ClinicalTrials.gov
ClinicalTrials.gov Menu

A Phase III Study of Apixaban in Patients With Atrial Fibrillation (AVERROES)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00496769
Recruitment Status : Completed
First Posted : July 4, 2007
Results First Posted : November 14, 2013
Last Update Posted : June 15, 2018
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition: Atrial Fibrillation
Interventions: Drug: Apixaban
Drug: Acetylsalicylic acid

  Participant Flow

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
A total 6421 patients were enrolled in the study. Of these, 5598 were randomized (2807 to apixaban and 2791 to acetylsalicylic acid). Most (435) of the patients who were not randomized (823) no longer met study criteria. Of those randomized, 5578 received treatment (2798 with apixaban, and 2780 with acetylsalicylic acid).

Reporting Groups
  Description
Apixaban, 2.5 or 5 mg Twice Daily Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.
Acetylsalicylic Acid, 81-324 mg Once Daily Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.
Open Label Apixaban Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Participant Flow for 2 periods

Period 1:   Double Blind
    Apixaban, 2.5 or 5 mg Twice Daily   Acetylsalicylic Acid, 81-324 mg Once Daily   Open Label Apixaban
STARTED   2807 [1]   2791 [1]   0 
Received Treatment   2798   2708   0 
COMPLETED   2249   2142   0 
NOT COMPLETED   558   649   0 
>=1 reason assigned per patient                558                649                0 
[1] Randomized

Period 2:   Open Label
    Apixaban, 2.5 or 5 mg Twice Daily   Acetylsalicylic Acid, 81-324 mg Once Daily   Open Label Apixaban
STARTED   0   0   3275 
COMPLETED   0   0   2264 
NOT COMPLETED   0   0   1011 
>=1 reason assigned per patient                0                0                1011 



  Baseline Characteristics

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
Apixaban, 2.5 or 5 mg Twice Daily Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.
Acetylsalicylic Acid, 81-324 mg Once Daily Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion
Total Total of all reporting groups

Baseline Measures
   Apixaban, 2.5 or 5 mg Twice Daily   Acetylsalicylic Acid, 81-324 mg Once Daily   Total 
Overall Participants Analyzed 
[Units: Participants]
 2807   2791   5598 
Age 
[Units: Years]
Mean (Standard Deviation)
 69.7  (9.44)   70.0  (9.71)   69.9  (9.58) 
Age, Customized 
[Units: Participants]
Count of Participants
     
< 65 years      855  30.5%      865  31.0%      1720  30.7% 
>=65 but <75 years      1049  37.4%      938  33.6%      1987  35.5% 
>=75 years      903  32.2%      988  35.4%      1891  33.8% 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      1147  40.9%      1174  42.1%      2321  41.5% 
Male      1660  59.1%      1617  57.9%      3277  58.5% 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
     
American Indian or Alaska Native      6   0.2%      6   0.2%      12   0.2% 
Asian      541  19.3%      544  19.5%      1085  19.4% 
Native Hawaiian or Other Pacific Islander      3   0.1%      1   0.0%      4   0.1% 
Black or African American      10   0.4%      26   0.9%      36   0.6% 
White      2221  79.1%      2178  78.0%      4399  78.6% 
Other      26   0.9%      36   1.3%      62   1.1% 
Number of Participants by Number of Risk Factors for Stroke 
[Units: Participants]
Count of Participants
     
1 or fewer      1085  38.7%      1077  38.6%      2162  38.6% 
2 or more      1722  61.3%      1714  61.4%      3436  61.4% 
Number of Participants With Risk Factors for Stroke [1] 
[Units: Participants]
Count of Participants
     
Age of 75 years or older   903   988   1891 
Prior stroke or transient ischemic attack   390   374   764 
Heart failure (NYHA class ≥2) or LVEF ≤35%   961   926   1887 
Diabetes mellitus   536   559   1095 
Hypertension requiring pharmacologic treatment   2408   2429   4837 
Peripheral artery disease   66   78   144 
[1] NYHA=New York Health Authority; LVEF=left ventricular ejection fraction


  Outcome Measures

1.  Primary:   Event Rate of Stroke/Systemic Embolism During the Intended-treatment Period   [ Time Frame: Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy) ]

2.  Secondary:   Event Rate for the Composite of Stroke of Any Type, Systemic Embolism, Myocardial Infarction, or Vascular Death During the Double-blind Treatment Period   [ Time Frame: Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy) ]

3.  Secondary:   Event Rate of All-cause Death; Net Clinical Benefit-Composite of Stroke, Systemic Embolism, Myocardial Infarction, Vascular Death, and Major Bleeding; and Vascular Death   [ Time Frame: Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy) ]

4.  Secondary:   Event Rates for Major Bleeding, Major or Clinically Relevant Nonmajor (CNRM) Bleeding, and All Bleeding in the Double-blind Period   [ Time Frame: First dose of study drug (Day 1) to the earlier of a patient's discontinuation of double-blind study drug or the attainment of at least 226 primary efficacy events up to May 28, 2010 ]

5.  Secondary:   Rate of Unrefuted Bleeding From First Dose of Double-blind Study Drug to First Occurence of Unrefuted Bleeding During the Double-blind Treatment Period   [ Time Frame: Day 1 to first bleeding event up to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy) ]

6.  Secondary:   Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome   [ Time Frame: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug ]

7.  Secondary:   Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality   [ Time Frame: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug ]

8.  Secondary:   Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued)   [ Time Frame: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug ]

9.  Secondary:   Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued)   [ Time Frame: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug ]


  Serious Adverse Events

Time Frame From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Additional Description No text entered.

Reporting Groups
  Description
Apixaban, 2.5 or 5 mg Twice Daily Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.
Acetylsalicylic Acid, 81-324 mg Once Daily

Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion

Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Open Label Apixaban Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.

Serious Adverse Events
    Apixaban, 2.5 or 5 mg Twice Daily   Acetylsalicylic Acid, 81-324 mg Once Daily   Open Label Apixaban
Total, All-Cause Mortality       
# participants affected / at risk   111/2798 (3.97%)   140/2780 (5.04%)   286/3275 (8.73%) 
Total, Serious Adverse Events       
# participants affected / at risk   657/2798 (23.48%)   804/2780 (28.92%)   1228/3275 (37.50%) 
Blood and lymphatic system disorders       
Anaemia † 1       
# participants affected / at risk   12/2798 (0.43%)   11/2780 (0.40%)   23/3275 (0.70%) 
Lymphadenopathy † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Thrombocytopenia † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   1/3275 (0.03%) 
Aplastic anaemia † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Coagulopathy † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Haemorrhagic diathesis † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Iron deficiency anaemia † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   3/3275 (0.09%) 
Leukocytosis † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Anaemia megaloblastic † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Haemolytic anaemia † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Leukopenia † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Pancytopenia † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Cardiac disorders       
Acute myocardial infarction † 1       
# participants affected / at risk   11/2798 (0.39%)   19/2780 (0.68%)   25/3275 (0.76%) 
Atrial flutter † 1       
# participants affected / at risk   7/2798 (0.25%)   6/2780 (0.22%)   8/3275 (0.24%) 
Cardiac failure † 1       
# participants affected / at risk   60/2798 (2.14%)   76/2780 (2.73%)   116/3275 (3.54%) 
Cardiogenic shock † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   5/3275 (0.15%) 
Palpitations † 1       
# participants affected / at risk   4/2798 (0.14%)   2/2780 (0.07%)   2/3275 (0.06%) 
Pericardial effusion † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   2/3275 (0.06%) 
Atrioventricular block † 1       
# participants affected / at risk   1/2798 (0.04%)   2/2780 (0.07%)   3/3275 (0.09%) 
Bradycardia † 1       
# participants affected / at risk   5/2798 (0.18%)   4/2780 (0.14%)   11/3275 (0.34%) 
Conduction disorder † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Left ventricular dysfunction † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   3/3275 (0.09%) 
Mitral valve prolapse † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Ventricular failure † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Atrial fibrillation † 1       
# participants affected / at risk   72/2798 (2.57%)   70/2780 (2.52%)   113/3275 (3.45%) 
Cardio-respiratory arrest † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   7/3275 (0.21%) 
Cardiovascular insufficiency † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Myocardial ischaemia † 1       
# participants affected / at risk   3/2798 (0.11%)   2/2780 (0.07%)   4/3275 (0.12%) 
Sinoatrial block † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Supraventricular tachycardia † 1       
# participants affected / at risk   3/2798 (0.11%)   5/2780 (0.18%)   1/3275 (0.03%) 
Tachyarrhythmia † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   0/3275 (0.00%) 
Acute coronary syndrome † 1       
# participants affected / at risk   3/2798 (0.11%)   6/2780 (0.22%)   7/3275 (0.21%) 
Arrhythmia supraventricular † 1       
# participants affected / at risk   1/2798 (0.04%)   2/2780 (0.07%)   0/3275 (0.00%) 
Atrial tachycardia † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   2/3275 (0.06%) 
Cardiopulmonary failure † 1       
# participants affected / at risk   2/2798 (0.07%)   3/2780 (0.11%)   4/3275 (0.12%) 
Carditis † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Coronary artery disease † 1       
# participants affected / at risk   4/2798 (0.14%)   6/2780 (0.22%)   16/3275 (0.49%) 
Coronary artery insufficiency † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Intracardiac thrombus † 1       
# participants affected / at risk   3/2798 (0.11%)   3/2780 (0.11%)   0/3275 (0.00%) 
Sick sinus syndrome † 1       
# participants affected / at risk   8/2798 (0.29%)   11/2780 (0.40%)   0/3275 (0.00%) 
Ventricular tachycardia † 1       
# participants affected / at risk   3/2798 (0.11%)   3/2780 (0.11%)   4/3275 (0.12%) 
Angina unstable † 1       
# participants affected / at risk   20/2798 (0.71%)   12/2780 (0.43%)   17/3275 (0.52%) 
Atrioventricular block complete † 1       
# participants affected / at risk   3/2798 (0.11%)   2/2780 (0.07%)   1/3275 (0.03%) 
Cardiac failure congestive † 1       
# participants affected / at risk   39/2798 (1.39%)   28/2780 (1.01%)   53/3275 (1.62%) 
Cardiomyopathy † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   1/3275 (0.03%) 
Ischaemic cardiomyopathy † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   3/3275 (0.09%) 
Tachycardia † 1       
# participants affected / at risk   1/2798 (0.04%)   2/2780 (0.07%)   2/3275 (0.06%) 
Tricuspid valve incompetence † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Ventricular arrhythmia † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   4/3275 (0.12%) 
Ventricular fibrillation † 1       
# participants affected / at risk   1/2798 (0.04%)   2/2780 (0.07%)   3/3275 (0.09%) 
Arrhythmia † 1       
# participants affected / at risk   0/2798 (0.00%)   2/2780 (0.07%)   4/3275 (0.12%) 
Nodal arrhythmia † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Sinus arrhythmia † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Sinus bradycardia † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   1/3275 (0.03%) 
Angina pectoris † 1       
# participants affected / at risk   4/2798 (0.14%)   9/2780 (0.32%)   14/3275 (0.43%) 
Bradyarrhythmia † 1       
# participants affected / at risk   2/2798 (0.07%)   1/2780 (0.04%)   3/3275 (0.09%) 
Cardiac arrest † 1       
# participants affected / at risk   3/2798 (0.11%)   7/2780 (0.25%)   10/3275 (0.31%) 
Cardiac failure chronic † 1       
# participants affected / at risk   0/2798 (0.00%)   3/2780 (0.11%)   6/3275 (0.18%) 
Cor pulmonale † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Mitral valve incompetence † 1       
# participants affected / at risk   1/2798 (0.04%)   3/2780 (0.11%)   5/3275 (0.15%) 
Myocardial infarction † 1       
# participants affected / at risk   11/2798 (0.39%)   12/2780 (0.43%)   24/3275 (0.73%) 
Aortic valve incompetence † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Cardiac failure acute † 1       
# participants affected / at risk   3/2798 (0.11%)   7/2780 (0.25%)   3/3275 (0.09%) 
Coronary artery occlusion † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Left ventricular failure † 1       
# participants affected / at risk   0/2798 (0.00%)   3/2780 (0.11%)   6/3275 (0.18%) 
Microvascular angina † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Right ventricular failure † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Acute left ventricular failure † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Aortic valve stenosis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Arteriosclerosis coronary artery † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Cardiac asthma † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Cardiac disorder † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Congestive cardiomyopathy † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   3/3275 (0.09%) 
Defect conduction intraventricular † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Hypertensive heart disease † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Mitral valve disease † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Mitral valve stenosis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   4/3275 (0.12%) 
Nodal rhythm † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Pericarditis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Pericarditis constrictive † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Prinzmetal angina † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Rheumatic heart disease † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Sinus arrest † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Sinus node dysfunction † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   18/3275 (0.55%) 
Ventricular extrasystoles † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Congenital, familial and genetic disorders       
Atrial septal defect † 1       
# participants affected / at risk   0/2798 (0.00%)   2/2780 (0.07%)   0/3275 (0.00%) 
Congenital cystic kidney disease † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Liddle's syndrome † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Ear and labyrinth disorders       
Ear disorder † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Vertigo † 1       
# participants affected / at risk   1/2798 (0.04%)   3/2780 (0.11%)   5/3275 (0.15%) 
Vertigo positional † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Ear haemorrhage † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Endocrine disorders       
Hyperparathyroidism † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Hyperthyroidism † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   4/3275 (0.12%) 
Thyroid haemorrhage † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Hypothyroidism † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Goitre † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Thyroid mass † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Eye disorders       
Eye haemorrhage † 1       
# participants affected / at risk   2/2798 (0.07%)   0/2780 (0.00%)   0/3275 (0.00%) 
Vitreous haemorrhage † 1       
# participants affected / at risk   2/2798 (0.07%)   0/2780 (0.00%)   0/3275 (0.00%) 
Retinal artery occlusion † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Retinal detachment † 1       
# participants affected / at risk   0/2798 (0.00%)   2/2780 (0.07%)   0/3275 (0.00%) 
Amaurosis fugax † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Retinal artery embolism † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Cataract † 1       
# participants affected / at risk   2/2798 (0.07%)   0/2780 (0.00%)   6/3275 (0.18%) 
Eye pain † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Eyelid ptosis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Keratitis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Tolosa-hunt syndrome † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Gastrointestinal disorders       
Abdominal pain upper † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   0/3275 (0.00%) 
Diverticulum † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   2/3275 (0.06%) 
Gastroduodenitis † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Haematochezia † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Intestinal ischaemia † 1       
# participants affected / at risk   0/2798 (0.00%)   2/2780 (0.07%)   0/3275 (0.00%) 
Pancreatitis chronic † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   0/3275 (0.00%) 
Abdominal hernia † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   2/3275 (0.06%) 
Colitis † 1       
# participants affected / at risk   2/2798 (0.07%)   0/2780 (0.00%)   1/3275 (0.03%) 
Duodenal ulcer † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   3/3275 (0.09%) 
Gastric disorder † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Gastritis † 1       
# participants affected / at risk   5/2798 (0.18%)   6/2780 (0.22%)   3/3275 (0.09%) 
Gastritis erosive † 1       
# participants affected / at risk   1/2798 (0.04%)   2/2780 (0.07%)   2/3275 (0.06%) 
Haematemesis † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   4/3275 (0.12%) 
Intestinal obstruction † 1       
# participants affected / at risk   1/2798 (0.04%)   2/2780 (0.07%)   6/3275 (0.18%) 
Lumbar hernia † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Mouth haemorrhage † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Peptic ulcer † 1       
# participants affected / at risk   1/2798 (0.04%)   2/2780 (0.07%)   1/3275 (0.03%) 
Retroperitoneal haematoma † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Colonic polyp † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Dyspepsia † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Dysphagia † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Gastrooesophageal reflux disease † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Gingival bleeding † 1       
# participants affected / at risk   2/2798 (0.07%)   1/2780 (0.04%)   0/3275 (0.00%) 
Mesenteric artery embolism † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Oesophageal achalasia † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Rectal haemorrhage † 1       
# participants affected / at risk   7/2798 (0.25%)   1/2780 (0.04%)   8/3275 (0.24%) 
Reflux oesophagitis † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Subileus † 1       
# participants affected / at risk   2/2798 (0.07%)   0/2780 (0.00%)   0/3275 (0.00%) 
Gastric ulcer haemorrhage † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   2/3275 (0.06%) 
Gastrointestinal haemorrhage † 1       
# participants affected / at risk   2/2798 (0.07%)   9/2780 (0.32%)   20/3275 (0.61%) 
Gastrointestinal hypomotility † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Ileus † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Oesophagitis † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Pancreatitis acute † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   3/3275 (0.09%) 
Proctitis ulcerative † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Duodenal ulcer haemorrhage † 1       
# participants affected / at risk   2/2798 (0.07%)   0/2780 (0.00%)   1/3275 (0.03%) 
Duodenitis † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   0/3275 (0.00%) 
Gastric haemorrhage † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Gastrointestinal disorder † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Intestinal haemorrhage † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Large intestinal obstruction † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Melaena † 1       
# participants affected / at risk   5/2798 (0.18%)   1/2780 (0.04%)   5/3275 (0.15%) 
Oesophageal varices haemorrhage † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Spigelian hernia † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Abdominal adhesions † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Constipation † 1       
# participants affected / at risk   1/2798 (0.04%)   2/2780 (0.07%)   6/3275 (0.18%) 
Food poisoning † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   2/3275 (0.06%) 
Gastric ulcer † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   4/3275 (0.12%) 
Gastrointestinal perforation † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Mesenteric artery thrombosis † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Nausea † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Abdominal pain † 1       
# participants affected / at risk   4/2798 (0.14%)   3/2780 (0.11%)   6/3275 (0.18%) 
Diarrhoea † 1       
# participants affected / at risk   0/2798 (0.00%)   5/2780 (0.18%)   11/3275 (0.34%) 
Faecaloma † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   2/3275 (0.06%) 
Inguinal hernia † 1       
# participants affected / at risk   3/2798 (0.11%)   6/2780 (0.22%)   12/3275 (0.37%) 
Oesophageal stenosis † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Pancreatitis † 1       
# participants affected / at risk   2/2798 (0.07%)   3/2780 (0.11%)   2/3275 (0.06%) 
Small intestinal obstruction † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   2/3275 (0.06%) 
Abdominal strangulated hernia † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Acute abdomen † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Duodenal ulcer perforation † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Gastritis haemorrhagic † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Hiatus hernia † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Splenic artery aneurysm † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Tooth loss † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Vomiting † 1       
# participants affected / at risk   2/2798 (0.07%)   1/2780 (0.04%)   1/3275 (0.03%) 
Abdominal distension † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Abdominal mass † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Abdominal wall haematoma † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Ascites † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   3/3275 (0.09%) 
Barrett's oesophagus † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Chronic gastritis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Colitis ulcerative † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Diverticulum intestinal † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Haemorrhoidal haemorrhage † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   3/3275 (0.09%) 
Haemorrhoids † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   3/3275 (0.09%) 
Ileus paralytic † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Incarcerated umbilical hernia † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Large intestine perforation † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Large intestine polyp † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   3/3275 (0.09%) 
Lower gastrointestinal haemorrhage † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Mallory-weiss syndrome † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Oesophageal dilatation † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Proctitis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Umbilical hernia † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Upper gastrointestinal haemorrhage † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   14/3275 (0.43%) 
Volvulus † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
General disorders       
Chest pain † 1       
# participants affected / at risk   16/2798 (0.57%)   24/2780 (0.86%)   28/3275 (0.85%) 
Gait disturbance † 1       
# participants affected / at risk   0/2798 (0.00%)   2/2780 (0.07%)   1/3275 (0.03%) 
Malaise † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Pain † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Device pacing issue † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Implant site effusion † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Device lead damage † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Generalised oedema † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   1/3275 (0.03%) 
Hernia pain † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Sudden cardiac death † 1       
# participants affected / at risk   3/2798 (0.11%)   1/2780 (0.04%)   6/3275 (0.18%) 
Asthenia † 1       
# participants affected / at risk   4/2798 (0.14%)   1/2780 (0.04%)   9/3275 (0.27%) 
Cardiac death † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   3/3275 (0.09%) 
General physical health deterioration † 1       
# participants affected / at risk   3/2798 (0.11%)   1/2780 (0.04%)   1/3275 (0.03%) 
Medical device complication † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Oedema peripheral † 1       
# participants affected / at risk   2/2798 (0.07%)   1/2780 (0.04%)   7/3275 (0.21%) 
Systemic inflammatory response syndrome † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   1/3275 (0.03%) 
Adverse drug reaction † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   3/3275 (0.09%) 
Chest discomfort † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   2/3275 (0.06%) 
Device malfunction † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Pelvic mass † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Fatigue † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Hernia † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Multi-organ failure † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Oedema † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Pyrexia † 1       
# participants affected / at risk   3/2798 (0.11%)   3/2780 (0.11%)   7/3275 (0.21%) 
Death † 1       
# participants affected / at risk   14/2798 (0.50%)   9/2780 (0.32%)   38/3275 (1.16%) 
Non-cardiac chest pain † 1       
# participants affected / at risk   3/2798 (0.11%)   5/2780 (0.18%)   2/3275 (0.06%) 
Sudden death † 1       
# participants affected / at risk   9/2798 (0.32%)   12/2780 (0.43%)   32/3275 (0.98%) 
Swelling † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Unassigned † 1       
# participants affected / at risk   4/2798 (0.14%)   6/2780 (0.22%)   7/3275 (0.21%) 
Exercise tolerance decreased † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Incarcerated hernia † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Multiple organ dysfunction syndrome † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   5/3275 (0.15%) 
Peripheral swelling † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Unevaluable event † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Hepatobiliary disorders       
Cholecystitis † 1       
# participants affected / at risk   5/2798 (0.18%)   6/2780 (0.22%)   4/3275 (0.12%) 
Bile duct stone † 1       
# participants affected / at risk   1/2798 (0.04%)   3/2780 (0.11%)   3/3275 (0.09%) 
Cholestasis † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Hepatitis † 1       
# participants affected / at risk   2/2798 (0.07%)   0/2780 (0.00%)   0/3275 (0.00%) 
Cholecystitis chronic † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Hepatic failure † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Jaundice cholestatic † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Cholelithiasis † 1       
# participants affected / at risk   3/2798 (0.11%)   2/2780 (0.07%)   7/3275 (0.21%) 
Bile duct stenosis † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Cholangitis † 1       
# participants affected / at risk   2/2798 (0.07%)   0/2780 (0.00%)   3/3275 (0.09%) 
Cholecystitis acute † 1       
# participants affected / at risk   5/2798 (0.18%)   2/2780 (0.07%)   4/3275 (0.12%) 
Hyperbilirubinaemia † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Liver disorder † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Acute hepatic failure † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Cholangitis acute † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Hepatic cirrhosis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Hepatic cyst † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Hepatitis fulminant † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Hepatomegaly † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Portal hypertension † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Immune system disorders       
Anaphylactic reaction † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Infections and infestations       
Abdominal wall abscess † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Bronchitis † 1       
# participants affected / at risk   7/2798 (0.25%)   7/2780 (0.25%)   15/3275 (0.46%) 
Chronic sinusitis † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Dengue fever † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Hepatitis C † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Infection † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Infective exacerbation of chronic obstructive airways disease † 1       
# participants affected / at risk   1/2798 (0.04%)   2/2780 (0.07%)   1/3275 (0.03%) 
Lobar pneumonia † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   0/3275 (0.00%) 
Postoperative wound infection † 1       
# participants affected / at risk   1/2798 (0.04%)   2/2780 (0.07%)   2/3275 (0.06%) 
Septic shock † 1       
# participants affected / at risk   4/2798 (0.14%)   2/2780 (0.07%)   12/3275 (0.37%) 
Wound infection † 1       
# participants affected / at risk   2/2798 (0.07%)   0/2780 (0.00%)   1/3275 (0.03%) 
Bronchopneumonia † 1       
# participants affected / at risk   2/2798 (0.07%)   5/2780 (0.18%)   0/3275 (0.00%) 
Helicobacter gastritis † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Hepatic amoebiasis † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Influenza † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Meningitis † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Skin infection † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Tracheitis † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Vestibular neuronitis † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   0/3275 (0.00%) 
Abscess † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Abscess limb † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   2/3275 (0.06%) 
Amoebic dysentery † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Lung infection † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   2/3275 (0.06%) 
Psoas abscess † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Staphylococcal sepsis † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Viral infection † 1       
# participants affected / at risk   1/2798 (0.04%)   3/2780 (0.11%)   0/3275 (0.00%) 
Arthritis bacterial † 1       
# participants affected / at risk   2/2798 (0.07%)   0/2780 (0.00%)   0/3275 (0.00%) 
Endocarditis † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   3/3275 (0.09%) 
Escherichia bacteraemia † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Gastroenteritis † 1       
# participants affected / at risk   8/2798 (0.29%)   5/2780 (0.18%)   14/3275 (0.43%) 
Klebsiella bacteraemia † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Lower respiratory tract infection † 1       
# participants affected / at risk   2/2798 (0.07%)   2/2780 (0.07%)   5/3275 (0.15%) 
Osteomyelitis † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Pneumonia † 1       
# participants affected / at risk   37/2798 (1.32%)   55/2780 (1.98%)   99/3275 (3.02%) 
Pneumonia klebsiella † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Pneumonia pneumococcal † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Pyelonephritis † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   2/3275 (0.06%) 
Pyometra † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Cellulitis † 1       
# participants affected / at risk   6/2798 (0.21%)   5/2780 (0.18%)   13/3275 (0.40%) 
Clostridium colitis † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Diverticulitis † 1       
# participants affected / at risk   0/2798 (0.00%)   3/2780 (0.11%)   7/3275 (0.21%) 
Gangrene † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Localised infection † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   2/3275 (0.06%) 
Pneumonia viral † 1       
# participants affected / at risk   0/2798 (0.00%)   2/2780 (0.07%)   0/3275 (0.00%) 
Respiratory tract infection † 1       
# participants affected / at risk   3/2798 (0.11%)   5/2780 (0.18%)   6/3275 (0.18%) 
Sepsis † 1       
# participants affected / at risk   4/2798 (0.14%)   4/2780 (0.14%)   17/3275 (0.52%) 
Sinusitis † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Urinary tract infection † 1       
# participants affected / at risk   11/2798 (0.39%)   15/2780 (0.54%)   24/3275 (0.73%) 
Bronchiectasis † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Clostridium difficile colitis † 1       
# participants affected / at risk   0/2798 (0.00%)   2/2780 (0.07%)   1/3275 (0.03%) 
Gastroenteritis salmonella † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Herpes zoster † 1       
# participants affected / at risk   0/2798 (0.00%)   2/2780 (0.07%)   3/3275 (0.09%) 
Pyelonephritis acute † 1       
# participants affected / at risk   1/2798 (0.04%)   2/2780 (0.07%)   1/3275 (0.03%) 
Upper respiratory tract infection † 1       
# participants affected / at risk   3/2798 (0.11%)   1/2780 (0.04%)   3/3275 (0.09%) 
Urosepsis † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   4/3275 (0.12%) 
Appendicitis † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   6/3275 (0.18%) 
Helicobacter infection † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Oral candidiasis † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Urinary tract infection bacterial † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Abdominal wall infection † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Colonic abscess † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Cystitis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Diabetic foot infection † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Disseminated tuberculosis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Diverticulitis intestinal haemorrhagic † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Empyema † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Encephalitis viral † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Endophthalmitis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Erysipelas † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   8/3275 (0.24%) 
Escherichia infection † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Gastroenteritis viral † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   3/3275 (0.09%) 
Gastrointestinal infection † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Groin infection † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Hepatitis E † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Infectious pleural effusion † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Listeriosis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Liver abscess † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Nasopharyngitis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Nosocomial infection † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Oesophageal candidiasis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Ophthalmic herpes zoster † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Orchitis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Periorbital cellulitis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Peritonitis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Pneumonia escherichia † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Pneumonia influenzal † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Prostate infection † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Pulmonary tuberculosis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Sepsis syndrome † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Staphylococcal infection † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Tracheobronchitis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Tuberculosis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Tuberculous pleurisy † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Viral upper respiratory tract infection † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Injury, poisoning and procedural complications       
Concussion † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   0/3275 (0.00%) 
Hand fracture † 1       
# participants affected / at risk   2/2798 (0.07%)   0/2780 (0.00%)   0/3275 (0.00%) 
Multiple fractures † 1       
# participants affected / at risk   2/2798 (0.07%)   0/2780 (0.00%)   2/3275 (0.06%) 
Skull fracture † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Traumatic brain injury † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Upper limb fracture † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   4/3275 (0.12%) 
Cerebral haemorrhage traumatic † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Drug toxicity † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Foot fracture † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Joint dislocation † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Limb traumatic amputation † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Lumbar vertebral fracture † 1       
# participants affected / at risk   1/2798 (0.04%)   2/2780 (0.07%)   7/3275 (0.21%) 
Muscle strain † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Ulna fracture † 1       
# participants affected / at risk   0/2798 (0.00%)   2/2780 (0.07%)   0/3275 (0.00%) 
Fall † 1       
# participants affected / at risk   4/2798 (0.14%)   6/2780 (0.22%)   12/3275 (0.37%) 
Jaw fracture † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Muscle rupture † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Post procedural diarrhoea † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Procedural pain † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Road traffic accident † 1       
# participants affected / at risk   1/2798 (0.04%)   2/2780 (0.07%)   1/3275 (0.03%) 
Head injury † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   2/3275 (0.06%) 
Lower limb fracture † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   1/3275 (0.03%) 
Meniscus lesion † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Pubis fracture † 1       
# participants affected / at risk   2/2798 (0.07%)   1/2780 (0.04%)   2/3275 (0.06%) 
Spinal column injury † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Therapeutic agent toxicity † 1       
# participants affected / at risk   2/2798 (0.07%)   1/2780 (0.04%)   0/3275 (0.00%) 
Femur fracture † 1       
# participants affected / at risk   5/2798 (0.18%)   6/2780 (0.22%)   11/3275 (0.34%) 
Patella fracture † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   0/3275 (0.00%) 
Post procedural fistula † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Rib fracture † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   2/3275 (0.06%) 
Incisional hernia † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   3/3275 (0.09%) 
Traumatic haematoma † 1       
# participants affected / at risk   0/2798 (0.00%)   2/2780 (0.07%)   0/3275 (0.00%) 
Wound secretion † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Animal bite † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Ankle fracture † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   3/3275 (0.09%) 
Cervical vertebral fracture † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Femoral neck fracture † 1       
# participants affected / at risk   2/2798 (0.07%)   0/2780 (0.00%)   8/3275 (0.24%) 
Humerus fracture † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   0/3275 (0.00%) 
In-stent arterial restenosis † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
In-stent coronary artery restenosis † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Radius fracture † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Spinal compression fracture † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   2/3275 (0.06%) 
Contusion † 1       
# participants affected / at risk   2/2798 (0.07%)   1/2780 (0.04%)   0/3275 (0.00%) 
Facial bones fracture † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Hip fracture † 1       
# participants affected / at risk   5/2798 (0.18%)   4/2780 (0.14%)   12/3275 (0.37%) 
Injury † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Multiple injuries † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   2/3275 (0.06%) 
Overdose † 1       
# participants affected / at risk   3/2798 (0.11%)   5/2780 (0.18%)   3/3275 (0.09%) 
Subdural haematoma † 1       
# participants affected / at risk   4/2798 (0.14%)   2/2780 (0.07%)   5/3275 (0.15%) 
Thoracic vertebral fracture † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Abdominal wound dehiscence † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Accidental overdose † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Aortic injury † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Brain contusion † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Chest injury † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Confusion postoperative † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Craniocerebral injury † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Fibula fracture † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Fractured sacrum † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Incarcerated incisional hernia † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Laceration † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   3/3275 (0.09%) 
Ligament sprain † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Meniscus injury † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Pelvic fracture † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Periorbital haematoma † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Post procedural haematoma † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Post procedural haematuria † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Post procedural haemorrhage † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Procedural haemorrhage † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Scapula fracture † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Spinal fracture † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Stomal hernia † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Subarachnoid haemorrhage † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Tendon rupture † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Tibia fracture † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   3/3275 (0.09%) 
Toxicity to various agents † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   5/3275 (0.15%) 
Traumatic haemorrhage † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Wound evisceration † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Wrist fracture † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Investigations       
Blood magnesium decreased † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Cystoscopy † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Ejection fraction decreased † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Hepatic enzyme increased † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   0/3275 (0.00%) 
Angiogram † 1       
# participants affected / at risk   1/2798 (0.04%)   3/2780 (0.11%)   1/3275 (0.03%) 
Arteriogram coronary † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   1/3275 (0.03%) 
Heart rate irregular † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Red blood cell sedimentation rate increased † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Liver function test abnormal † 1       
# participants affected / at risk   1/2798 (0.04%)   2/2780 (0.07%)   0/3275 (0.00%) 
Prostatic specific antigen increased † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Weight decreased † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Arthroscopy † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Blood creatinine increased † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Ecg signs of myocardial ischaemia † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Haemoglobin decreased † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Heart rate abnormal † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Liver function test increased † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Platelet count decreased † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Metabolism and nutrition disorders       
Hypoglycaemia † 1       
# participants affected / at risk   8/2798 (0.29%)   3/2780 (0.11%)   12/3275 (0.37%) 
Diabetes mellitus inadequate control † 1       
# participants affected / at risk   0/2798 (0.00%)   2/2780 (0.07%)   3/3275 (0.09%) 
Gout † 1       
# participants affected / at risk   2/2798 (0.07%)   2/2780 (0.07%)   1/3275 (0.03%) 
Hyperkalaemia † 1       
# participants affected / at risk   0/2798 (0.00%)   2/2780 (0.07%)   5/3275 (0.15%) 
Malnutrition † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Decreased appetite † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   2/3275 (0.06%) 
Starvation † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Type 2 diabetes mellitus † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   2/3275 (0.06%) 
Cachexia † 1       
# participants affected / at risk   0/2798 (0.00%)   2/2780 (0.07%)   0/3275 (0.00%) 
Dehydration † 1       
# participants affected / at risk   7/2798 (0.25%)   5/2780 (0.18%)   11/3275 (0.34%) 
Hypokalaemia † 1       
# participants affected / at risk   0/2798 (0.00%)   3/2780 (0.11%)   2/3275 (0.06%) 
Hyponatraemia † 1       
# participants affected / at risk   4/2798 (0.14%)   3/2780 (0.11%)   6/3275 (0.18%) 
Obesity † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Electrolyte imbalance † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   2/3275 (0.06%) 
Hyperglycaemia † 1       
# participants affected / at risk   3/2798 (0.11%)   1/2780 (0.04%)   2/3275 (0.06%) 
Hypovolaemia † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Diabetes mellitus † 1       
# participants affected / at risk   5/2798 (0.18%)   4/2780 (0.14%)   6/3275 (0.18%) 
Diabetes with hyperosmolarity † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Hypernatraemia † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Hypomagnesaemia † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Hypophosphataemia † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Lactic acidosis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Metabolic acidosis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Musculoskeletal and connective tissue disorders       
Lumbar spinal stenosis † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   4/3275 (0.12%) 
Musculoskeletal stiffness † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Osteochondrosis † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Spinal column stenosis † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Myopathy † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Rotator cuff syndrome † 1       
# participants affected / at risk   0/2798 (0.00%)   2/2780 (0.07%)   1/3275 (0.03%) 
Spinal osteoarthritis † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   4/3275 (0.12%) 
Joint swelling † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Musculoskeletal chest pain † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   3/3275 (0.09%) 
Osteoarthritis † 1       
# participants affected / at risk   11/2798 (0.39%)   3/2780 (0.11%)   17/3275 (0.52%) 
Polyarthritis † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Intervertebral disc protrusion † 1       
# participants affected / at risk   0/2798 (0.00%)   4/2780 (0.14%)   4/3275 (0.12%) 
Muscle spasms † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Pain in extremity † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   0/3275 (0.00%) 
Systemic lupus erythematosus † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Back pain † 1       
# participants affected / at risk   5/2798 (0.18%)   3/2780 (0.11%)   9/3275 (0.27%) 
Gouty arthritis † 1       
# participants affected / at risk   1/2798 (0.04%)   2/2780 (0.07%)   2/3275 (0.06%) 
Haemarthrosis † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Muscle haemorrhage † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Osteopenia † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Arthralgia † 1       
# participants affected / at risk   1/2798 (0.04%)   2/2780 (0.07%)   2/3275 (0.06%) 
Musculoskeletal pain † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Arthritis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Bursitis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Inguinal mass † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Intervertebral disc degeneration † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Muscular weakness † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Myalgia † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Plantar fasciitis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Polymyalgia rheumatica † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Rhabdomyolysis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Rheumatoid arthritis † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Spinal pain † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Tendon pain † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast cancer † 1       
# participants affected / at risk   9/2798 (0.32%)   1/2780 (0.04%)   10/3275 (0.31%) 
Cholesteatoma † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Colon cancer metastatic † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   0/3275 (0.00%) 
Gastric cancer † 1       
# participants affected / at risk   1/2798 (0.04%)   2/2780 (0.07%)   2/3275 (0.06%) 
Laryngeal cancer † 1       
# participants affected / at risk   0/2798 (0.00%)   2/2780 (0.07%)   0/3275 (0.00%) 
Lip and/or oral cavity cancer † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Lung neoplasm malignant † 1       
# participants affected / at risk   3/2798 (0.11%)   5/2780 (0.18%)   15/3275 (0.46%) 
Neoplasm prostate † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Non-Hodgkin's lymphoma stage III † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Pancreatic carcinoma † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   6/3275 (0.18%) 
Prostatic adenoma † 1       
# participants affected / at risk   2/2798 (0.07%)   0/2780 (0.00%)   3/3275 (0.09%) 
Uterine leiomyoma † 1       
# participants affected / at risk   0/2798 (0.00%)   2/2780 (0.07%)   2/3275 (0.06%) 
Bladder cancer † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   4/3275 (0.12%) 
Brain neoplasm benign † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Omentum neoplasm † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Renal cell carcinoma † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   2/3275 (0.06%) 
Breast cancer metastatic † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Bronchial carcinoma † 1       
# participants affected / at risk   0/2798 (0.00%)   2/2780 (0.07%)   0/3275 (0.00%) 
Leukaemia † 1       
# participants affected / at risk   2/2798 (0.07%)   0/2780 (0.00%)   1/3275 (0.03%) 
Metastases to abdominal cavity † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Biliary neoplasm † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Hepatic neoplasm malignant † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   0/3275 (0.00%) 
Malignant melanoma † 1       
# participants affected / at risk   1/2798 (0.04%)   2/2780 (0.07%)   2/3275 (0.06%) 
Lipoma † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Lung adenocarcinoma metastatic † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Lung cancer metastatic † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Lymph node cancer metastatic † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Metastases to central nervous system † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Neoplasm malignant † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   1/3275 (0.03%) 
Rectal cancer metastatic † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Sebaceous carcinoma † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Squamous cell carcinoma † 1       
# participants affected / at risk   2/2798 (0.07%)   4/2780 (0.14%)   7/3275 (0.21%) 
Cervix carcinoma stage 0 † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Gastrointestinal carcinoma † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   1/3275 (0.03%) 
Leiomyoma † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Malignant melanoma stage I † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Pelvic neoplasm † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Renal cancer stage III † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Squamous cell carcinoma of skin † 1       
# participants affected / at risk   2/2798 (0.07%)   0/2780 (0.00%)   4/3275 (0.12%) 
Basal cell carcinoma † 1       
# participants affected / at risk   5/2798 (0.18%)   5/2780 (0.18%)   12/3275 (0.37%) 
Basosquamous carcinoma † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Colon cancer † 1       
# participants affected / at risk   2/2798 (0.07%)   1/2780 (0.04%)   5/3275 (0.15%) 
Liposarcoma † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Prostate cancer recurrent † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Renal neoplasm † 1       
# participants affected / at risk   1/2798 (0.04%)   1/2780 (0.04%)   0/3275 (0.00%) 
Colon neoplasm † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Endometrial cancer † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   0/3275 (0.00%) 
Gallbladder cancer † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Lymphoma † 1       
# participants affected / at risk   1/2798 (0.04%)   0/2780 (0.00%)   2/3275 (0.06%) 
Metastases to liver † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Prostate cancer † 1       
# participants affected / at risk   7/2798 (0.25%)   10/2780 (0.36%)   12/3275 (0.37%) 
Rectal cancer † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   0/3275 (0.00%) 
Renal cancer † 1       
# participants affected / at risk   0/2798 (0.00%)   1/2780 (0.04%)   1/3275 (0.03%) 
Squamous cell carcinoma of the cervix † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Acute myeloid leukaemia † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Adenocarcinoma gastric † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Adenocarcinoma of colon † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Adrenal adenoma † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
B-cell lymphoma † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
B-cell small lymphocytic lymphoma stage iv † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Bladder cancer stage 0, with cancer in situ † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Bladder neoplasm † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Bowen's disease † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Brain cancer metastatic † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Brain neoplasm † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   4/3275 (0.12%) 
Carcinoid tumour of the caecum † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Cholangiocarcinoma † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Chronic lymphocytic leukaemia † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Colorectal cancer † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Diffuse large b-cell lymphoma † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Gastrointestinal stromal tumour † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Hepatocellular carcinoma † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Intraductal papillary mucinous neoplasm † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Intraocular melanoma † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Invasive ductal breast carcinoma † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Leiomyosarcoma metastatic † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Light chain disease † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Lung adenocarcinoma † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Lung neoplasm † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Meningioma † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Metastases to bone † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Metastases to pleura † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Metastatic neoplasm † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   2/3275 (0.06%) 
Metastatic renal cell carcinoma † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Myeloproliferative neoplasm † 1       
# participants affected / at risk   0/2798 (0.00%)   0/2780 (0.00%)   1/3275 (0.03%) 
Neoplasm † 1       
# participants affected / at risk   0/2798 (0.00%)