Venous Thromboembolic Event (VTE) Prophylaxis in Medically Ill Patients (MAGELLAN)

This study has been completed.
Sponsor:
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by:
Bayer
ClinicalTrials.gov Identifier:
NCT00571649
First received: December 11, 2007
Last updated: June 13, 2013
Last verified: June 2013
Results First Received: February 16, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition: Venous Thromboembolism
Interventions: Drug: Rivaroxaban (Xarelto, BAY59-7939)
Drug: Enoxaparin
Drug: Rivaroxaban placebo
Drug: Enoxaparin placebo

  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
First patient first visit date: 04 DEC 2007; last patient last visit date 24 NOV 2010. Primary completion date: 12 AUG 2010. Participants were aged ≥40 years, hospitalized for an acute medical illness, and at risk of Venous Thromboembolism (VTE) (with heart failure, cancer, ischemic stroke, infection or inflammation, or respiratory insufficiency)

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 8428 participants were screened; 327 failed. 8101 were randomized. 7998 (98.7%) were in the Safety Analysis Set (SAF), i.e. received study medication. 6024 (74.4%) were in the modified Intent to Treat (at Day 35) group (valid for SAF with adequate assessment of venous thromboembolism). A total of 6005 (74.1%) completed study.

Reporting Groups
  Description
Rivaroxaban (Xarelto, BAY59-7939) Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days during treatment period
Enoxaparin Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days during treatment period

Participant Flow for 2 periods

Period 1:   Treatment Period
    Rivaroxaban (Xarelto, BAY59-7939)     Enoxaparin  
STARTED     4050     4051  
Participants Received Treatment     3997     4001  
Day 10     3454     3499  
Day 35     3033     3115  
COMPLETED     2958     3047  
NOT COMPLETED     1092     1004  
Adverse Event                 438                 385  
Clinical endpoint reached                 50                 56  
Withdrawal by Subject                 285                 255  
Death                 76                 59  
Physician Decision                 8                 9  
Lost to Follow-up                 43                 41  
Non-compliant with study medication                 88                 89  
Patient convenience                 11                 13  
Protocol Violation                 90                 92  
Technical problems                 3                 5  

Period 2:   Follow-up Period
    Rivaroxaban (Xarelto, BAY59-7939)     Enoxaparin  
STARTED     3583 [1]   3635 [1]
COMPLETED     3038 [2]   3107 [2]
NOT COMPLETED     545     528  
Adverse Event                 46                 40  
Clinical endpoint reached                 5                 2  
Withdrawal by Subject                 119                 115  
Death                 132                 133  
Physician Decision                 7                 13  
Lost to Follow-up                 95                 92  
Patient convenience                 136                 121  
Protocol Violation                 5                 12  
[1] Participants were required to enter follow-up even if treatment period not completed.
[2] Began day after last dose study drug; ended on Day 90 (+/- 7 days) .



  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
Rivaroxaban (Xarelto, BAY59-7939) Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days (SAF population)
Enoxaparin Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days (SAF population)
Total Total of all reporting groups

Baseline Measures
    Rivaroxaban (Xarelto, BAY59-7939)     Enoxaparin     Total  
Number of Participants  
[units: participants]
  3997     4001     7998  
Age  
[units: years]
Mean ± Standard Deviation
  69.2  ± 11.9     69.2  ± 11.7     69.2  ± 11.8  
Age, Customized  
[units: participants]
     
< 65 years     1323     1363     2686  
65 to < 75 years     1144     1090     2234  
>= 75 years     1530     1548     3078  
Gender  
[units: participants]
     
Female     1774     1898     3672  
Male     2223     2103     4326  
Race  
[units: participants]
     
White     2749     2744     5493  
Black     89     92     181  
Asian     793     794     1587  
Native American     12     12     24  
Hispanic     69     70     139  
Uncodable     106     112     218  
Unknown     1     0     1  
Missing     178     177     355  
Reason for hospitalization [1]
[units: participants]
     
Heart failure (NYHA Class III or NYHA Class IV)     1292     1301     2593  
Active cancer     294     290     584  
Acute ischemic stroke     691     692     1383  
Acute Infectious and Inflammatory Diseases     1904     1876     3780  
Acute infectious disease     1826     1801     3627  
Acute inflammatory or rheumatic disease     150     149     299  
Acute respiratory insufficiency     1085     1151     2236  
[1] Participants may have more than one acute condition as hospitalization reason. Acute medical illnesses included heart failure (New York Heart Association [NYHA] Class III [marked limitation of physical activity] or NYHA Class IV [inability to carry out any physical activity without discomfort)] active cancer, acute ischemic stroke, acute infectious and inflammatory diseases (including acute rheumatic diseases), acute respiratory insufficiency.



  Outcome Measures
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1.  Primary:   Percentage of Participants With Composite Endpoint of Venous Thromboembolism [VTE] (Any Deep Vein Thrombosis [DVT], Non Fatal Pulmonary Embolism [PE]) and VTE-related Death up to Day 35 + 6 Days   [ Time Frame: Up to Day 35 + 6 days ]

2.  Primary:   Percentage of Participants With Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 10 + 5 Days   [ Time Frame: Up to Day 10 + 5 days ]

3.  Secondary:   Percentage of Participants With Composite Endpoint of VTE (Any DVT, Non Fatal PE) and All-cause Mortality up to Day 35 + 6 Days   [ Time Frame: Up to Day 35 + 6 days ]

4.  Secondary:   Percentage of Participants With Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 10 + 5 Days Per mITT Population   [ Time Frame: Up to Day 10 + 5 days ]

5.  Secondary:   Percentage of Participants With VTE Combined With All-cause Mortality up to Day 10 + 5 Days   [ Time Frame: Up to Day 10 + 5 days ]

6.  Secondary:   Percentage of Participants With Symptomatic VTE, Including and Excluding VTE-related Death up to Days 10, 35, and 90   [ Time Frame: At Day 10 + 5 days, at Day 35 + 6 days, and at Day 90 + 7 days ]

7.  Secondary:   Percentage of Participants With Net Clinical Benefit (Any DVT, Non-fatal PE, VTE-related Death, Plus Major and Clinically Relevant Non-major Bleeding Events) up to Day 35 + 6 Days   [ Time Frame: Up to Day 35 + 6 days ]

8.  Secondary:   Percentage of Participants With Net Clinical Benefit (Any DVT, Non-fatal PE, VTE-related Death, Plus Major and Clinically Relevant Non-major Bleeding Events) up to Day 10 + 5 Days   [ Time Frame: Up to Day 10 + 5 days ]

9.  Secondary:   Percentage of Participants With Major Vascular Events up to Days 10, 35, and 90   [ Time Frame: At Day 10 + 5 days, at Day 35 + 6 days, and at Day 90 + 7 days ]

10.  Secondary:   Percentage of Participants With Each Component of the Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 35 + 6 Days   [ Time Frame: Up to Day 35 + 6 days ]

11.  Secondary:   Percentage of Participants With Each Component of the Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 10 + 5 Days   [ Time Frame: Up to Day 10 + 5 days ]

12.  Secondary:   Percentage of Participants With All-cause Mortality up to Day 90 + 7 Days   [ Time Frame: Up to Day 90 + 7 days ]

13.  Secondary:   Percentage of Participants With the Composite of Treatment Emergent Major Bleeding Events and Non-major Clinically Relevant Bleeding Events up to 2 Days After Last Intake of Any Study Medication (Day 35 + 6 Days)   [ Time Frame: Up to Day 35 + 6 days ]

14.  Secondary:   Percentage of Participants With the Composite of Treatment Emergent Major Bleeding Events and Non-major Clinically Relevant Bleeding Events up to 2 Days After Last Application of a Study Medication Syringe (Day 10 + 5 Days)   [ Time Frame: Up to Day 10 + 5 days ]


  Serious Adverse Events
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Reporting Groups
  Description
Rivaroxaban (Xarelto, BAY59-7939) Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days
Enoxaparin Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days

Serious Adverse Events
    Rivaroxaban (Xarelto, BAY59-7939)     Enoxaparin  
Total, serious adverse events      
# participants affected / at risk     1034/3997 (25.87%)     976/4001 (24.39%)  
Blood and lymphatic system disorders      
Agranulocytosis * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Anaemia * 1    
# participants affected / at risk     18/3997 (0.45%)     13/4001 (0.32%)  
# events     20     13  
Coagulopathy * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Disseminated intravascular coagulation * 1    
# participants affected / at risk     2/3997 (0.05%)     2/4001 (0.05%)  
# events     2     2  
Febrile neutropenia * 1    
# participants affected / at risk     4/3997 (0.10%)     3/4001 (0.07%)  
# events     5     4  
Leukocytosis * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Leukopenia * 1    
# participants affected / at risk     0/3997 (0.00%)     2/4001 (0.05%)  
# events     0     2  
Lymphadenopathy * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Neutropenia * 1    
# participants affected / at risk     0/3997 (0.00%)     3/4001 (0.07%)  
# events     0     3  
Normochromic normocytic anaemia * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Pancytopenia * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Thrombocytopenia * 1    
# participants affected / at risk     13/3997 (0.33%)     9/4001 (0.22%)  
# events     13     9  
Anaemia of malignant disease * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Haemorrhagic anaemia * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Heparin-induced thrombocytopenia * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Cardiac disorders      
Acute myocardial infarction * 1    
# participants affected / at risk     30/3997 (0.75%)     28/4001 (0.70%)  
# events     31     29  
Angina pectoris * 1    
# participants affected / at risk     1/3997 (0.03%)     4/4001 (0.10%)  
# events     1     4  
Angina unstable * 1    
# participants affected / at risk     6/3997 (0.15%)     6/4001 (0.15%)  
# events     7     6  
Aortic valve incompetence * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Aortic valve stenosis * 1    
# participants affected / at risk     2/3997 (0.05%)     0/4001 (0.00%)  
# events     2     0  
Arrhythmia * 1    
# participants affected / at risk     2/3997 (0.05%)     6/4001 (0.15%)  
# events     2     6  
Arteriosclerosis coronary artery * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Atrial fibrillation * 1    
# participants affected / at risk     23/3997 (0.58%)     22/4001 (0.55%)  
# events     23     24  
Atrial flutter * 1    
# participants affected / at risk     5/3997 (0.13%)     2/4001 (0.05%)  
# events     5     2  
Atrial tachycardia * 1    
# participants affected / at risk     2/3997 (0.05%)     0/4001 (0.00%)  
# events     2     0  
Atrioventricular block * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Atrioventricular block complete * 1    
# participants affected / at risk     3/3997 (0.08%)     5/4001 (0.12%)  
# events     3     5  
Bradycardia * 1    
# participants affected / at risk     1/3997 (0.03%)     4/4001 (0.10%)  
# events     1     4  
Cardiac arrest * 1    
# participants affected / at risk     12/3997 (0.30%)     11/4001 (0.27%)  
# events     13     12  
Cardiac failure * 1    
# participants affected / at risk     76/3997 (1.90%)     76/4001 (1.90%)  
# events     84     81  
Cardiac failure acute * 1    
# participants affected / at risk     11/3997 (0.28%)     25/4001 (0.62%)  
# events     12     28  
Cardiac failure chronic * 1    
# participants affected / at risk     10/3997 (0.25%)     10/4001 (0.25%)  
# events     10     11  
Cardiac failure congestive * 1    
# participants affected / at risk     31/3997 (0.78%)     31/4001 (0.77%)  
# events     37     38  
Cardiac hypertrophy * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Cardio-respiratory arrest * 1    
# participants affected / at risk     11/3997 (0.28%)     12/4001 (0.30%)  
# events     11     12  
Cardiogenic shock * 1    
# participants affected / at risk     6/3997 (0.15%)     4/4001 (0.10%)  
# events     6     4  
Cardiomegaly * 1    
# participants affected / at risk     0/3997 (0.00%)     2/4001 (0.05%)  
# events     0     2  
Cardiomyopathy * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Cardiovascular disorder * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     2  
Cor pulmonale * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Cor pulmonale chronic * 1    
# participants affected / at risk     2/3997 (0.05%)     1/4001 (0.02%)  
# events     2     1  
Coronary artery disease * 1    
# participants affected / at risk     12/3997 (0.30%)     7/4001 (0.17%)  
# events     13     8  
Coronary artery occlusion * 1    
# participants affected / at risk     1/3997 (0.03%)     2/4001 (0.05%)  
# events     1     2  
Coronary artery stenosis * 1    
# participants affected / at risk     1/3997 (0.03%)     3/4001 (0.07%)  
# events     1     3  
Left ventricular failure * 1    
# participants affected / at risk     2/3997 (0.05%)     2/4001 (0.05%)  
# events     2     2  
Myocardial infarction * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Myocardial ischaemia * 1    
# participants affected / at risk     3/3997 (0.08%)     6/4001 (0.15%)  
# events     3     6  
Palpitations * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Pericardial effusion * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Pericardial haemorrhage * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Pericarditis * 1    
# participants affected / at risk     2/3997 (0.05%)     1/4001 (0.02%)  
# events     2     1  
Right ventricular failure * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Sick sinus syndrome * 1    
# participants affected / at risk     2/3997 (0.05%)     3/4001 (0.07%)  
# events     2     3  
Sinus arrest * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Sinus bradycardia * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Supraventricular tachycardia * 1    
# participants affected / at risk     3/3997 (0.08%)     1/4001 (0.02%)  
# events     3     1  
Trifascicular block * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Ventricular fibrillation * 1    
# participants affected / at risk     4/3997 (0.10%)     3/4001 (0.07%)  
# events     6     3  
Ventricular tachycardia * 1    
# participants affected / at risk     7/3997 (0.18%)     1/4001 (0.02%)  
# events     8     2  
Intracardiac thrombus * 1    
# participants affected / at risk     1/3997 (0.03%)     3/4001 (0.07%)  
# events     1     3  
Atrial thrombosis * 1    
# participants affected / at risk     4/3997 (0.10%)     0/4001 (0.00%)  
# events     4     0  
Ischaemic cardiomyopathy * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Tachyarrhythmia * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Left ventricular dysfunction * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Bradyarrhythmia * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Electromechanical dissociation * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Cardiopulmonary failure * 1    
# participants affected / at risk     5/3997 (0.13%)     8/4001 (0.20%)  
# events     5     8  
Acute coronary syndrome * 1    
# participants affected / at risk     2/3997 (0.05%)     2/4001 (0.05%)  
# events     2     2  
Haemorrhage coronary artery * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Congestive cardiomyopathy * 1    
# participants affected / at risk     1/3997 (0.03%)     2/4001 (0.05%)  
# events     1     2  
Cardiac perforation * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Right ventricular dysfunction * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Mitral valve disease * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Cardiac fibrillation * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Rheumatic heart disease * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Acute left ventricular failure * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Supraventricular tachyarrhythmia * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Cardiovascular insufficiency * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Chronotropic incompetence * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Atrioventricular dissociation * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Congenital, familial and genetic disorders      
Atrial septal defect * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Gastrointestinal angiodysplasia * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Pyloric stenosis * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Myotonic dystrophy * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Ear and labyrinth disorders      
Ear haemorrhage * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Vertigo * 1    
# participants affected / at risk     2/3997 (0.05%)     2/4001 (0.05%)  
# events     2     2  
Eye disorders      
Cataract * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Conjunctival haemorrhage * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Diabetic retinopathy * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Eye haemorrhage * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Eye pain * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Glaucoma * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Keratitis * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Macular degeneration * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Macular oedema * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Optic atrophy * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Periorbital oedema * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Pupils unequal * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Retinopathy hypertensive * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Vision blurred * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Vitreous haemorrhage * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Entropion * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Gastrointestinal disorders      
Abdominal pain * 1    
# participants affected / at risk     6/3997 (0.15%)     4/4001 (0.10%)  
# events     7     5  
Abdominal pain upper * 1    
# participants affected / at risk     2/3997 (0.05%)     2/4001 (0.05%)  
# events     2     2  
Acute abdomen * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Ascites * 1    
# participants affected / at risk     2/3997 (0.05%)     0/4001 (0.00%)  
# events     2     0  
Colitis * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Colitis ischaemic * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Colonic polyp * 1    
# participants affected / at risk     0/3997 (0.00%)     2/4001 (0.05%)  
# events     0     2  
Constipation * 1    
# participants affected / at risk     2/3997 (0.05%)     3/4001 (0.07%)  
# events     2     3  
Diarrhoea * 1    
# participants affected / at risk     5/3997 (0.13%)     10/4001 (0.25%)  
# events     6     11  
Diarrhoea haemorrhagic * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Diverticulum * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Diverticulum intestinal * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Diverticulum intestinal haemorrhagic * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Duodenal ulcer * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Duodenal ulcer haemorrhage * 1    
# participants affected / at risk     3/3997 (0.08%)     1/4001 (0.02%)  
# events     3     1  
Duodenal ulcer perforation * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Dyspepsia * 1    
# participants affected / at risk     0/3997 (0.00%)     2/4001 (0.05%)  
# events     0     2  
Dysphagia * 1    
# participants affected / at risk     0/3997 (0.00%)     3/4001 (0.07%)  
# events     0     3  
Enteritis * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Enterocolitis * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Femoral hernia, obstructive * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Gastric haemorrhage * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Gastric ulcer * 1    
# participants affected / at risk     1/3997 (0.03%)     2/4001 (0.05%)  
# events     1     2  
Gastric ulcer haemorrhage * 1    
# participants affected / at risk     2/3997 (0.05%)     3/4001 (0.07%)  
# events     2     3  
Gastric ulcer perforation * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Gastritis * 1    
# participants affected / at risk     3/3997 (0.08%)     0/4001 (0.00%)  
# events     3     0  
Gastrooesophageal reflux disease * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Gastroduodenal ulcer * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Gastrointestinal haemorrhage * 1    
# participants affected / at risk     12/3997 (0.30%)     7/4001 (0.17%)  
# events     12     8  
Gastrointestinal perforation * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Gingival bleeding * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Haematemesis * 1    
# participants affected / at risk     3/3997 (0.08%)     4/4001 (0.10%)  
# events     3     4  
Haematochezia * 1    
# participants affected / at risk     4/3997 (0.10%)     1/4001 (0.02%)  
# events     4     1  
Ileus * 1    
# participants affected / at risk     6/3997 (0.15%)     0/4001 (0.00%)  
# events     6     0  
Ileus paralytic * 1    
# participants affected / at risk     2/3997 (0.05%)     0/4001 (0.00%)  
# events     2     0  
Impaired gastric emptying * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     2  
Inguinal hernia * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Intestinal infarction * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Intestinal ischaemia * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Intestinal obstruction * 1    
# participants affected / at risk     5/3997 (0.13%)     3/4001 (0.07%)  
# events     5     3  
Large intestinal ulcer * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Mallory-Weiss syndrome * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Melaena * 1    
# participants affected / at risk     6/3997 (0.15%)     3/4001 (0.07%)  
# events     6     3  
Mesenteric artery stenosis * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Mouth haemorrhage * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Nausea * 1    
# participants affected / at risk     3/3997 (0.08%)     5/4001 (0.12%)  
# events     3     7  
Oesophageal haemorrhage * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Oesophageal spasm * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Oesophageal stenosis * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Oesophageal ulcer * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Oesophageal varices haemorrhage * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Pancreatitis * 1    
# participants affected / at risk     0/3997 (0.00%)     2/4001 (0.05%)  
# events     0     2  
Pancreatitis acute * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Pancreatitis chronic * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Peritoneal haemorrhage * 1    
# participants affected / at risk     2/3997 (0.05%)     0/4001 (0.00%)  
# events     2     0  
Peritonitis * 1    
# participants affected / at risk     2/3997 (0.05%)     1/4001 (0.02%)  
# events     2     1  
Proctalgia * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Rectal haemorrhage * 1    
# participants affected / at risk     4/3997 (0.10%)     4/4001 (0.10%)  
# events     4     5  
Reflux oesophagitis * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Retroperitoneal haemorrhage * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Small intestinal obstruction * 1    
# participants affected / at risk     1/3997 (0.03%)     3/4001 (0.07%)  
# events     1     3  
Thrombosis mesenteric vessel * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Upper gastrointestinal haemorrhage * 1    
# participants affected / at risk     4/3997 (0.10%)     2/4001 (0.05%)  
# events     4     2  
Vomiting * 1    
# participants affected / at risk     7/3997 (0.18%)     4/4001 (0.10%)  
# events     7     5  
Oesophagitis ulcerative * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Anal haemorrhage * 1    
# participants affected / at risk     2/3997 (0.05%)     0/4001 (0.00%)  
# events     2     0  
Lower gastrointestinal haemorrhage * 1    
# participants affected / at risk     2/3997 (0.05%)     2/4001 (0.05%)  
# events     2     3  
Diabetic gastroparesis * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     2     0  
Internal hernia * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Oedematous pancreatitis * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Small intestinal haemorrhage * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Haemorrhoidal haemorrhage * 1    
# participants affected / at risk     1/3997 (0.03%)     2/4001 (0.05%)  
# events     1     2  
Varices oesophageal * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Hernial eventration * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Retroperitoneal haematoma * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Intestinal haemorrhage * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     2     0  
Abdominal hernia obstructive * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Diverticular perforation * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
General disorders      
Asthenia * 1    
# participants affected / at risk     4/3997 (0.10%)     1/4001 (0.02%)  
# events     4     1  
Chest pain * 1    
# participants affected / at risk     10/3997 (0.25%)     16/4001 (0.40%)  
# events     10     18  
Chills * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Death * 1    
# participants affected / at risk     14/3997 (0.35%)     9/4001 (0.22%)  
# events     14     9  
Fatigue * 1    
# participants affected / at risk     2/3997 (0.05%)     3/4001 (0.07%)  
# events     2     3  
Impaired healing * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Malaise * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Multi-organ failure * 1    
# participants affected / at risk     8/3997 (0.20%)     5/4001 (0.12%)  
# events     8     5  
Oedema * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Oedema peripheral * 1    
# participants affected / at risk     2/3997 (0.05%)     5/4001 (0.12%)  
# events     2     6  
Pain * 1    
# participants affected / at risk     4/3997 (0.10%)     2/4001 (0.05%)  
# events     4     3  
Pyrexia * 1    
# participants affected / at risk     8/3997 (0.20%)     9/4001 (0.22%)  
# events     8     9  
Sudden death * 1    
# participants affected / at risk     8/3997 (0.20%)     5/4001 (0.12%)  
# events     8     5  
Performance status decreased * 1    
# participants affected / at risk     0/3997 (0.00%)     2/4001 (0.05%)  
# events     0     3  
Hernia pain * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Sudden cardiac death * 1    
# participants affected / at risk     2/3997 (0.05%)     7/4001 (0.17%)  
# events     2     7  
General physical health deterioration * 1    
# participants affected / at risk     5/3997 (0.13%)     4/4001 (0.10%)  
# events     5     4  
Puncture site haemorrhage * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Nodule * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Catheter site haematoma * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Ulcer haemorrhage * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Drug intolerance * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Unevaluable event * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Non-cardiac chest pain * 1    
# participants affected / at risk     2/3997 (0.05%)     0/4001 (0.00%)  
# events     2     0  
Implant site haematoma * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Device malfunction * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Device dislocation * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Device occlusion * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Disuse syndrome * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Device capturing issue * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Hepatobiliary disorders      
Acute hepatic failure * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Biliary colic * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Cholecystitis * 1    
# participants affected / at risk     1/3997 (0.03%)     3/4001 (0.07%)  
# events     1     4  
Cholecystitis acute * 1    
# participants affected / at risk     2/3997 (0.05%)     2/4001 (0.05%)  
# events     2     2  
Cholelithiasis * 1    
# participants affected / at risk     2/3997 (0.05%)     4/4001 (0.10%)  
# events     2     4  
Cholestasis * 1    
# participants affected / at risk     2/3997 (0.05%)     0/4001 (0.00%)  
# events     2     0  
Granulomatous liver disease * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Hepatic cirrhosis * 1    
# participants affected / at risk     0/3997 (0.00%)     2/4001 (0.05%)  
# events     0     2  
Hepatic congestion * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Hepatic failure * 1    
# participants affected / at risk     1/3997 (0.03%)     2/4001 (0.05%)  
# events     1     2  
Hepatic function abnormal * 1    
# participants affected / at risk     7/3997 (0.18%)     5/4001 (0.12%)  
# events     7     5  
Hepatic steatosis * 1    
# participants affected / at risk     2/3997 (0.05%)     0/4001 (0.00%)  
# events     2     0  
Hepatitis acute * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Hepatitis alcoholic * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Hepatitis toxic * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Hepatorenal syndrome * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Hyperbilirubinaemia * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Ischaemic hepatitis * 1    
# participants affected / at risk     2/3997 (0.05%)     1/4001 (0.02%)  
# events     2     1  
Jaundice * 1    
# participants affected / at risk     2/3997 (0.05%)     0/4001 (0.00%)  
# events     2     0  
Cytolytic hepatitis * 1    
# participants affected / at risk     2/3997 (0.05%)     1/4001 (0.02%)  
# events     2     1  
Bile duct obstruction * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Haemobilia * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Hepatic lesion * 1    
# participants affected / at risk     0/3997 (0.00%)     2/4001 (0.05%)  
# events     0     2  
Cryptogenic cirrhosis * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Liver injury * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Immune system disorders      
Amyloidosis * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Anaphylactic reaction * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Drug hypersensitivity * 1    
# participants affected / at risk     0/3997 (0.00%)     2/4001 (0.05%)  
# events     0     2  
Hypersensitivity * 1    
# participants affected / at risk     0/3997 (0.00%)     2/4001 (0.05%)  
# events     0     2  
Sarcoidosis * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Infections and infestations      
Abscess * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Acquired immunodeficiency syndrome * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Appendicitis * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Appendicitis perforated * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Bacteraemia * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Bronchiectasis * 1    
# participants affected / at risk     3/3997 (0.08%)     2/4001 (0.05%)  
# events     3     2  
Bronchiolitis * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Bronchitis * 1    
# participants affected / at risk     18/3997 (0.45%)     4/4001 (0.10%)  
# events     18     4  
Bronchopneumonia * 1    
# participants affected / at risk     8/3997 (0.20%)     10/4001 (0.25%)  
# events     8     10  
Cellulitis * 1    
# participants affected / at risk     20/3997 (0.50%)     9/4001 (0.22%)  
# events     23     10  
Cellulitis streptococcal * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Diarrhoea infectious * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Disseminated tuberculosis * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Diverticulitis * 1    
# participants affected / at risk     5/3997 (0.13%)     1/4001 (0.02%)  
# events     5     1  
Empyema * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Endocarditis * 1    
# participants affected / at risk     1/3997 (0.03%)     2/4001 (0.05%)  
# events     1     3  
Enteritis necroticans * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Enterococcal bacteraemia * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Erysipelas * 1    
# participants affected / at risk     4/3997 (0.10%)     2/4001 (0.05%)  
# events     4     2  
Furuncle * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Gangrene * 1    
# participants affected / at risk     0/3997 (0.00%)     2/4001 (0.05%)  
# events     0     3  
Gastroenteritis * 1    
# participants affected / at risk     12/3997 (0.30%)     4/4001 (0.10%)  
# events     12     4  
Gastroenteritis viral * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Gastrointestinal infection * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Hepatitis C * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Herpes zoster * 1    
# participants affected / at risk     2/3997 (0.05%)     2/4001 (0.05%)  
# events     2     2  
Impetigo * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Infected skin ulcer * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Infection * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Liver abscess * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Lobar pneumonia * 1    
# participants affected / at risk     4/3997 (0.10%)     1/4001 (0.02%)  
# events     4     1  
Localised infection * 1    
# participants affected / at risk     3/3997 (0.08%)     0/4001 (0.00%)  
# events     3     0  
Lower respiratory tract infection * 1    
# participants affected / at risk     4/3997 (0.10%)     3/4001 (0.07%)  
# events     4     3  
Lung abscess * 1    
# participants affected / at risk     2/3997 (0.05%)     1/4001 (0.02%)  
# events     2     1  
Meningitis * 1    
# participants affected / at risk     0/3997 (0.00%)     2/4001 (0.05%)  
# events     0     2  
Necrotising fasciitis * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Oesophageal candidiasis * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Oral candidiasis * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Osteomyelitis * 1    
# participants affected / at risk     4/3997 (0.10%)     1/4001 (0.02%)  
# events     4     1  
Peridiverticular abscess * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Perinephric abscess * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Peritoneal abscess * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Pneumonia * 1    
# participants affected / at risk     74/3997 (1.85%)     76/4001 (1.90%)  
# events     78     78  
Pneumonia klebsiella * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Pneumonia pneumococcal * 1    
# participants affected / at risk     2/3997 (0.05%)     0/4001 (0.00%)  
# events     2     0  
Pneumonia primary atypical * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Postoperative wound infection * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Pseudomembranous colitis * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Pulmonary tuberculosis * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Pyelonephritis * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Pyelonephritis acute * 1    
# participants affected / at risk     1/3997 (0.03%)     2/4001 (0.05%)  
# events     1     2  
Pyometra * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Pyothorax * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Retroperitoneal abscess * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Salmonellosis * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Sepsis * 1    
# participants affected / at risk     29/3997 (0.73%)     14/4001 (0.35%)  
# events     30     14  
Septic shock * 1    
# participants affected / at risk     15/3997 (0.38%)     18/4001 (0.45%)  
# events     16     20  
Sinusitis * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Subcutaneous abscess * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Tuberculosis * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     2     0  
Upper respiratory tract infection * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Urinary tract infection * 1    
# participants affected / at risk     17/3997 (0.43%)     13/4001 (0.32%)  
# events     20     14  
Viral infection * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Viral upper respiratory tract infection * 1    
# participants affected / at risk     0/3997 (0.00%)     2/4001 (0.05%)  
# events     0     2  
Wound infection * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Urosepsis * 1    
# participants affected / at risk     4/3997 (0.10%)     6/4001 (0.15%)  
# events     4     6  
Abscess limb * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Staphylococcal bacteraemia * 1    
# participants affected / at risk     2/3997 (0.05%)     0/4001 (0.00%)  
# events     2     0  
Burn infection * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Haematoma infection * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Pulmonary sepsis * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Bacterial sepsis * 1    
# participants affected / at risk     1/3997 (0.03%)     2/4001 (0.05%)  
# events     1     2  
Sepsis syndrome * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Psoas abscess * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Phlebitis infective * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Infective exacerbation of chronic obstructive airways disease * 1    
# participants affected / at risk     10/3997 (0.25%)     12/4001 (0.30%)  
# events     10     12  
Lung infection pseudomonal * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Abdominal sepsis * 1    
# participants affected / at risk     3/3997 (0.08%)     0/4001 (0.00%)  
# events     3     0  
Wound sepsis * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Staphylococcal infection * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Tuberculosis liver * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Enterocolitis infectious * 1    
# participants affected / at risk     2/3997 (0.05%)     0/4001 (0.00%)  
# events     2     0  
Wound infection staphylococcal * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Implant site infection * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Intervertebral discitis * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     2     0  
Diabetic foot infection * 1    
# participants affected / at risk     1/3997 (0.03%)     2/4001 (0.05%)  
# events     1     2  
Abdominal abscess * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Pneumonia bacterial * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Arthritis infective * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Lung infection * 1    
# participants affected / at risk     2/3997 (0.05%)     4/4001 (0.10%)  
# events     2     4  
Pneumonia fungal * 1    
# participants affected / at risk     2/3997 (0.05%)     1/4001 (0.02%)  
# events     2     1  
Bronchitis bacterial * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Respiratory tract infection * 1    
# participants affected / at risk     10/3997 (0.25%)     6/4001 (0.15%)  
# events     12     6  
Cholecystitis infective * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Infective spondylitis * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Device related infection * 1    
# participants affected / at risk     2/3997 (0.05%)     2/4001 (0.05%)  
# events     2     2  
Staphylococcal skin infection * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Post procedural infection * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
H1N1 influenza * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Device related sepsis * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Injury, poisoning and procedural complications      
Alcohol poisoning * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Ankle fracture * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Burns second degree * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Clavicle fracture * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Drug toxicity * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Eye penetration * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Fall * 1    
# participants affected / at risk     5/3997 (0.13%)     3/4001 (0.07%)  
# events     5     3  
Femoral neck fracture * 1    
# participants affected / at risk     2/3997 (0.05%)     4/4001 (0.10%)  
# events     2     4  
Femur fracture * 1    
# participants affected / at risk     2/3997 (0.05%)     3/4001 (0.07%)  
# events     2     3  
Foot fracture * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Head injury * 1    
# participants affected / at risk     1/3997 (0.03%)     2/4001 (0.05%)  
# events     1     2  
Hip fracture * 1    
# participants affected / at risk     5/3997 (0.13%)     0/4001 (0.00%)  
# events     5     0  
Humerus fracture * 1    
# participants affected / at risk     4/3997 (0.10%)     2/4001 (0.05%)  
# events     4     2  
Incisional hernia, obstructive * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Operative haemorrhage * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Overdose * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Periorbital haematoma * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Pneumoconiosis * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Radius fracture * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Rib fracture * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Spinal compression fracture * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Spinal cord injury cervical * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Spinal fracture * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Subdural haematoma * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Subdural haemorrhage * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Therapeutic agent toxicity * 1    
# participants affected / at risk     0/3997 (0.00%)     2/4001 (0.05%)  
# events     0     2  
Tibia fracture * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Wound dehiscence * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Suture rupture * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Vascular graft occlusion * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Traumatic fracture * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Cervical vertebral fracture * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Lumbar vertebral fracture * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Contusion * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Post procedural haemorrhage * 1    
# participants affected / at risk     4/3997 (0.10%)     1/4001 (0.02%)  
# events     4     1  
Wound * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Traumatic haemorrhage * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Exposure to toxic agent * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Thermal burn * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Wound necrosis * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Multiple drug overdose * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Poisoning * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Chest injury * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Upper limb fracture * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Procedural pain * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Gastrointestinal stoma complication * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Procedural nausea * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Foreign body * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Investigations      
Alanine aminotransferase increased * 1    
# participants affected / at risk     20/3997 (0.50%)     23/4001 (0.57%)  
# events     20     26  
Arteriogram coronary * 1    
# participants affected / at risk     1/3997 (0.03%)     2/4001 (0.05%)  
# events     1     2  
Aspartate aminotransferase increased * 1    
# participants affected / at risk     1/3997 (0.03%)     5/4001 (0.12%)  
# events     1     7  
Biopsy lymph gland * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Blood bilirubin increased * 1    
# participants affected / at risk     4/3997 (0.10%)     1/4001 (0.02%)  
# events     4     1  
Blood creatinine increased * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Blood glucose abnormal * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Blood glucose decreased * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Blood glucose increased * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     2     0  
Creatinine renal clearance decreased * 1    
# participants affected / at risk     4/3997 (0.10%)     3/4001 (0.07%)  
# events     4     3  
Gamma-glutamyltransferase increased * 1    
# participants affected / at risk     1/3997 (0.03%)     1/4001 (0.02%)  
# events     1     1  
Haemoglobin decreased * 1    
# participants affected / at risk     2/3997 (0.05%)     1/4001 (0.02%)  
# events     3     1  
Immunoglobulins increased * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Liver function test abnormal * 1    
# participants affected / at risk     8/3997 (0.20%)     5/4001 (0.12%)  
# events     8     5  
Prothrombin time prolonged * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Weight decreased * 1    
# participants affected / at risk     2/3997 (0.05%)     0/4001 (0.00%)  
# events     2     0  
Aspiration bronchial * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Transaminases increased * 1    
# participants affected / at risk     3/3997 (0.08%)     2/4001 (0.05%)  
# events     3     2  
Blood alkaline phosphatase increased * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Hepatic enzyme increased * 1    
# participants affected / at risk     10/3997 (0.25%)     11/4001 (0.27%)  
# events     10     11  
Occult blood positive * 1    
# participants affected / at risk     1/3997 (0.03%)     2/4001 (0.05%)  
# events     1     2  
Coagulation test * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
False positive investigation result * 1    
# participants affected / at risk     1/3997 (0.03%)     0/4001 (0.00%)  
# events     1     0  
Metabolism and nutrition disorders      
Abnormal loss of weight * 1    
# participants affected / at risk     0/3997 (0.00%)     1/4001 (0.02%)  
# events     0     1  
Cachexia * 1    
# participants affected / at risk     2/3997 (0.05%)