / at risk     4/4623 (0.09%)     4/4617 (0.09%)  
# events     4     4  
Arteriospasm coronary † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Atrial fibrillation † 1    
# participants affected / at risk     82/4623 (1.77%)     69/4617 (1.49%)  
# events     88     71  
Atrial flutter † 1    
# participants affected / at risk     12/4623 (0.26%)     4/4617 (0.09%)  
# events     12     5  
Atrial tachycardia † 1    
# participants affected / at risk     2/4623 (0.04%)     3/4617 (0.06%)  
# events     2     3  
Atrial thrombosis † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Atrioventricular block † 1    
# participants affected / at risk     3/4623 (0.06%)     6/4617 (0.13%)  
# events     3     7  
Atrioventricular block complete † 1    
# participants affected / at risk     2/4623 (0.04%)     5/4617 (0.11%)  
# events     2     5  
Atrioventricular block second degree † 1    
# participants affected / at risk     0/4623 (0.00%)     2/4617 (0.04%)  
# events     0     2  
Bradyarrhythmia † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Bradycardia † 1    
# participants affected / at risk     7/4623 (0.15%)     14/4617 (0.30%)  
# events     8     14  
Bundle branch block left † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Bundle branch block right † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Cardiac arrest † 1    
# participants affected / at risk     29/4623 (0.63%)     28/4617 (0.61%)  
# events     30     28  
Cardiac disorder † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Cardiac failure † 1    
# participants affected / at risk     68/4623 (1.47%)     67/4617 (1.45%)  
# events     75     81  
Cardiac failure acute † 1    
# participants affected / at risk     12/4623 (0.26%)     19/4617 (0.41%)  
# events     12     19  
Cardiac failure chronic † 1    
# participants affected / at risk     36/4623 (0.78%)     41/4617 (0.89%)  
# events     36     41  
Cardiac failure congestive † 1    
# participants affected / at risk     83/4623 (1.80%)     104/4617 (2.25%)  
# events     96     111  
Cardiac flutter † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Cardiac tamponade † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Cardiac valve disease † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Cardio-respiratory arrest † 1    
# participants affected / at risk     8/4623 (0.17%)     14/4617 (0.30%)  
# events     8     14  
Cardiogenic shock † 1    
# participants affected / at risk     15/4623 (0.32%)     23/4617 (0.50%)  
# events     15     23  
Cardiomegaly † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Cardiomyopathy † 1    
# participants affected / at risk     3/4623 (0.06%)     1/4617 (0.02%)  
# events     3     1  
Cardiopulmonary failure † 1    
# participants affected / at risk     5/4623 (0.11%)     3/4617 (0.06%)  
# events     5     3  
Cardiovascular insufficiency † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Congestive cardiomyopathy † 1    
# participants affected / at risk     2/4623 (0.04%)     1/4617 (0.02%)  
# events     2     2  
Cor pulmonale † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Coronary artery disease † 1    
# participants affected / at risk     43/4623 (0.93%)     39/4617 (0.84%)  
# events     43     39  
Coronary artery dissection † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Coronary artery occlusion † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Coronary artery perforation † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Coronary artery stenosis † 1    
# participants affected / at risk     8/4623 (0.17%)     7/4617 (0.15%)  
# events     8     7  
Coronary artery thrombosis † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Diastolic dysfunction † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Ischaemic cardiomyopathy † 1    
# participants affected / at risk     4/4623 (0.09%)     3/4617 (0.06%)  
# events     4     3  
Left ventricular dysfunction † 1    
# participants affected / at risk     1/4623 (0.02%)     2/4617 (0.04%)  
# events     1     2  
Left ventricular failure † 1    
# participants affected / at risk     4/4623 (0.09%)     8/4617 (0.17%)  
# events     4     8  
Low cardiac output syndrome † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Mitral valve disease † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Mitral valve incompetence † 1    
# participants affected / at risk     2/4623 (0.04%)     1/4617 (0.02%)  
# events     2     1  
Myocardial fibrosis † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Myocardial infarction † 1    
# participants affected / at risk     142/4623 (3.07%)     143/4617 (3.10%)  
# events     166     166  
Myocardial ischaemia † 1    
# participants affected / at risk     31/4623 (0.67%)     41/4617 (0.89%)  
# events     31     41  
Palpitations † 1    
# participants affected / at risk     2/4623 (0.04%)     3/4617 (0.06%)  
# events     2     3  
Pericardial effusion † 1    
# participants affected / at risk     2/4623 (0.04%)     0/4617 (0.00%)  
# events     2     0  
Pericarditis † 1    
# participants affected / at risk     2/4623 (0.04%)     0/4617 (0.00%)  
# events     2     0  
Postinfarction angina † 1    
# participants affected / at risk     5/4623 (0.11%)     4/4617 (0.09%)  
# events     5     4  
Prinzmetal angina † 1    
# participants affected / at risk     2/4623 (0.04%)     0/4617 (0.00%)  
# events     2     0  
Sick sinus syndrome † 1    
# participants affected / at risk     1/4623 (0.02%)     3/4617 (0.06%)  
# events     1     3  
Sinus arrest † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Sinus bradycardia † 1    
# participants affected / at risk     2/4623 (0.04%)     1/4617 (0.02%)  
# events     2     1  
Stress cardiomyopathy † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Supraventricular tachycardia † 1    
# participants affected / at risk     4/4623 (0.09%)     8/4617 (0.17%)  
# events     4     8  
Tachycardia † 1    
# participants affected / at risk     1/4623 (0.02%)     3/4617 (0.06%)  
# events     1     3  
Ventricle rupture † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Ventricular arrhythmia † 1    
# participants affected / at risk     4/4623 (0.09%)     0/4617 (0.00%)  
# events     4     0  
Ventricular extrasystoles † 1    
# participants affected / at risk     2/4623 (0.04%)     5/4617 (0.11%)  
# events     2     5  
Ventricular fibrillation † 1    
# participants affected / at risk     3/4623 (0.06%)     15/4617 (0.32%)  
# events     3     17  
Ventricular tachycardia † 1    
# participants affected / at risk     15/4623 (0.32%)     20/4617 (0.43%)  
# events     17     23  
Congenital, familial and genetic disorders      
Branchial cyst † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Gastrointestinal angiodysplasia † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Glucose-6-phosphate dehydrogenase deficiency † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Hydrocele † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Phimosis † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Ear and labyrinth disorders      
Deafness unilateral † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Vertigo † 1    
# participants affected / at risk     5/4623 (0.11%)     4/4617 (0.09%)  
# events     5     4  
Vertigo positional † 1    
# participants affected / at risk     1/4623 (0.02%)     2/4617 (0.04%)  
# events     1     2  
Endocrine disorders      
Goitre † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Hyperthyroidism † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Primary hyperaldosteronism † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Primary hypothyroidism † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Eye disorders      
Amaurosis † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Cataract † 1    
# participants affected / at risk     8/4623 (0.17%)     4/4617 (0.09%)  
# events     9     5  
Conjunctival haemorrhage † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Corneal oedema † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Diabetic retinopathy † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     2  
Diplopia † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Eye haemorrhage † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Glaucoma † 1    
# participants affected / at risk     0/4623 (0.00%)     2/4617 (0.04%)  
# events     0     2  
Open angle glaucoma † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Ophthalmoplegia † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Retinal artery occlusion † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Retinal detachment † 1    
# participants affected / at risk     0/4623 (0.00%)     2/4617 (0.04%)  
# events     0     3  
Retinal haemorrhage † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Retinal vein thrombosis † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Vision blurred † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Vitreous haemorrhage † 1    
# participants affected / at risk     1/4623 (0.02%)     2/4617 (0.04%)  
# events     1     2  
Gastrointestinal disorders      
Abdominal adhesions † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Abdominal hernia † 1    
# participants affected / at risk     2/4623 (0.04%)     2/4617 (0.04%)  
# events     2     2  
Abdominal hernia obstructive † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Abdominal pain † 1    
# participants affected / at risk     6/4623 (0.13%)     6/4617 (0.13%)  
# events     6     6  
Abdominal pain lower † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Abdominal pain upper † 1    
# participants affected / at risk     3/4623 (0.06%)     4/4617 (0.09%)  
# events     3     4  
Abdominal wall haematoma † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Acute abdomen † 1    
# participants affected / at risk     2/4623 (0.04%)     0/4617 (0.00%)  
# events     2     0  
Anal fissure † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Anal fistula † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Ascites † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Colitis † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Colitis ischaemic † 1    
# participants affected / at risk     1/4623 (0.02%)     2/4617 (0.04%)  
# events     1     2  
Colonic polyp † 1    
# participants affected / at risk     3/4623 (0.06%)     2/4617 (0.04%)  
# events     3     2  
Constipation † 1    
# participants affected / at risk     2/4623 (0.04%)     3/4617 (0.06%)  
# events     2     3  
Dental caries † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Diarrhoea † 1    
# participants affected / at risk     1/4623 (0.02%)     4/4617 (0.09%)  
# events     1     4  
Diarrhoea haemorrhagic † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Diverticulum † 1    
# participants affected / at risk     1/4623 (0.02%)     2/4617 (0.04%)  
# events     1     2  
Diverticulum intestinal † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Diverticulum intestinal haemorrhagic † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Duodenal polyp † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Duodenal ulcer † 1    
# participants affected / at risk     6/4623 (0.13%)     4/4617 (0.09%)  
# events     6     4  
Duodenal ulcer haemorrhage † 1    
# participants affected / at risk     4/4623 (0.09%)     2/4617 (0.04%)  
# events     4     2  
Duodenitis † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Dyspepsia † 1    
# participants affected / at risk     5/4623 (0.11%)     2/4617 (0.04%)  
# events     5     2  
Dysphagia † 1    
# participants affected / at risk     3/4623 (0.06%)     4/4617 (0.09%)  
# events     3     4  
Enteritis † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Epigastric discomfort † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Erosive duodenitis † 1    
# participants affected / at risk     2/4623 (0.04%)     0/4617 (0.00%)  
# events     2     0  
Faecaloma † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Femoral hernia † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Gastric disorder † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Gastric haemorrhage † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Gastric ulcer † 1    
# participants affected / at risk     3/4623 (0.06%)     1/4617 (0.02%)  
# events     3     1  
Gastric ulcer haemorrhage † 1    
# participants affected / at risk     3/4623 (0.06%)     2/4617 (0.04%)  
# events     3     2  
Gastric ulcer, obstructive † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Gastritis † 1    
# participants affected / at risk     11/4623 (0.24%)     4/4617 (0.09%)  
# events     11     4  
Gastritis erosive † 1    
# participants affected / at risk     2/4623 (0.04%)     3/4617 (0.06%)  
# events     2     3  
Gastritis haemorrhagic † 1    
# participants affected / at risk     0/4623 (0.00%)     2/4617 (0.04%)  
# events     0     2  
Gastrointestinal disorder † 1    
# participants affected / at risk     2/4623 (0.04%)     1/4617 (0.02%)  
# events     2     1  
Gastrointestinal haemorrhage † 1    
# participants affected / at risk     39/4623 (0.84%)     22/4617 (0.48%)  
# events     39     22  
Gastrointestinal inflammation † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Gastrointestinal pain † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Gastrointestinal ulcer haemorrhage † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Gastrooesophageal reflux disease † 1    
# participants affected / at risk     6/4623 (0.13%)     3/4617 (0.06%)  
# events     6     3  
Gingival bleeding † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Haematemesis † 1    
# participants affected / at risk     6/4623 (0.13%)     0/4617 (0.00%)  
# events     6     0  
Haematochezia † 1    
# participants affected / at risk     2/4623 (0.04%)     2/4617 (0.04%)  
# events     2     2  
Haemorrhagic erosive gastritis † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Haemorrhoidal haemorrhage † 1    
# participants affected / at risk     1/4623 (0.02%)     3/4617 (0.06%)  
# events     1     3  
Haemorrhoids † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Hiatus hernia † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Ileus † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Ileus paralytic † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Impaired gastric emptying † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Inguinal hernia † 1    
# participants affected / at risk     2/4623 (0.04%)     6/4617 (0.13%)  
# events     3     6  
Inguinal hernia strangulated † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Inguinal hernia, obstructive † 1    
# participants affected / at risk     1/4623 (0.02%)     2/4617 (0.04%)  
# events     1     2  
Intestinal angina † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Intestinal fistula † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Intestinal haemorrhage † 1    
# participants affected / at risk     1/4623 (0.02%)     2/4617 (0.04%)  
# events     1     2  
Intestinal ischaemia † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Intestinal mass † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Intestinal obstruction † 1    
# participants affected / at risk     1/4623 (0.02%)     3/4617 (0.06%)  
# events     1     3  
Irritable bowel syndrome † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Localised intraabdominal fluid collection † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Lower gastrointestinal haemorrhage † 1    
# participants affected / at risk     8/4623 (0.17%)     3/4617 (0.06%)  
# events     8     3  
Mallory-weiss syndrome † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Melaena † 1    
# participants affected / at risk     4/4623 (0.09%)     1/4617 (0.02%)  
# events     4     1  
Mesenteric artery embolism † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Nausea † 1    
# participants affected / at risk     1/4623 (0.02%)     2/4617 (0.04%)  
# events     1     2  
Oesophageal ulcer † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Oesophageal ulcer haemorrhage † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Oesophagitis † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Palatal oedema † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Pancreatitis † 1    
# participants affected / at risk     1/4623 (0.02%)     5/4617 (0.11%)  
# events     1     6  
Pancreatitis acute † 1    
# participants affected / at risk     2/4623 (0.04%)     5/4617 (0.11%)  
# events     2     5  
Pancreatitis chronic † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Pancreatitis haemorrhagic † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Pancreatitis relapsing † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Peptic ulcer † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Rectal haemorrhage † 1    
# participants affected / at risk     11/4623 (0.24%)     4/4617 (0.09%)  
# events     12     4  
Retroperitoneal haemorrhage † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Sigmoiditis † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Small intestinal obstruction † 1    
# participants affected / at risk     3/4623 (0.06%)     3/4617 (0.06%)  
# events     5     4  
Small intestinal perforation † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Subileus † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Umbilical hernia † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Upper gastrointestinal haemorrhage † 1    
# participants affected / at risk     20/4623 (0.43%)     15/4617 (0.32%)  
# events     21     15  
Varices oesophageal † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Vomiting † 1    
# participants affected / at risk     2/4623 (0.04%)     1/4617 (0.02%)  
# events     2     1  
General disorders      
Adverse drug reaction † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Asthenia † 1    
# participants affected / at risk     8/4623 (0.17%)     3/4617 (0.06%)  
# events     8     3  
Cardiac death † 1    
# participants affected / at risk     2/4623 (0.04%)     1/4617 (0.02%)  
# events     2     1  
Chest discomfort † 1    
# participants affected / at risk     3/4623 (0.06%)     4/4617 (0.09%)  
# events     3     4  
Chest pain † 1    
# participants affected / at risk     13/4623 (0.28%)     5/4617 (0.11%)  
# events     14     6  
Chills † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Death † 1    
# participants affected / at risk     34/4623 (0.74%)     40/4617 (0.87%)  
# events     34     40  
Device malfunction † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Euthanasia † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Generalised oedema † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Hernia † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Impaired healing † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Malaise † 1    
# participants affected / at risk     2/4623 (0.04%)     0/4617 (0.00%)  
# events     2     0  
Medical device complication † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Multi-organ failure † 1    
# participants affected / at risk     3/4623 (0.06%)     5/4617 (0.11%)  
# events     3     5  
Necrosis † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Non-cardiac chest pain † 1    
# participants affected / at risk     66/4623 (1.43%)     65/4617 (1.41%)  
# events     71     78  
Oedema peripheral † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Pyrexia † 1    
# participants affected / at risk     3/4623 (0.06%)     3/4617 (0.06%)  
# events     3     3  
Sudden cardiac death † 1    
# participants affected / at risk     12/4623 (0.26%)     16/4617 (0.35%)  
# events     12     16  
Sudden death † 1    
# participants affected / at risk     45/4623 (0.97%)     46/4617 (1.00%)  
# events     45     46  
Thrombosis in device † 1    
# participants affected / at risk     12/4623 (0.26%)     23/4617 (0.50%)  
# events     13     24  
Ulcer haemorrhage † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Hepatobiliary disorders      
Bile duct obstruction † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Bile duct stone † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Biliary tract disorder † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Cholecystitis † 1    
# participants affected / at risk     6/4623 (0.13%)     4/4617 (0.09%)  
# events     6     4  
Cholecystitis acute † 1    
# participants affected / at risk     9/4623 (0.19%)     8/4617 (0.17%)  
# events     10     9  
Cholecystitis chronic † 1    
# participants affected / at risk     1/4623 (0.02%)     3/4617 (0.06%)  
# events     1     3  
Cholelithiasis † 1    
# participants affected / at risk     4/4623 (0.09%)     10/4617 (0.22%)  
# events     4     10  
Cholestasis † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Hepatic cirrhosis † 1    
# participants affected / at risk     4/4623 (0.09%)     0/4617 (0.00%)  
# events     4     0  
Hepatic failure † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Hepatitis † 1    
# participants affected / at risk     0/4623 (0.00%)     2/4617 (0.04%)  
# events     0     2  
Hyperplastic cholecystopathy † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Portal vein thrombosis † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Immune system disorders      
Atopy † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Drug hypersensitivity † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Hypersensitivity † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Immunosuppression † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Kidney transplant rejection † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     2  
Infections and infestations      
Abdominal abscess † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Abdominal sepsis † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Abdominal wall abscess † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Abscess limb † 1    
# participants affected / at risk     2/4623 (0.04%)     1/4617 (0.02%)  
# events     2     1  
Abscess neck † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     2  
Acute sinusitis † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Anal abscess † 1    
# participants affected / at risk     1/4623 (0.02%)     2/4617 (0.04%)  
# events     1     2  
Appendiceal abscess † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Appendicitis † 1    
# participants affected / at risk     1/4623 (0.02%)     3/4617 (0.06%)  
# events     1     3  
Appendicitis perforated † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Bacteraemia † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Bronchitis † 1    
# participants affected / at risk     11/4623 (0.24%)     15/4617 (0.32%)  
# events     12     15  
Bronchitis bacterial † 1    
# participants affected / at risk     0/4623 (0.00%)     2/4617 (0.04%)  
# events     0     2  
Bronchopneumonia † 1    
# participants affected / at risk     8/4623 (0.17%)     8/4617 (0.17%)  
# events     8     10  
Bronchopulmonary aspergillosis † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Burkholderia cepacia complex infection † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Burkholderia pseudomallei infection † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Cellulitis † 1    
# participants affected / at risk     9/4623 (0.19%)     11/4617 (0.24%)  
# events     9     12  
Cholecystitis infective † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Cystitis † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Cytomegalovirus colitis † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Device related infection † 1    
# participants affected / at risk     2/4623 (0.04%)     0/4617 (0.00%)  
# events     2     0  
Diabetic gangrene † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Diarrhoea infectious † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Disseminated tuberculosis † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Diverticulitis † 1    
# participants affected / at risk     3/4623 (0.06%)     1/4617 (0.02%)  
# events     3     1  
Ear infection † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Eczema infected † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Enterocolitis bacterial † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Erysipelas † 1    
# participants affected / at risk     2/4623 (0.04%)     5/4617 (0.11%)  
# events     2     5  
Escherichia urinary tract infection † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Fungal infection † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Furuncle † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Gangrene † 1    
# participants affected / at risk     4/4623 (0.09%)     1/4617 (0.02%)  
# events     4     1  
Gastroenteritis † 1    
# participants affected / at risk     7/4623 (0.15%)     7/4617 (0.15%)  
# events     7     7  
Gastroenteritis norovirus † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Gastroenteritis viral † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Gastrointestinal viral infection † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Groin abscess † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Haematoma infection † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Helicobacter gastritis † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Hepatitis b † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Hepatitis c † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Herpes zoster † 1    
# participants affected / at risk     2/4623 (0.04%)     0/4617 (0.00%)  
# events     2     0  
Herpes zoster ophthalmic † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Infection † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Infectious peritonitis † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Infective exacerbation of chronic obstructive airways disease † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Labyrinthitis † 1    
# participants affected / at risk     2/4623 (0.04%)     1/4617 (0.02%)  
# events     2     1  
Lobar pneumonia † 1    
# participants affected / at risk     2/4623 (0.04%)     1/4617 (0.02%)  
# events     2     1  
Localised infection † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Lower respiratory tract infection † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Lower respiratory tract infection viral † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Lung abscess † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Lung infection † 1    
# participants affected / at risk     0/4623 (0.00%)     2/4617 (0.04%)  
# events     0     2  
Lymphangitis † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Malaria † 1    
# participants affected / at risk     2/4623 (0.04%)     0/4617 (0.00%)  
# events     2     0  
Mediastinitis † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Meningitis tuberculous † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Muscle abscess † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Onychomycosis † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Orchitis † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Osteomyelitis † 1    
# participants affected / at risk     5/4623 (0.11%)     4/4617 (0.09%)  
# events     5     4  
Osteomyelitis chronic † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Parametritis † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Paronychia † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Peridiverticular abscess † 1    
# participants affected / at risk     2/4623 (0.04%)     0/4617 (0.00%)  
# events     2     0  
Perirectal abscess † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Pneumonia † 1    
# participants affected / at risk     74/4623 (1.60%)     76/4617 (1.65%)  
# events     86     79  
Pneumonia bacterial † 1    
# participants affected / at risk     2/4623 (0.04%)     0/4617 (0.00%)  
# events     2     0  
Pneumonia haemophilus † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Pneumonia mycoplasmal † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Pneumonia staphylococcal † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Pneumonia viral † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Post procedural infection † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Postoperative wound infection † 1    
# participants affected / at risk     2/4623 (0.04%)     1/4617 (0.02%)  
# events     2     1  
Pulmonary tuberculosis † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Pyelonephritis † 1    
# participants affected / at risk     1/4623 (0.02%)     2/4617 (0.04%)  
# events     1     2  
Pyelonephritis acute † 1    
# participants affected / at risk     2/4623 (0.04%)     2/4617 (0.04%)  
# events     2     2  
Pyelonephritis chronic † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Pyonephrosis † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Rectal abscess † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Renal abscess † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Respiratory tract infection † 1    
# participants affected / at risk     3/4623 (0.06%)     7/4617 (0.15%)  
# events     3     7  
Salmonellosis † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Scrotal abscess † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Sepsis † 1    
# participants affected / at risk     11/4623 (0.24%)     12/4617 (0.26%)  
# events     11     12  
Septic shock † 1    
# participants affected / at risk     6/4623 (0.13%)     8/4617 (0.17%)  
# events     6     8  
Sinusitis † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Skin infection † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Staphylococcal bacteraemia † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Staphylococcal infection † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Staphylococcal sepsis † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Subcutaneous abscess † 1    
# participants affected / at risk     2/4623 (0.04%)     0/4617 (0.00%)  
# events     2     0  
Tracheobronchitis † 1    
# participants affected / at risk     2/4623 (0.04%)     2/4617 (0.04%)  
# events     2     2  
Tuberculosis † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Upper respiratory tract infection † 1    
# participants affected / at risk     2/4623 (0.04%)     2/4617 (0.04%)  
# events     2     2  
Urinary tract infection † 1    
# participants affected / at risk     33/4623 (0.71%)     19/4617 (0.41%)  
# events     34     20  
Urosepsis † 1    
# participants affected / at risk     4/4623 (0.09%)     3/4617 (0.06%)  
# events     4     3  
Viral diarrhoea † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Viral infection † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Viral upper respiratory tract infection † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Wound infection † 1    
# participants affected / at risk     1/4623 (0.02%)     2/4617 (0.04%)  
# events     1     2  
Injury, poisoning and procedural complications      
Accidental overdose † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Alcohol poisoning † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Ankle fracture † 1    
# participants affected / at risk     2/4623 (0.04%)     4/4617 (0.09%)  
# events     2     4  
Arteriovenous fistula site haemorrhage † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Brain contusion † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Chemical burns of eye † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Concussion † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Confusion postoperative † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Contusion † 1    
# participants affected / at risk     1/4623 (0.02%)     3/4617 (0.06%)  
# events     1     3  
Coronary artery restenosis † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Face injury † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Facial bones fracture † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Fall † 1    
# participants affected / at risk     5/4623 (0.11%)     1/4617 (0.02%)  
# events     5     1  
Femoral neck fracture † 1    
# participants affected / at risk     1/4623 (0.02%)     3/4617 (0.06%)  
# events     1     3  
Femur fracture † 1    
# participants affected / at risk     7/4623 (0.15%)     7/4617 (0.15%)  
# events     7     7  
Fibula fracture † 1    
# participants affected / at risk     0/4623 (0.00%)     2/4617 (0.04%)  
# events     0     2  
Foot fracture † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Gun shot wound † 1    
# participants affected / at risk     1/4623 (0.02%)     2/4617 (0.04%)  
# events     1     2  
Haematuria traumatic † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Hand fracture † 1    
# participants affected / at risk     2/4623 (0.04%)     1/4617 (0.02%)  
# events     2     1  
Head injury † 1    
# participants affected / at risk     2/4623 (0.04%)     1/4617 (0.02%)  
# events     2     1  
Hip fracture † 1    
# participants affected / at risk     6/4623 (0.13%)     6/4617 (0.13%)  
# events     6     6  
Humerus fracture † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
In-stent coronary artery restenosis † 1    
# participants affected / at risk     3/4623 (0.06%)     7/4617 (0.15%)  
# events     3     7  
Incisional hernia, obstructive † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Joint dislocation † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Limb injury † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Lower limb fracture † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)  
# events     1     0  
Lumbar vertebral fracture † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Multiple drug overdose † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Muscle rupture † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Operative haemorrhage † 1    
# participants affected / at risk     0/4623 (0.00%)     2/4617 (0.04%)  
# events     0     2  
Overdose † 1    
# participants affected / at risk     0/4623 (0.00%)     1/4617 (0.02%)  
# events     0     1  
Pelvic fracture † 1    
# participants affected / at risk     1/4623 (0.02%)     1/4617 (0.02%)  
# events     1     1  
Periorbital haematoma † 1    
# participants affected / at risk     1/4623 (0.02%)     0/4617 (0.00%)