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RED-HF™ Trial - Reduction of Events With Darbepoetin Alfa in Heart Failure Trial

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00358215
First received: July 27, 2006
Last updated: July 14, 2014
Last verified: July 2014
Results First Received: October 23, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Heart Failure
Anemia
Cardiovascular Disease
Ventricular Dysfunction
Congestive Heart Failure
Interventions: Drug: Darbepoetin alfa
Drug: 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 enrolled 13 June 2006; Last patient enrolled 4 May 2012

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

Reporting Groups
  Description
Placebo Participants received dose and administration schedule (every 2 weeks or once a month) changes that simulated the changes for participants receiving darbepoetin alfa.
Darbepoetin Alfa Starting dose of 0.75 µg/kg subcutaneously every 2 weeks until hemoglobin concentrations reach 13.0 g/dL on 2 consecutive visits, then monthly dosing, titrated to achieve hemoglobin target of 13.0 g/dL, not to exceed 14.5 g/dL.

Participant Flow:   Overall Study
    Placebo     Darbepoetin Alfa  
STARTED     1142     1136  
Received Investigational Product     1140     1133  
COMPLETED     463 [1]   484 [1]
NOT COMPLETED     679     652  
Ineligibility determined                 4                 3  
Adverse Event                 83                 65  
Withdrawal by Subject                 111                 102  
Participant request                 65                 64  
Physician Decision                 47                 39  
Lost to Follow-up                 16                 22  
Death                 265                 281  
Protocol Violation                 64                 59  
Pregnancy                 1                 0  
Other                 21                 14  
Did not receive investigational product                 2                 3  
[1] Participants who completed investigational product



  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
Placebo Participants received dose and administration schedule (every 2 weeks or once a month) changes that simulated the changes for participants receiving darbepoetin alfa.
Darbepoetin Alfa Starting dose of 0.75 µg/kg subcutaneously every 2 weeks until hemoglobin concentrations reach 13.0 g/dL on 2 consecutive visits, then monthly dosing, titrated to achieve hemoglobin target of 13.0 g/dL, not to exceed 14.5 g/dL.
Total Total of all reporting groups

Baseline Measures
    Placebo     Darbepoetin Alfa     Total  
Number of Participants  
[units: participants]
  1142     1136     2278  
Age  
[units: years]
Mean ± Standard Deviation
  69.6  ± 11.3     70.0  ± 11.6     69.8  ± 11.4  
Gender  
[units: participants]
     
Female     486     458     944  
Male     656     678     1334  
Race/Ethnicity, Customized  
[units: participants]
     
White or Caucasian     768     781     1549  
Black or African American     113     89     202  
Hispanic or Latino     84     98     182  
Asian     162     162     324  
Japanese     0     1     1  
American Indian or Alaska Native     2     2     4  
Native Hawaiian or Other Pacific Islander     1     0     1  
Other     12     3     15  
Region  
[units: participants]
     
North America     323     321     644  
Latin America and Asia     286     285     571  
Western Europe, Israel, South Africa, Australia     306     303     609  
Eastern Europe and Russia     227     227     454  
Device Usage [1]
[units: participants]
     
CRT with or without ICD     143     143     286  
ICD without CRT     124     122     246  
None     875     871     1746  
Kansas City Cardiomyopathy Questionnaire: Overall Summary Score [2]
[units: units on a scale]
Mean ± Standard Deviation
  56.5  ± 22.5     55.8  ± 22.6     56.2  ± 22.5  
Study Specific Characteristic [Kansas City Cardiomyopathy Questionnaire: Symptom Frequency Scale [2]
[units: units on a scale]
Mean ± Standard Deviation
  63.3  ± 25.2     63.1  ± 25.6     63.2  ± 25.4  
[1] Usage of implantable cardioverter defibrillator / cardiac resynchronization therapy (ICD/CRT)
[2] The KCCQ is a patient-reported measure for patients with heart failure. It consists of 23 items, is comprised of 7 clinically relevant scales (Symptom Frequency, Burden and Stability, Physical and Social Limitation, Quality of Life, and Self-Efficacy), and yields 3 summary scores (Clinical Summary, Total Symptom, and Overall Summary Scores). Scores range between 0 and 100, with higher scores indicating better health status (eg, better functioning, quality of life, fewer symptoms). Number of participants with available data = 1106 and 1104 for each treatment group respectively, total = 2210.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Time to All Cause Death or First Hospitalization for Worsening Heart Failure   [ Time Frame: From randomization to the end of study; maximum time on study was 73 months ]

2.  Secondary:   Time to Death From Any Cause   [ Time Frame: From randomization to the end of study; maximum time on study was 73 months ]

3.  Secondary:   Time to Cardiovascular Death or First Hospital Admission for Worsening Heart Failure   [ Time Frame: From randomization to the end of study; maximum time on study was 73 months ]

4.  Secondary:   Change From Baseline to Month 6 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score   [ Time Frame: Baseline and Month 6 ]

5.  Secondary:   Change From Baseline to Month 6 in KCCQ Symptom Frequency Score   [ Time Frame: Baseline and Month 6 ]


  Serious Adverse Events
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Time Frame Informed consent to 30 days post treatment. Max time 72 months
Additional Description The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Reporting Groups
  Description
Placebo Participants received dose and administration schedule (every 2 weeks or once a month) changes that simulated the changes for participants receiving darbepoetin alfa.
Darbepoetin Alfa Starting dose of 0.75 µg/kg subcutaneously every 2 weeks until hemoglobin concentrations reach 13.0 g/dL on 2 consecutive visits, then monthly dosing, titrated to achieve hemoglobin target of 13.0 g/dL, not to exceed 14.5 g/dL.

Serious Adverse Events
    Placebo     Darbepoetin Alfa  
Total, serious adverse events      
# participants affected / at risk     741/1140 (65.00%)     781/1133 (68.93%)  
Blood and lymphatic system disorders      
Anaemia † 1    
# participants affected / at risk     49/1140 (4.30%)     23/1133 (2.03%)  
Anaemia of chronic disease † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Coagulopathy † 1    
# participants affected / at risk     1/1140 (0.09%)     2/1133 (0.18%)  
Haemolytic anaemia † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Haemorrhagic anaemia † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Heparin-induced thrombocytopenia † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Iron deficiency anaemia † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Leukocytosis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Lymphadenopathy † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Pancytopenia † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Sideroblastic anaemia † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Splenic infarction † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Thrombocytopenia † 1    
# participants affected / at risk     1/1140 (0.09%)     2/1133 (0.18%)  
Cardiac disorders      
Acute coronary syndrome † 1    
# participants affected / at risk     13/1140 (1.14%)     7/1133 (0.62%)  
Acute left ventricular failure † 1    
# participants affected / at risk     5/1140 (0.44%)     5/1133 (0.44%)  
Acute myocardial infarction † 1    
# participants affected / at risk     21/1140 (1.84%)     21/1133 (1.85%)  
Adams-Stokes syndrome † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Angina pectoris † 1    
# participants affected / at risk     27/1140 (2.37%)     26/1133 (2.29%)  
Angina unstable † 1    
# participants affected / at risk     26/1140 (2.28%)     24/1133 (2.12%)  
Aortic valve incompetence † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Aortic valve stenosis † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Arrhythmia † 1    
# participants affected / at risk     10/1140 (0.88%)     5/1133 (0.44%)  
Arrhythmia supraventricular † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Arteriosclerosis coronary artery † 1    
# participants affected / at risk     2/1140 (0.18%)     1/1133 (0.09%)  
Atrial fibrillation † 1    
# participants affected / at risk     30/1140 (2.63%)     32/1133 (2.82%)  
Atrial flutter † 1    
# participants affected / at risk     7/1140 (0.61%)     3/1133 (0.26%)  
Atrial tachycardia † 1    
# participants affected / at risk     2/1140 (0.18%)     2/1133 (0.18%)  
Atrioventricular block † 1    
# participants affected / at risk     3/1140 (0.26%)     2/1133 (0.18%)  
Atrioventricular block complete † 1    
# participants affected / at risk     2/1140 (0.18%)     2/1133 (0.18%)  
Bradyarrhythmia † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Bradycardia † 1    
# participants affected / at risk     4/1140 (0.35%)     7/1133 (0.62%)  
Bundle branch block left † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Cardiac arrest † 1    
# participants affected / at risk     22/1140 (1.93%)     31/1133 (2.74%)  
Cardiac asthma † 1    
# participants affected / at risk     3/1140 (0.26%)     2/1133 (0.18%)  
Cardiac discomfort † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Cardiac disorder † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Cardiac failure † 1    
# participants affected / at risk     273/1140 (23.95%)     264/1133 (23.30%)  
Cardiac failure acute † 1    
# participants affected / at risk     16/1140 (1.40%)     21/1133 (1.85%)  
Cardiac failure chronic † 1    
# participants affected / at risk     8/1140 (0.70%)     9/1133 (0.79%)  
Cardiac failure congestive † 1    
# participants affected / at risk     145/1140 (12.72%)     126/1133 (11.12%)  
Cardiac valve disease † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Cardio-respiratory arrest † 1    
# participants affected / at risk     10/1140 (0.88%)     14/1133 (1.24%)  
Cardiogenic shock † 1    
# participants affected / at risk     11/1140 (0.96%)     17/1133 (1.50%)  
Cardiomyopathy † 1    
# participants affected / at risk     4/1140 (0.35%)     2/1133 (0.18%)  
Cardiopulmonary failure † 1    
# participants affected / at risk     0/1140 (0.00%)     5/1133 (0.44%)  
Cardiorenal syndrome † 1    
# participants affected / at risk     1/1140 (0.09%)     2/1133 (0.18%)  
Cardiovascular insufficiency † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Congestive cardiomyopathy † 1    
# participants affected / at risk     2/1140 (0.18%)     1/1133 (0.09%)  
Coronary artery disease † 1    
# participants affected / at risk     10/1140 (0.88%)     4/1133 (0.35%)  
Coronary artery occlusion † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Coronary artery stenosis † 1    
# participants affected / at risk     4/1140 (0.35%)     0/1133 (0.00%)  
Coronary artery thrombosis † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Hypertensive heart disease † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Intracardiac thrombus † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Ischaemic cardiomyopathy † 1    
# participants affected / at risk     5/1140 (0.44%)     6/1133 (0.53%)  
Left ventricular dysfunction † 1    
# participants affected / at risk     1/1140 (0.09%)     3/1133 (0.26%)  
Left ventricular failure † 1    
# participants affected / at risk     3/1140 (0.26%)     3/1133 (0.26%)  
Mitral valve disease † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Mitral valve incompetence † 1    
# participants affected / at risk     4/1140 (0.35%)     2/1133 (0.18%)  
Mitral valve stenosis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Myocardial fibrosis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Myocardial infarction † 1    
# participants affected / at risk     35/1140 (3.07%)     36/1133 (3.18%)  
Myocardial ischaemia † 1    
# participants affected / at risk     5/1140 (0.44%)     1/1133 (0.09%)  
Palpitations † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Pericardial effusion † 1    
# participants affected / at risk     1/1140 (0.09%)     2/1133 (0.18%)  
Pericarditis † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Pulseless electrical activity † 1    
# participants affected / at risk     1/1140 (0.09%)     2/1133 (0.18%)  
Right ventricular failure † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Sick sinus syndrome † 1    
# participants affected / at risk     3/1140 (0.26%)     1/1133 (0.09%)  
Sinoatrial block † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Sinus arrhythmia † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Sinus bradycardia † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Supraventricular tachycardia † 1    
# participants affected / at risk     2/1140 (0.18%)     2/1133 (0.18%)  
Tachyarrhythmia † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Tachycardia † 1    
# participants affected / at risk     2/1140 (0.18%)     1/1133 (0.09%)  
Tachycardia paroxysmal † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Tricuspid valve incompetence † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Ventricular arrhythmia † 1    
# participants affected / at risk     3/1140 (0.26%)     6/1133 (0.53%)  
Ventricular extrasystoles † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Ventricular fibrillation † 1    
# participants affected / at risk     10/1140 (0.88%)     10/1133 (0.88%)  
Ventricular tachyarrhythmia † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Ventricular tachycardia † 1    
# participants affected / at risk     24/1140 (2.11%)     22/1133 (1.94%)  
Congenital, familial and genetic disorders      
Arteriovenous malformation † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Gastrointestinal arteriovenous malformation † 1    
# participants affected / at risk     2/1140 (0.18%)     1/1133 (0.09%)  
Ichthyosis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Ear and labyrinth disorders      
Vertigo † 1    
# participants affected / at risk     2/1140 (0.18%)     1/1133 (0.09%)  
Endocrine disorders      
Adrenal insufficiency † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Hyperparathyroidism † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Hyperthyroidism † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Hypothyroidism † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Inappropriate antidiuretic hormone secretion † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Eye disorders      
Cataract † 1    
# participants affected / at risk     1/1140 (0.09%)     3/1133 (0.26%)  
Cataract diabetic † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Diabetic retinopathy † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Macular fibrosis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Optic ischaemic neuropathy † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Retinal artery occlusion † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Retinal detachment † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Retinal vein occlusion † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Retinopathy † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Scleral haemorrhage † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Vision blurred † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Visual acuity reduced † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Vitreous haemorrhage † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Gastrointestinal disorders      
Abdominal adhesions † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Abdominal discomfort † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Abdominal distension † 1    
# participants affected / at risk     2/1140 (0.18%)     2/1133 (0.18%)  
Abdominal hernia † 1    
# participants affected / at risk     2/1140 (0.18%)     1/1133 (0.09%)  
Abdominal pain † 1    
# participants affected / at risk     6/1140 (0.53%)     13/1133 (1.15%)  
Abdominal pain lower † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Abdominal pain upper † 1    
# participants affected / at risk     3/1140 (0.26%)     5/1133 (0.44%)  
Abdominal wall haematoma † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Abdominal wall haemorrhage † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Anal polyp † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Ascites † 1    
# participants affected / at risk     3/1140 (0.26%)     1/1133 (0.09%)  
Coeliac disease † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Colitis † 1    
# participants affected / at risk     2/1140 (0.18%)     3/1133 (0.26%)  
Colitis ischaemic † 1    
# participants affected / at risk     2/1140 (0.18%)     1/1133 (0.09%)  
Colonic polyp † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Colonic stenosis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Constipation † 1    
# participants affected / at risk     8/1140 (0.70%)     9/1133 (0.79%)  
Crohn's disease † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Diabetic gastroparesis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Diaphragmatic hernia † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Diarrhoea † 1    
# participants affected / at risk     12/1140 (1.05%)     12/1133 (1.06%)  
Diverticular perforation † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Diverticulum † 1    
# participants affected / at risk     2/1140 (0.18%)     3/1133 (0.26%)  
Diverticulum intestinal haemorrhagic † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Duodenal ulcer † 1    
# participants affected / at risk     2/1140 (0.18%)     3/1133 (0.26%)  
Duodenal ulcer haemorrhage † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Duodenitis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Dyspepsia † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Dysphagia † 1    
# participants affected / at risk     0/1140 (0.00%)     4/1133 (0.35%)  
Enterocolitis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Epigastric discomfort † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Erosive oesophagitis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Faecaloma † 1    
# participants affected / at risk     2/1140 (0.18%)     1/1133 (0.09%)  
Functional gastrointestinal disorder † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Gastric haemorrhage † 1    
# participants affected / at risk     2/1140 (0.18%)     3/1133 (0.26%)  
Gastric ulcer † 1    
# participants affected / at risk     4/1140 (0.35%)     2/1133 (0.18%)  
Gastric ulcer haemorrhage † 1    
# participants affected / at risk     1/1140 (0.09%)     2/1133 (0.18%)  
Gastric ulcer perforation † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Gastritis † 1    
# participants affected / at risk     4/1140 (0.35%)     4/1133 (0.35%)  
Gastritis atrophic † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Gastritis erosive † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Gastritis haemorrhagic † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Gastrointestinal angiodysplasia † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Gastrointestinal haemorrhage † 1    
# participants affected / at risk     23/1140 (2.02%)     18/1133 (1.59%)  
Gastrointestinal inflammation † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Gastrointestinal obstruction † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Gastrooesophageal reflux disease † 1    
# participants affected / at risk     2/1140 (0.18%)     2/1133 (0.18%)  
Gingival bleeding † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Haematemesis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Haemorrhoidal haemorrhage † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Haemorrhoids † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Hiatus hernia † 1    
# participants affected / at risk     1/1140 (0.09%)     2/1133 (0.18%)  
Ileus † 1    
# participants affected / at risk     0/1140 (0.00%)     3/1133 (0.26%)  
Impaired gastric emptying † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Inflammatory bowel disease † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Inguinal hernia † 1    
# participants affected / at risk     5/1140 (0.44%)     6/1133 (0.53%)  
Inguinal hernia, obstructive † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Intestinal haemorrhage † 1    
# participants affected / at risk     2/1140 (0.18%)     1/1133 (0.09%)  
Intestinal infarction † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Intestinal ischaemia † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Intestinal mass † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Intestinal obstruction † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Intestinal polyp † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Irritable bowel syndrome † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Large intestinal ulcer † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Lower gastrointestinal haemorrhage † 1    
# participants affected / at risk     1/1140 (0.09%)     3/1133 (0.26%)  
Mallory-Weiss syndrome † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Melaena † 1    
# participants affected / at risk     3/1140 (0.26%)     1/1133 (0.09%)  
Nausea † 1    
# participants affected / at risk     5/1140 (0.44%)     6/1133 (0.53%)  
Oesophageal achalasia † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Oesophageal food impaction † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Oesophageal motility disorder † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Oesophagitis † 1    
# participants affected / at risk     1/1140 (0.09%)     3/1133 (0.26%)  
Pancreatitis † 1    
# participants affected / at risk     2/1140 (0.18%)     3/1133 (0.26%)  
Pancreatitis acute † 1    
# participants affected / at risk     3/1140 (0.26%)     1/1133 (0.09%)  
Pancreatitis chronic † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Peptic ulcer † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Peptic ulcer haemorrhage † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Poor dental condition † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Proctalgia † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Rectal haemorrhage † 1    
# participants affected / at risk     4/1140 (0.35%)     5/1133 (0.44%)  
Rectal polyp † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Small intestinal obstruction † 1    
# participants affected / at risk     2/1140 (0.18%)     2/1133 (0.18%)  
Subileus † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Thrombosis mesenteric vessel † 1    
# participants affected / at risk     0/1140 (0.00%)     3/1133 (0.26%)  
Toothache † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Umbilical hernia † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Umbilical hernia, obstructive † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Upper gastrointestinal haemorrhage † 1    
# participants affected / at risk     2/1140 (0.18%)     5/1133 (0.44%)  
Varices oesophageal † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Volvulus † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Vomiting † 1    
# participants affected / at risk     9/1140 (0.79%)     9/1133 (0.79%)  
General disorders      
Adverse drug reaction † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Asthenia † 1    
# participants affected / at risk     10/1140 (0.88%)     8/1133 (0.71%)  
Cardiac death † 1    
# participants affected / at risk     29/1140 (2.54%)     34/1133 (3.00%)  
Catheter site haemorrhage † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Chest discomfort † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Chest pain † 1    
# participants affected / at risk     3/1140 (0.26%)     2/1133 (0.18%)  
Death † 1    
# participants affected / at risk     24/1140 (2.11%)     18/1133 (1.59%)  
Device breakage † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Device dislocation † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Device lead damage † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Device malfunction † 1    
# participants affected / at risk     8/1140 (0.70%)     10/1133 (0.88%)  
Device misuse † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Device stimulation issue † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Drowning † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Fatigue † 1    
# participants affected / at risk     2/1140 (0.18%)     2/1133 (0.18%)  
General physical health deterioration † 1    
# participants affected / at risk     3/1140 (0.26%)     5/1133 (0.44%)  
Generalised oedema † 1    
# participants affected / at risk     1/1140 (0.09%)     3/1133 (0.26%)  
Hernia † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Hyperpyrexia † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Hypothermia † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Impaired healing † 1    
# participants affected / at risk     1/1140 (0.09%)     2/1133 (0.18%)  
Implant site haematoma † 1    
# participants affected / at risk     1/1140 (0.09%)     2/1133 (0.18%)  
Implant site pain † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Implant site ulcer † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Inflammation † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Malaise † 1    
# participants affected / at risk     2/1140 (0.18%)     1/1133 (0.09%)  
Medical device complication † 1    
# participants affected / at risk     0/1140 (0.00%)     4/1133 (0.35%)  
Medical device pain † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Medical device site reaction † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Multi-organ disorder † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Multi-organ failure † 1    
# participants affected / at risk     13/1140 (1.14%)     5/1133 (0.44%)  
Necrobiosis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Non-cardiac chest pain † 1    
# participants affected / at risk     27/1140 (2.37%)     22/1133 (1.94%)  
Oedema † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Oedema peripheral † 1    
# participants affected / at risk     2/1140 (0.18%)     4/1133 (0.35%)  
Pain † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Polyp † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Pyrexia † 1    
# participants affected / at risk     8/1140 (0.70%)     8/1133 (0.71%)  
Sudden cardiac death † 1    
# participants affected / at risk     8/1140 (0.70%)     21/1133 (1.85%)  
Sudden death † 1    
# participants affected / at risk     19/1140 (1.67%)     11/1133 (0.97%)  
Systemic inflammatory response syndrome † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Thrombosis in device † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Hepatobiliary disorders      
Bile duct stone † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Biliary colic † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Cardiac cirrhosis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Cholangitis † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Cholecystitis † 1    
# participants affected / at risk     3/1140 (0.26%)     5/1133 (0.44%)  
Cholecystitis acute † 1    
# participants affected / at risk     3/1140 (0.26%)     4/1133 (0.35%)  
Cholecystitis chronic † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Cholelithiasis † 1    
# participants affected / at risk     2/1140 (0.18%)     9/1133 (0.79%)  
Gallbladder non-functioning † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Hepatic cirrhosis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Hepatic congestion † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Hepatic failure † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Hepatic lesion † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Hepatitis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Hepatomegaly † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Hepatorenal failure † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Liver disorder † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Immune system disorders      
Heart transplant rejection † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Hypogammaglobulinaemia † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Sarcoidosis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Infections and infestations      
Abdominal abscess † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Abdominal infection † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Abscess limb † 1    
# participants affected / at risk     0/1140 (0.00%)     3/1133 (0.26%)  
Abscess neck † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Appendicitis † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Arthritis bacterial † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Arthritis infective † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Bacteraemia † 1    
# participants affected / at risk     5/1140 (0.44%)     1/1133 (0.09%)  
Bacterial infection † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Bacterial sepsis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Bone tuberculosis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Bronchitis † 1    
# participants affected / at risk     22/1140 (1.93%)     12/1133 (1.06%)  
Bronchitis bacterial † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Bronchopneumonia † 1    
# participants affected / at risk     4/1140 (0.35%)     5/1133 (0.44%)  
Campylobacter infection † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Catheter site infection † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Cellulitis † 1    
# participants affected / at risk     16/1140 (1.40%)     18/1133 (1.59%)  
Clostridial infection † 1    
# participants affected / at risk     1/1140 (0.09%)     3/1133 (0.26%)  
Clostridium difficile colitis † 1    
# participants affected / at risk     2/1140 (0.18%)     3/1133 (0.26%)  
Clostridium difficile sepsis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Cystitis † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Device related infection † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Diabetic foot infection † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Diabetic gangrene † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Diarrhoea infectious † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Diverticulitis † 1    
# participants affected / at risk     1/1140 (0.09%)     4/1133 (0.35%)  
Endocarditis † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Enterococcal sepsis † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Erysipelas † 1    
# participants affected / at risk     3/1140 (0.26%)     5/1133 (0.44%)  
Escherichia bacteraemia † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Escherichia urinary tract infection † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
External ear cellulitis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Fungaemia † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Gangrene † 1    
# participants affected / at risk     4/1140 (0.35%)     1/1133 (0.09%)  
Gastroenteritis † 1    
# participants affected / at risk     7/1140 (0.61%)     15/1133 (1.32%)  
Gastroenteritis clostridial † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Gastroenteritis viral † 1    
# participants affected / at risk     3/1140 (0.26%)     2/1133 (0.18%)  
H1N1 influenza † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Helicobacter gastritis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Herpes zoster † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Implant site infection † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Incision site infection † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Infected skin ulcer † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Infection † 1    
# participants affected / at risk     1/1140 (0.09%)     3/1133 (0.26%)  
Infective exacerbation of chronic obstructive airways disease † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Influenza † 1    
# participants affected / at risk     0/1140 (0.00%)     3/1133 (0.26%)  
Lobar pneumonia † 1    
# participants affected / at risk     8/1140 (0.70%)     8/1133 (0.71%)  
Localised infection † 1    
# participants affected / at risk     7/1140 (0.61%)     5/1133 (0.44%)  
Lower respiratory tract infection † 1    
# participants affected / at risk     6/1140 (0.53%)     7/1133 (0.62%)  
Lung infection † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Lung infection pseudomonal † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Malaria † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Neutropenic sepsis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Nosocomial infection † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Oropharyngitis fungal † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Osteomyelitis † 1    
# participants affected / at risk     5/1140 (0.44%)     5/1133 (0.44%)  
Osteomyelitis chronic † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Otitis externa † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Pelvic abscess † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Peritonitis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Pneumococcal bacteraemia † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Pneumonia † 1    
# participants affected / at risk     71/1140 (6.23%)     86/1133 (7.59%)  
Pneumonia bacterial † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Pneumonia escherichia † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Pneumonia influenzal † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Pneumonia klebsiella † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Pneumonia staphylococcal † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Post procedural infection † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Postoperative wound infection † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Pseudomonal sepsis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Pulmonary sepsis † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Pyelonephritis † 1    
# participants affected / at risk     1/1140 (0.09%)     3/1133 (0.26%)  
Pyelonephritis chronic † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Rectal abscess † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Respiratory tract infection † 1    
# participants affected / at risk     4/1140 (0.35%)     10/1133 (0.88%)  
Respiratory tract infection viral † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Sepsis † 1    
# participants affected / at risk     22/1140 (1.93%)     19/1133 (1.68%)  
Septic shock † 1    
# participants affected / at risk     7/1140 (0.61%)     21/1133 (1.85%)  
Sinusitis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Soft tissue infection † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Staphylococcal infection † 1    
# participants affected / at risk     1/1140 (0.09%)     3/1133 (0.26%)  
Staphylococcal osteomyelitis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Staphylococcal sepsis † 1    
# participants affected / at risk     3/1140 (0.26%)     0/1133 (0.00%)  
Streptococcal infection † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Subcutaneous abscess † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Superinfection † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Tracheobronchitis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Tuberculous pleurisy † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Upper respiratory tract infection † 1    
# participants affected / at risk     3/1140 (0.26%)     4/1133 (0.35%)  
Urinary tract infection † 1    
# participants affected / at risk     20/1140 (1.75%)     29/1133 (2.56%)  
Urosepsis † 1    
# participants affected / at risk     9/1140 (0.79%)     8/1133 (0.71%)  
Viral infection † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Wound infection † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Wound sepsis † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Injury, poisoning and procedural complications      
Accidental overdose † 1    
# participants affected / at risk     2/1140 (0.18%)     1/1133 (0.09%)  
Acetabulum fracture † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Alcohol poisoning † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Ankle fracture † 1    
# participants affected / at risk     2/1140 (0.18%)     1/1133 (0.09%)  
Burns third degree † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Cervical vertebral fracture † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Chest injury † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Concussion † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Confusion postoperative † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Contusion † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Craniocerebral injury † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Cystitis radiation † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Drug administered at inappropriate site † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Eschar † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Fall † 1    
# participants affected / at risk     8/1140 (0.70%)     16/1133 (1.41%)  
Femoral neck fracture † 1    
# participants affected / at risk     5/1140 (0.44%)     7/1133 (0.62%)  
Femur fracture † 1    
# participants affected / at risk     8/1140 (0.70%)     8/1133 (0.71%)  
Fibula fracture † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Foot fracture † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Gun shot wound † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Head injury † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Hip fracture † 1    
# participants affected / at risk     18/1140 (1.58%)     14/1133 (1.24%)  
Humerus fracture † 1    
# participants affected / at risk     3/1140 (0.26%)     3/1133 (0.26%)  
Incisional hernia † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Injury † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Intentional overdose † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Joint dislocation † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Laceration † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Ligament sprain † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Lower limb fracture † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Lumbar vertebral fracture † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Multiple fractures † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Multiple injuries † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Overdose † 1    
# participants affected / at risk     4/1140 (0.35%)     3/1133 (0.26%)  
Pelvic fracture † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Poisoning † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Post procedural complication † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Post procedural haematoma † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Post procedural haemorrhage † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Procedural haemorrhage † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Pubis fracture † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Radius fracture † 1    
# participants affected / at risk     1/1140 (0.09%)     2/1133 (0.18%)  
Rib fracture † 1    
# participants affected / at risk     1/1140 (0.09%)     3/1133 (0.26%)  
Road traffic accident † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Shunt occlusion † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Soft tissue injury † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Spinal compression fracture † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Spinal fracture † 1    
# participants affected / at risk     2/1140 (0.18%)     1/1133 (0.09%)  
Subdural haematoma † 1    
# participants affected / at risk     7/1140 (0.61%)     2/1133 (0.18%)  
Subdural haemorrhage † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Tendon rupture † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Tibia fracture † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Toxicity to various agents † 1    
# participants affected / at risk     7/1140 (0.61%)     5/1133 (0.44%)  
Tracheal obstruction † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Transfusion reaction † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Traumatic haematoma † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Ulna fracture † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Upper limb fracture † 1    
# participants affected / at risk     3/1140 (0.26%)     6/1133 (0.53%)  
Wound † 1    
# participants affected / at risk     1/1140 (0.09%)     2/1133 (0.18%)  
Wound necrosis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Wrist fracture † 1    
# participants affected / at risk     2/1140 (0.18%)     1/1133 (0.09%)  
Investigations      
Arteriogram coronary † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Blood glucose decreased † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Blood glucose increased † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Blood potassium increased † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Blood uric acid increased † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
C-reactive protein abnormal † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
C-reactive protein increased † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Cardiac output decreased † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Coagulation time prolonged † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Drug level increased † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Ejection fraction decreased † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Glycosylated haemoglobin increased † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Haemodynamic test abnormal † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Haemoglobin decreased † 1    
# participants affected / at risk     3/1140 (0.26%)     1/1133 (0.09%)  
International normalised ratio abnormal † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
International normalised ratio increased † 1    
# participants affected / at risk     4/1140 (0.35%)     5/1133 (0.44%)  
Liver function test abnormal † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Occult blood † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Occult blood positive † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Platelet count decreased † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Renal function test abnormal † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Transaminases increased † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Transferrin saturation decreased † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Waist circumference increased † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Weight decreased † 1    
# participants affected / at risk     1/1140 (0.09%)     2/1133 (0.18%)  
Weight increased † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Metabolism and nutrition disorders      
Cachexia † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Calciphylaxis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Decreased appetite † 1    
# participants affected / at risk     5/1140 (0.44%)     1/1133 (0.09%)  
Dehydration † 1    
# participants affected / at risk     22/1140 (1.93%)     19/1133 (1.68%)  
Diabetes mellitus † 1    
# participants affected / at risk     9/1140 (0.79%)     14/1133 (1.24%)  
Diabetes mellitus inadequate control † 1    
# participants affected / at risk     5/1140 (0.44%)     6/1133 (0.53%)  
Diabetic complication † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Electrolyte imbalance † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Failure to thrive † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Fluid overload † 1    
# participants affected / at risk     2/1140 (0.18%)     2/1133 (0.18%)  
Gout † 1    
# participants affected / at risk     10/1140 (0.88%)     5/1133 (0.44%)  
Hypercalcaemia † 1    
# participants affected / at risk     2/1140 (0.18%)     1/1133 (0.09%)  
Hyperglycaemia † 1    
# participants affected / at risk     13/1140 (1.14%)     7/1133 (0.62%)  
Hyperkalaemia † 1    
# participants affected / at risk     15/1140 (1.32%)     13/1133 (1.15%)  
Hyperlipidaemia † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Hypocalcaemia † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Hypoglycaemia † 1    
# participants affected / at risk     18/1140 (1.58%)     16/1133 (1.41%)  
Hypokalaemia † 1    
# participants affected / at risk     6/1140 (0.53%)     9/1133 (0.79%)  
Hyponatraemia † 1    
# participants affected / at risk     11/1140 (0.96%)     7/1133 (0.62%)  
Hypovolaemia † 1    
# participants affected / at risk     5/1140 (0.44%)     6/1133 (0.53%)  
Lactic acidosis † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Type 1 diabetes mellitus † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Type 2 diabetes mellitus † 1    
# participants affected / at risk     3/1140 (0.26%)     0/1133 (0.00%)  
Musculoskeletal and connective tissue disorders      
Arthralgia † 1    
# participants affected / at risk     3/1140 (0.26%)     4/1133 (0.35%)  
Arthritis † 1    
# participants affected / at risk     3/1140 (0.26%)     0/1133 (0.00%)  
Arthritis reactive † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Back pain † 1    
# participants affected / at risk     7/1140 (0.61%)     4/1133 (0.35%)  
Bone infarction † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Costochondritis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Exostosis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Foot deformity † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Fracture pain † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Gouty arthritis † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Haemarthrosis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Intervertebral disc disorder † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Joint effusion † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Lordosis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Lumbar spinal stenosis † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Muscle haemorrhage † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Muscular weakness † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Musculoskeletal chest pain † 1    
# participants affected / at risk     2/1140 (0.18%)     2/1133 (0.18%)  
Musculoskeletal pain † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Neck pain † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Neuropathic arthropathy † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Osteoarthritis † 1    
# participants affected / at risk     7/1140 (0.61%)     7/1133 (0.62%)  
Osteochondrosis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Osteonecrosis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Pain in extremity † 1    
# participants affected / at risk     6/1140 (0.53%)     3/1133 (0.26%)  
Polymyalgia rheumatica † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Rheumatoid arthritis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Spinal column stenosis † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Spinal deformity † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Spinal osteoarthritis † 1    
# participants affected / at risk     0/1140 (0.00%)     3/1133 (0.26%)  
Tenosynovitis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Acute myeloid leukaemia † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Acute myelomonocytic leukaemia † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
B-cell lymphoma † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Bile duct cancer † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Bladder cancer † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Bladder transitional cell carcinoma stage II † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Bone cancer metastatic † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Breast cancer † 1    
# participants affected / at risk     3/1140 (0.26%)     0/1133 (0.00%)  
Breast cancer metastatic † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Bronchial carcinoma † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Carcinoid tumour pulmonary † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Colon adenoma † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Colon cancer † 1    
# participants affected / at risk     5/1140 (0.44%)     2/1133 (0.18%)  
Colon cancer metastatic † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Colon cancer stage III † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Endometrial cancer † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Endometrial sarcoma † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Gastric cancer † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Hepatic neoplasm malignant † 1    
# participants affected / at risk     1/1140 (0.09%)     2/1133 (0.18%)  
Hypopharyngeal cancer † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Laryngeal cancer † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Lipoma † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Lung adenocarcinoma † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Lung neoplasm † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Lung neoplasm malignant † 1    
# participants affected / at risk     1/1140 (0.09%)     5/1133 (0.44%)  
Lymphocytic leukaemia † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Lymphoma † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Malignant anorectal neoplasm † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Malignant neoplasm of ampulla of Vater † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Mantle cell lymphoma † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Meningioma † 1    
# participants affected / at risk     1/1140 (0.09%)     3/1133 (0.26%)  
Mesothelioma malignant † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Metastases to bone † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Metastases to central nervous system † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Metastases to liver † 1    
# participants affected / at risk     6/1140 (0.53%)     2/1133 (0.18%)  
Metastases to peritoneum † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Metastases to spine † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Metastasis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Metastatic bronchial carcinoma † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Metastatic gastric cancer † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Metastatic squamous cell carcinoma † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Multiple myeloma † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Myelodysplastic syndrome † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Neoplasm † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Neoplasm malignant † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Neoplasm prostate † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Non-Hodgkin's lymphoma † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Non-small cell lung cancer metastatic † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Oesophageal adenocarcinoma † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Oesophageal carcinoma † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Ovarian cancer † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Pancreatic carcinoma † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Pituitary tumour benign † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Plasmacytoma † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Prostate cancer † 1    
# participants affected / at risk     8/1140 (0.70%)     3/1133 (0.26%)  
Prostate cancer metastatic † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Rectal cancer † 1    
# participants affected / at risk     2/1140 (0.18%)     2/1133 (0.18%)  
Renal cell carcinoma † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Renal neoplasm † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Salivary gland neoplasm † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Skin papilloma † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Small cell lung cancer stage unspecified † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Small intestine carcinoma † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Squamous cell carcinoma † 1    
# participants affected / at risk     0/1140 (0.00%)     3/1133 (0.26%)  
Tonsillar neoplasm † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Vulval cancer † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Nervous system disorders      
Altered state of consciousness † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Balance disorder † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Brain compression † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Brain oedema † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Carotid artery occlusion † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Carotid artery stenosis † 1    
# participants affected / at risk     0/1140 (0.00%)     3/1133 (0.26%)  
Cerebral haematoma † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Cerebral haemorrhage † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Cerebral infarction † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Cerebral ischaemia † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Cerebrovascular accident † 1    
# participants affected / at risk     14/1140 (1.23%)     27/1133 (2.38%)  
Cerebrovascular insufficiency † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Cervicobrachial syndrome † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Convulsion † 1    
# participants affected / at risk     3/1140 (0.26%)     3/1133 (0.26%)  
Dementia † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Dementia Alzheimer's type † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Diabetic hyperosmolar coma † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Diabetic neuropathy † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Dizziness † 1    
# participants affected / at risk     13/1140 (1.14%)     10/1133 (0.88%)  
Dysarthria † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Encephalopathy † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Epilepsy † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Extrapyramidal disorder † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Haemorrhage intracranial † 1    
# participants affected / at risk     1/1140 (0.09%)     2/1133 (0.18%)  
Haemorrhagic stroke † 1    
# participants affected / at risk     3/1140 (0.26%)     2/1133 (0.18%)  
Headache † 1    
# participants affected / at risk     3/1140 (0.26%)     2/1133 (0.18%)  
Hemiparesis † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Hemiplegia † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Hepatic encephalopathy † 1    
# participants affected / at risk     1/1140 (0.09%)     3/1133 (0.26%)  
Hypoglycaemic coma † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Hypoglycaemic unconsciousness † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Hypoxic-ischaemic encephalopathy † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Intercostal neuralgia † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Ischaemic stroke † 1    
# participants affected / at risk     7/1140 (0.61%)     8/1133 (0.71%)  
Lethargy † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Loss of consciousness † 1    
# participants affected / at risk     3/1140 (0.26%)     6/1133 (0.53%)  
Lumbar radiculopathy † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Mental impairment † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Metabolic encephalopathy † 1    
# participants affected / at risk     3/1140 (0.26%)     1/1133 (0.09%)  
Nerve compression † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Neuropathy peripheral † 1    
# participants affected / at risk     2/1140 (0.18%)     1/1133 (0.09%)  
Paraesthesia † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Presyncope † 1    
# participants affected / at risk     9/1140 (0.79%)     8/1133 (0.71%)  
Radiculopathy † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Somnolence † 1    
# participants affected / at risk     0/1140 (0.00%)     3/1133 (0.26%)  
Spinal cord compression † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Subarachnoid haemorrhage † 1    
# participants affected / at risk     2/1140 (0.18%)     2/1133 (0.18%)  
Syncope † 1    
# participants affected / at risk     29/1140 (2.54%)     19/1133 (1.68%)  
Toxic encephalopathy † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Transient ischaemic attack † 1    
# participants affected / at risk     4/1140 (0.35%)     7/1133 (0.62%)  
VIIth nerve paralysis † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Vocal cord paralysis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Psychiatric disorders      
Anxiety † 1    
# participants affected / at risk     0/1140 (0.00%)     2/1133 (0.18%)  
Confusional state † 1    
# participants affected / at risk     5/1140 (0.44%)     6/1133 (0.53%)  
Delirium † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Depression † 1    
# participants affected / at risk     0/1140 (0.00%)     3/1133 (0.26%)  
Disorientation † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Insomnia † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Major depression † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Mental status changes † 1    
# participants affected / at risk     3/1140 (0.26%)     8/1133 (0.71%)  
Psychiatric symptom † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Restlessness † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Sopor † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Suicidal ideation † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Suicide attempt † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Renal and urinary disorders      
Acute prerenal failure † 1    
# participants affected / at risk     3/1140 (0.26%)     1/1133 (0.09%)  
Anuria † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Azotaemia † 1    
# participants affected / at risk     5/1140 (0.44%)     1/1133 (0.09%)  
Cystitis haemorrhagic † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Dysuria † 1    
# participants affected / at risk     1/1140 (0.09%)     2/1133 (0.18%)  
Haematuria † 1    
# participants affected / at risk     3/1140 (0.26%)     4/1133 (0.35%)  
Hydronephrosis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Ischaemic nephropathy † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Oliguria † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Pollakiuria † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Polyuria † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Renal artery stenosis † 1    
# participants affected / at risk     1/1140 (0.09%)     3/1133 (0.26%)  
Renal failure † 1    
# participants affected / at risk     37/1140 (3.25%)     41/1133 (3.62%)  
Renal failure acute † 1    
# participants affected / at risk     62/1140 (5.44%)     58/1133 (5.12%)  
Renal failure chronic † 1    
# participants affected / at risk     20/1140 (1.75%)     11/1133 (0.97%)  
Renal impairment † 1    
# participants affected / at risk     4/1140 (0.35%)     9/1133 (0.79%)  
Renal injury † 1    
# participants affected / at risk     1/1140 (0.09%)     2/1133 (0.18%)  
Renal mass † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Renal tubular necrosis † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Urethral disorder † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Urethral stenosis † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Urinary bladder haemorrhage † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Urinary retention † 1    
# participants affected / at risk     7/1140 (0.61%)     9/1133 (0.79%)  
Reproductive system and breast disorders      
Benign prostatic hyperplasia † 1    
# participants affected / at risk     2/1140 (0.18%)     2/1133 (0.18%)  
Breast haematoma † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Epididymitis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Menorrhagia † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Pelvic floor muscle weakness † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Prostatic disorder † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Prostatitis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Respiratory, thoracic and mediastinal disorders      
Acute pulmonary oedema † 1    
# participants affected / at risk     8/1140 (0.70%)     5/1133 (0.44%)  
Acute respiratory distress syndrome † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Acute respiratory failure † 1    
# participants affected / at risk     8/1140 (0.70%)     6/1133 (0.53%)  
Asthma † 1    
# participants affected / at risk     4/1140 (0.35%)     1/1133 (0.09%)  
Atelectasis † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Bronchiectasis † 1    
# participants affected / at risk     2/1140 (0.18%)     1/1133 (0.09%)  
Bronchitis chronic † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Bronchospasm † 1    
# participants affected / at risk     2/1140 (0.18%)     0/1133 (0.00%)  
Choking sensation † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Chronic obstructive pulmonary disease † 1    
# participants affected / at risk     42/1140 (3.68%)     22/1133 (1.94%)  
Chronic respiratory failure † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Cough † 1    
# participants affected / at risk     2/1140 (0.18%)     2/1133 (0.18%)  
Dyspnoea † 1    
# participants affected / at risk     29/1140 (2.54%)     27/1133 (2.38%)  
Dyspnoea exertional † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Dyspnoea paroxysmal nocturnal † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Epistaxis † 1    
# participants affected / at risk     4/1140 (0.35%)     3/1133 (0.26%)  
Haemoptysis † 1    
# participants affected / at risk     2/1140 (0.18%)     2/1133 (0.18%)  
Haemothorax † 1    
# participants affected / at risk     1/1140 (0.09%)     1/1133 (0.09%)  
Hypercapnia † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Hypoxia † 1    
# participants affected / at risk     2/1140 (0.18%)     2/1133 (0.18%)  
Lung consolidation † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Pleural effusion † 1    
# participants affected / at risk     9/1140 (0.79%)     11/1133 (0.97%)  
Pleural fibrosis † 1    
# participants affected / at risk     1/1140 (0.09%)     0/1133 (0.00%)  
Pleurisy † 1    
# participants affected / at risk     0/1140 (0.00%)     1/1133 (0.09%)  
Pneumonia aspiration † 1    
# participants affected / at risk     2/1140 (0.18%)     4/1133 (0.35%)  
Pneumonitis