A Trial With Dronedarone to Prevent Hospitalization or Death in Patients With Atrial Fibrillation (ATHENA)

This study has been completed.
Sponsor:
Information provided by:
Sanofi
ClinicalTrials.gov Identifier:
NCT00174785
First received: September 13, 2005
Last updated: January 5, 2010
Last verified: January 2010
Results First Received: July 24, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Prevention
Conditions: Atrial Fibrillation
Atrial Flutter
Interventions: Drug: dronedarone (SR33589)
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
Enrollment of patients started on June 29, 2005 and was completed on December 30, 2006. The study was conducted at 551 centers in 37 countries. The common study end date ensuring a minimum planned follow-up of one year was December 30th, 2007.

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
Dronedarone 400mg Bid dronedarone tablets 400mg twice daily
Placebo matching placebo tablets

Participant Flow:   Overall Study
    Dronedarone 400mg Bid     Placebo  
STARTED     2301 [1]   2327 [2]
COMPLETED     1605 [3]   1611 [3]
NOT COMPLETED     696     716  
Adverse Event                 293                 191  
Protocol Violation                 14                 14  
Withdrawal by Subject                 173                 175  
Atrial Fibrillation/Flutter recurrence                 110                 167  
Prohibited antiarrhythmic medication                 39                 88  
Other prohibited medication                 5                 3  
Family request                 6                 8  
Not pre-specified/Not coded                 56                 70  
[1] randomized patients; among them, 10 patients did not receive any study drug in the dronedarone group
[2] randomized patients; among them, 14 patients did not receive any study drug in the placebo group
[3] completed study drug



  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
Dronedarone 400mg Bid dronedarone tablets 400mg twice daily
Placebo matching placebo tablets
Total Total of all reporting groups

Baseline Measures
    Dronedarone 400mg Bid     Placebo     Total  
Number of Participants  
[units: participants]
  2301     2327     4628  
Age, Customized  
[units: participants]
     
18 to < 65 years     431     442     873  
65 to < 75 years     923     907     1830  
>= 75 years     947     978     1925  
Age  
[units: years]
Mean ± Standard Deviation
  71.6  ± 8.9     71.7  ± 9.0     71.6  ± 9.0  
Gender  
[units: participants]
     
Female     1131     1038     2169  
Male     1170     1289     2459  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   First Hospitalization for Cardiovascular Reason or Death From Any Cause   [ Time Frame: minimum follow-up duration: 1 year ; maximum: 2.5 years ]

2.  Secondary:   Death From Any Cause   [ Time Frame: minimum follow-up duration: 1 year ; maximum: 2.5 years ]

3.  Secondary:   First Hospitalization for Cardiovascular Reason   [ Time Frame: minimum follow-up duration: 1 year ; maximum: 2.5 years ]

4.  Secondary:   Cardiovascular Death   [ Time Frame: minimum follow-up duration: 1 year ; maximum: 2.5 years ]

5.  Other Pre-specified:   Adjudicated Cardiovascular Death   [ Time Frame: minimum follow-up duration: 1 year ; maximum: 2.5 years ]


  Serious Adverse Events
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Time Frame In both treatment groups, the median duration of exposure was about 18 months, with a maximum of 30 months.
Additional Description Reported Events are Treatment-Emergent Adverse Events with an onset date between the first study drug intake and the last study drug intake + 10 days and any pre-treatment adverse event that led to study drug permanent discontinuation.

Reporting Groups
  Description
Dronedarone 400mg Bid dronedarone tablets 400mg twice daily
Placebo matching placebo tablets

Serious Adverse Events
    Dronedarone 400mg Bid     Placebo  
Total, serious adverse events      
# participants affected / at risk     456/2291 (19.90%)     489/2313 (21.14%)  
Blood and lymphatic system disorders      
Anaemia * 1    
# participants affected / at risk     4/2291 (0.17%)     7/2313 (0.30%)  
Splenic infarction * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Anaemia macrocytic * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Anaemia of malignant disease * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Haemorrhagic anaemia * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Leukocytosis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Lymphadenitis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Spontaneous haematoma * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Iron deficiency anaemia * 1    
# participants affected / at risk     0/2291 (0.00%)     4/2313 (0.17%)  
Hypochromic anaemia * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Anaemia haemolytic autoimmune * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Anaemia of chronic disease * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Pancytopenia * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Cardiac disorders      
Bradycardia * 1    
# participants affected / at risk     2/2291 (0.09%)     3/2313 (0.13%)  
Cardiac failure * 1    
# participants affected / at risk     2/2291 (0.09%)     2/2313 (0.09%)  
Pericardial effusion * 1    
# participants affected / at risk     2/2291 (0.09%)     1/2313 (0.04%)  
Ventricular tachycardia * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Acute myocardial infarction * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Angina pectoris * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Cardiac tamponade * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Coronary artery disease * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Pericardial haemorrhage * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Sinus bradycardia * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Torsade de pointes * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Ventricle rupture * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Ventricular extrasystoles * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Cardiac failure congestive * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Angina unstable * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Aortic valve calcification * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Aortic valve incompetence * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Atrioventricular block complete * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Cardiac perforation * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Right ventricular failure * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Ventricular flutter * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Congenital, familial and genetic disorders      
Hydrocele * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Ear and labyrinth disorders      
Vertigo * 1    
# participants affected / at risk     2/2291 (0.09%)     4/2313 (0.17%)  
Vertigo positional * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Hearing impaired * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Inner ear disorder * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Vestibular neuronitis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Endocrine disorders      
Hyperthyroidism * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Goitre * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Hypothyroidism * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Basedow's disease * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Adrenal disorder * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Inappropriate antidiuretic hormone secretion * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Eye disorders      
Cataract * 1    
# participants affected / at risk     4/2291 (0.17%)     3/2313 (0.13%)  
Glaucoma * 1    
# participants affected / at risk     3/2291 (0.13%)     1/2313 (0.04%)  
Open angle glaucoma * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Retinal detachment * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Maculopathy * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Ulcerative keratitis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Blindness * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Endophthalmitis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Myopia * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Ocular retrobulbar haemorrhage * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Optic ischaemic neuropathy * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Pterygium * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Uveitis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Gastrointestinal disorders      
Gastrointestinal haemorrhage * 1    
# participants affected / at risk     6/2291 (0.26%)     5/2313 (0.22%)  
Diarrhoea * 1    
# participants affected / at risk     6/2291 (0.26%)     4/2313 (0.17%)  
Gastritis * 1    
# participants affected / at risk     5/2291 (0.22%)     4/2313 (0.17%)  
Pancreatitis acute * 1    
# participants affected / at risk     4/2291 (0.17%)     3/2313 (0.13%)  
Abdominal pain * 1    
# participants affected / at risk     4/2291 (0.17%)     2/2313 (0.09%)  
Small intestinal obstruction * 1    
# participants affected / at risk     4/2291 (0.17%)     1/2313 (0.04%)  
Inguinal hernia * 1    
# participants affected / at risk     3/2291 (0.13%)     3/2313 (0.13%)  
Colonic polyp * 1    
# participants affected / at risk     3/2291 (0.13%)     1/2313 (0.04%)  
Pancreatitis * 1    
# participants affected / at risk     3/2291 (0.13%)     1/2313 (0.04%)  
Gastrooesophageal reflux disease * 1    
# participants affected / at risk     2/2291 (0.09%)     3/2313 (0.13%)  
Abdominal pain upper * 1    
# participants affected / at risk     2/2291 (0.09%)     2/2313 (0.09%)  
Nausea * 1    
# participants affected / at risk     2/2291 (0.09%)     2/2313 (0.09%)  
Abdominal adhesions * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Abdominal hernia * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Abdominal strangulated hernia * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Constipation * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Crohn's disease * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Gastric haemorrhage * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Haemorrhoidal haemorrhage * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Ileus * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Mallory-weiss syndrome * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Vomiting * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Gastric ulcer * 1    
# participants affected / at risk     1/2291 (0.04%)     3/2313 (0.13%)  
Intestinal obstruction * 1    
# participants affected / at risk     1/2291 (0.04%)     3/2313 (0.13%)  
Rectal haemorrhage * 1    
# participants affected / at risk     1/2291 (0.04%)     3/2313 (0.13%)  
Colitis * 1    
# participants affected / at risk     1/2291 (0.04%)     2/2313 (0.09%)  
Colitis ischaemic * 1    
# participants affected / at risk     1/2291 (0.04%)     2/2313 (0.09%)  
Thrombosis mesenteric vessel * 1    
# participants affected / at risk     1/2291 (0.04%)     2/2313 (0.09%)  
Oesophagitis * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Anal prolapse * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Diverticulum intestinal haemorrhagic * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Duodenal ulcer * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Dyspepsia * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Femoral hernia, obstructive * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Food poisoning * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Gastritis erosive * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Gastritis haemorrhagic * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Gastroduodenitis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Ileus paralytic * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Infrequent bowel movements * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Intestinal fistula * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Lumbar hernia * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Mouth haemorrhage * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Oesophageal mass * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Oesophageal spasm * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Oesophagitis ulcerative * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Peritonitis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Reflux oesophagitis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Toothache * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Upper gastrointestinal haemorrhage * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Appendicitis perforated * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Diverticulum * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Dysphagia * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Gastric ulcer haemorrhage * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Lower gastrointestinal haemorrhage * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Colitis ulcerative * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Diverticular perforation * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Diverticulum intestinal * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Duodenal ulcer haemorrhage * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Gastric polyps * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Haematemesis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Haematochezia * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Haemorrhoids * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Hiatus hernia, obstructive * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Intestinal haemorrhage * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Intussusception * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Irritable bowel syndrome * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Mesenteric artery thrombosis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Mesenteric occlusion * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Oedematous pancreatitis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Peptic ulcer haemorrhage * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Short-bowel syndrome * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Umbilical hernia * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
General disorders      
Non-cardiac chest pain * 1    
# participants affected / at risk     4/2291 (0.17%)     3/2313 (0.13%)  
Asthenia * 1    
# participants affected / at risk     3/2291 (0.13%)     3/2313 (0.13%)  
Pyrexia * 1    
# participants affected / at risk     2/2291 (0.09%)     2/2313 (0.09%)  
General physical health deterioration * 1    
# participants affected / at risk     1/2291 (0.04%)     2/2313 (0.09%)  
Drowning * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Oedema * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Oedema peripheral * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Multi-organ failure * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Hernia * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Impaired healing * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Implant site haematoma * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Injection site haematoma * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Hepatobiliary disorders      
Cholecystitis acute * 1    
# participants affected / at risk     6/2291 (0.26%)     5/2313 (0.22%)  
Cholecystitis * 1    
# participants affected / at risk     6/2291 (0.26%)     4/2313 (0.17%)  
Cholangitis * 1    
# participants affected / at risk     4/2291 (0.17%)     0/2313 (0.00%)  
Cholelithiasis * 1    
# participants affected / at risk     3/2291 (0.13%)     7/2313 (0.30%)  
Bile duct stone * 1    
# participants affected / at risk     2/2291 (0.09%)     1/2313 (0.04%)  
Biliary colic * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Cholecystitis chronic * 1    
# participants affected / at risk     1/2291 (0.04%)     2/2313 (0.09%)  
Hepatitis toxic * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Jaundice * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Hepatic cirrhosis * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Cholestasis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Cytolytic hepatitis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Immune system disorders      
Hypersensitivity * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Sarcoidosis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Infections and infestations      
Pneumonia * 1    
# participants affected / at risk     32/2291 (1.40%)     45/2313 (1.95%)  
Urinary tract infection * 1    
# participants affected / at risk     6/2291 (0.26%)     10/2313 (0.43%)  
Cellulitis * 1    
# participants affected / at risk     5/2291 (0.22%)     7/2313 (0.30%)  
Gastroenteritis * 1    
# participants affected / at risk     5/2291 (0.22%)     6/2313 (0.26%)  
Lobar pneumonia * 1    
# participants affected / at risk     5/2291 (0.22%)     6/2313 (0.26%)  
Diverticulitis * 1    
# participants affected / at risk     4/2291 (0.17%)     4/2313 (0.17%)  
Bronchitis * 1    
# participants affected / at risk     4/2291 (0.17%)     3/2313 (0.13%)  
Appendicitis * 1    
# participants affected / at risk     4/2291 (0.17%)     2/2313 (0.09%)  
Bronchopneumonia * 1    
# participants affected / at risk     4/2291 (0.17%)     2/2313 (0.09%)  
Sepsis * 1    
# participants affected / at risk     3/2291 (0.13%)     3/2313 (0.13%)  
Urosepsis * 1    
# participants affected / at risk     2/2291 (0.09%)     4/2313 (0.17%)  
Pyelonephritis chronic * 1    
# participants affected / at risk     2/2291 (0.09%)     2/2313 (0.09%)  
Herpes zoster * 1    
# participants affected / at risk     2/2291 (0.09%)     1/2313 (0.04%)  
Pyelonephritis * 1    
# participants affected / at risk     2/2291 (0.09%)     1/2313 (0.04%)  
Bronchiectasis * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Mastitis * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Respiratory tract infection viral * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Septic shock * 1    
# participants affected / at risk     1/2291 (0.04%)     4/2313 (0.17%)  
Upper respiratory tract infection * 1    
# participants affected / at risk     1/2291 (0.04%)     3/2313 (0.13%)  
Viral infection * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Abscess * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Abscess limb * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Abscess oral * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Acarodermatitis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Clonorchiasis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Diarrhoea infectious * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Encephalitis viral * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Epstein-barr virus infection * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Escherichia sepsis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Gastroenteritis viral * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Hepatitis a * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Infected epidermal cyst * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Infection * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Influenza * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Localised infection * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Opisthorchiasis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Orchitis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Osteomyelitis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Osteomyelitis chronic * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Pancreatitis viral * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Peritoneal infection * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Pneumonia bacterial * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Pneumonia klebsiella * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Rectal abscess * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Respiratory tract infection * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Skin infection * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Soft tissue infection * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Wound infection bacterial * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Erysipelas * 1    
# participants affected / at risk     0/2291 (0.00%)     4/2313 (0.17%)  
Device related infection * 1    
# participants affected / at risk     0/2291 (0.00%)     3/2313 (0.13%)  
Sinusitis * 1    
# participants affected / at risk     0/2291 (0.00%)     3/2313 (0.13%)  
Clostridium difficile colitis * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Obstructive chronic bronchitis with acute exacerbation * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Postoperative wound infection * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Pyelonephritis acute * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Abdominal abscess * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Bacteraemia * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Bursitis infective * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Diabetic gangrene * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Gastroenteritis salmonella * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Groin infection * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Hiv infection * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Infective exacerbation of chronic obstructive airways disease * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Labyrinthitis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Lower respiratory tract infection * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Paronychia * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Peridiverticular abscess * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Peritonsillar abscess * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Pneumonia legionella * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Pneumonia pneumococcal * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Pneumonia staphylococcal * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Post procedural infection * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Pyothorax * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Staphylococcal infection * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Staphylococcal sepsis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Tinea cruris * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Tracheobronchitis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Injury, poisoning and procedural complications      
Fall * 1    
# participants affected / at risk     20/2291 (0.87%)     20/2313 (0.86%)  
Hip fracture * 1    
# participants affected / at risk     5/2291 (0.22%)     2/2313 (0.09%)  
Road traffic accident * 1    
# participants affected / at risk     3/2291 (0.13%)     3/2313 (0.13%)  
Contusion * 1    
# participants affected / at risk     3/2291 (0.13%)     2/2313 (0.09%)  
Femoral neck fracture * 1    
# participants affected / at risk     3/2291 (0.13%)     0/2313 (0.00%)  
Therapeutic agent toxicity * 1    
# participants affected / at risk     3/2291 (0.13%)     0/2313 (0.00%)  
Tendon rupture * 1    
# participants affected / at risk     2/2291 (0.09%)     2/2313 (0.09%)  
Accidental overdose * 1    
# participants affected / at risk     2/2291 (0.09%)     1/2313 (0.04%)  
Femur fracture * 1    
# participants affected / at risk     2/2291 (0.09%)     1/2313 (0.04%)  
Rib fracture * 1    
# participants affected / at risk     2/2291 (0.09%)     1/2313 (0.04%)  
Alcohol poisoning * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Lower limb fracture * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Spinal compression fracture * 1    
# participants affected / at risk     1/2291 (0.04%)     4/2313 (0.17%)  
Humerus fracture * 1    
# participants affected / at risk     1/2291 (0.04%)     3/2313 (0.13%)  
Traumatic haematoma * 1    
# participants affected / at risk     1/2291 (0.04%)     3/2313 (0.13%)  
Brain contusion * 1    
# participants affected / at risk     1/2291 (0.04%)     2/2313 (0.09%)  
Lumbar vertebral fracture * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Post procedural haematoma * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Post-traumatic pain * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Pubic rami fracture * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Skull fracture * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Subdural haematoma * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Traumatic arthritis * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Acetabulum fracture * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Anaemia postoperative * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Anastomotic complication * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Asbestosis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Cervical vertebral fracture * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Device failure * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Foot fracture * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Head injury * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Incisional hernia * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Joint injury * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Medical device pain * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Patella fracture * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Post procedural haemorrhage * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Postoperative heterotopic calcification * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Transfusion reaction * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Dislocation of joint prosthesis * 1    
# participants affected / at risk     0/2291 (0.00%)     5/2313 (0.22%)  
Ankle fracture * 1    
# participants affected / at risk     0/2291 (0.00%)     3/2313 (0.13%)  
Arterial injury * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Concussion * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Device migration * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Facial bones fracture * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Fibula fracture * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Graft thrombosis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Hand fracture * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Injury * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Joint dislocation * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Muscle injury * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Operative haemorrhage * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Overdose * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Pelvic fracture * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Penetrating abdominal trauma * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Procedural pain * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Spinal cord injury cervical * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Traumatic arthropathy * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Investigations      
Blood creatinine increased * 1    
# participants affected / at risk     5/2291 (0.22%)     1/2313 (0.04%)  
International normalised ratio increased * 1    
# participants affected / at risk     4/2291 (0.17%)     6/2313 (0.26%)  
Electrocardiogram qt prolonged * 1    
# participants affected / at risk     4/2291 (0.17%)     1/2313 (0.04%)  
Weight decreased * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Cardioactive drug level increased * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Coagulation test abnormal * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
International normalised ratio decreased * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Prothrombin time prolonged * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Alanine aminotransferase increased * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Aspartate aminotransferase increased * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Blood creatine phosphokinase increased * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Glycosylated haemoglobin increased * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Hepatitis c positive * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Transaminases increased * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Metabolism and nutrition disorders      
Dehydration * 1    
# participants affected / at risk     4/2291 (0.17%)     10/2313 (0.43%)  
Diabetes mellitus * 1    
# participants affected / at risk     4/2291 (0.17%)     3/2313 (0.13%)  
Hypoglycaemia * 1    
# participants affected / at risk     3/2291 (0.13%)     3/2313 (0.13%)  
Hyponatraemia * 1    
# participants affected / at risk     3/2291 (0.13%)     2/2313 (0.09%)  
Hypokalaemia * 1    
# participants affected / at risk     2/2291 (0.09%)     3/2313 (0.13%)  
Gout * 1    
# participants affected / at risk     1/2291 (0.04%)     2/2313 (0.09%)  
Anorexia * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Hyperglycaemia * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Hyperkalaemia * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Fluid overload * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Metabolic acidosis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Vitamin b12 deficiency * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Failure to thrive * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Type 2 diabetes mellitus * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Musculoskeletal and connective tissue disorders      
Osteoarthritis * 1    
# participants affected / at risk     15/2291 (0.65%)     21/2313 (0.91%)  
Arthralgia * 1    
# participants affected / at risk     4/2291 (0.17%)     2/2313 (0.09%)  
Musculoskeletal chest pain * 1    
# participants affected / at risk     2/2291 (0.09%)     2/2313 (0.09%)  
Intervertebral disc protrusion * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Back pain * 1    
# participants affected / at risk     1/2291 (0.04%)     5/2313 (0.22%)  
Muscular weakness * 1    
# participants affected / at risk     1/2291 (0.04%)     4/2313 (0.17%)  
Rotator cuff syndrome * 1    
# participants affected / at risk     1/2291 (0.04%)     4/2313 (0.17%)  
Pain in extremity * 1    
# participants affected / at risk     1/2291 (0.04%)     3/2313 (0.13%)  
Lumbar spinal stenosis * 1    
# participants affected / at risk     1/2291 (0.04%)     2/2313 (0.09%)  
Rheumatoid arthritis * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Arthropathy * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Bursitis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Dupuytren's contracture * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Gouty arthritis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Joint swelling * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Muscle spasms * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Spondylolisthesis acquired * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Sympathetic posterior cervical syndrome * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Haemarthrosis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Intervertebral disc compression * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Neck mass * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Osteonecrosis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Osteoporotic fracture * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Pathological fracture * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Polyarthritis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Polymyalgia rheumatica * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Rhabdomyolysis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Spondylolysis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Prostate cancer * 1    
# participants affected / at risk     6/2291 (0.26%)     11/2313 (0.48%)  
Colon cancer * 1    
# participants affected / at risk     5/2291 (0.22%)     5/2313 (0.22%)  
Breast cancer * 1    
# participants affected / at risk     3/2291 (0.13%)     5/2313 (0.22%)  
Basal cell carcinoma * 1    
# participants affected / at risk     2/2291 (0.09%)     3/2313 (0.13%)  
Lung neoplasm malignant * 1    
# participants affected / at risk     2/2291 (0.09%)     2/2313 (0.09%)  
B-cell lymphoma * 1    
# participants affected / at risk     2/2291 (0.09%)     1/2313 (0.04%)  
Oesophageal adenocarcinoma * 1    
# participants affected / at risk     2/2291 (0.09%)     1/2313 (0.04%)  
Pancreatic carcinoma * 1    
# participants affected / at risk     2/2291 (0.09%)     1/2313 (0.04%)  
Renal cell carcinoma stage unspecified * 1    
# participants affected / at risk     2/2291 (0.09%)     1/2313 (0.04%)  
Squamous cell carcinoma * 1    
# participants affected / at risk     2/2291 (0.09%)     1/2313 (0.04%)  
Bladder neoplasm * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Uterine cancer * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Bladder cancer * 1    
# participants affected / at risk     1/2291 (0.04%)     3/2313 (0.13%)  
Lung adenocarcinoma * 1    
# participants affected / at risk     1/2291 (0.04%)     2/2313 (0.09%)  
Lung squamous cell carcinoma stage unspecified * 1    
# participants affected / at risk     1/2291 (0.04%)     2/2313 (0.09%)  
Malignant melanoma * 1    
# participants affected / at risk     1/2291 (0.04%)     2/2313 (0.09%)  
Non-small cell lung cancer * 1    
# participants affected / at risk     1/2291 (0.04%)     2/2313 (0.09%)  
Prostatic adenoma * 1    
# participants affected / at risk     1/2291 (0.04%)     2/2313 (0.09%)  
Hepatic neoplasm malignant * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Lung adenocarcinoma metastatic * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Non-small cell lung cancer metastatic * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Rectal cancer * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Acute myeloid leukaemia * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Benign neoplasm of thyroid gland * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Bladder papilloma * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Bladder transitional cell carcinoma * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Brain neoplasm * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Bronchioloalveolar carcinoma * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Carcinoid tumour pulmonary * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Colon adenoma * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Endometrial cancer * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Hepatic neoplasm * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Leiomyosarcoma metastatic * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Lung cancer metastatic * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Metastases to lung * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Metastasis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Metastatic carcinoma of the bladder * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Multiple myeloma * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Myeloproliferative disorder * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Nasal cavity cancer * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Oesophageal cancer metastatic * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Pancreatic neoplasm * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Rectal neoplasm * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Squamous cell carcinoma of skin * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Thymoma malignant * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Urethral adenoma * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Ovarian adenoma * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Prostate cancer metastatic * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Adrenal adenoma * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Benign peritoneal neoplasm * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Breast cancer recurrent * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Breast cancer stage iii * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Bronchial carcinoma * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Colorectal cancer * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Gastric cancer * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Glioblastoma * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Inflammatory carcinoma of the breast * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Large intestine carcinoma * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Lip and/or oral cavity cancer * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Lung neoplasm * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Lymphoma * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Malignant pleural effusion * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Metastases to liver * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Myelodysplastic syndrome * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Ocular neoplasm * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Ovarian cancer * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Papillary serous endometrial carcinoma * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Pituitary tumour benign * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Plasmacytoma * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Pleura carcinoma * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Renal neoplasm * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Small cell lung cancer metastatic * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Small cell lung cancer stage unspecified * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Tumour ulceration * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Vulval cancer * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Nervous system disorders      
Dizziness * 1    
# participants affected / at risk     3/2291 (0.13%)     2/2313 (0.09%)  
Transient ischaemic attack * 1    
# participants affected / at risk     2/2291 (0.09%)     2/2313 (0.09%)  
Dementia alzheimer's type * 1    
# participants affected / at risk     2/2291 (0.09%)     1/2313 (0.04%)  
Ischaemic stroke * 1    
# participants affected / at risk     2/2291 (0.09%)     1/2313 (0.04%)  
Sciatica * 1    
# participants affected / at risk     2/2291 (0.09%)     1/2313 (0.04%)  
Syncope * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Brain mass * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Cerebrovascular disorder * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Headache * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Intracranial aneurysm * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Lumbar radiculopathy * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Pseudobulbar palsy * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Spinal claudication * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Vascular encephalopathy * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Vertebrobasilar insufficiency * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Carpal tunnel syndrome * 1    
# participants affected / at risk     0/2291 (0.00%)     3/2313 (0.13%)  
Cerebrovascular accident * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Partial seizures * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Amyotrophic lateral sclerosis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Convulsion * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Diplegia * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Epilepsy * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Facial palsy * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Guillain-barre syndrome * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Haemorrhagic stroke * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Hepatic encephalopathy * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Loss of consciousness * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Metabolic encephalopathy * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Mononeuritis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Toxic encephalopathy * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Psychiatric disorders      
Depression * 1    
# participants affected / at risk     3/2291 (0.13%)     1/2313 (0.04%)  
Mental status changes * 1    
# participants affected / at risk     1/2291 (0.04%)     3/2313 (0.13%)  
Generalised anxiety disorder * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Major depression * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Anxiety * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Alcohol withdrawal syndrome * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Alcoholism * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Confusional state * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Delirium tremens * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Post-traumatic stress disorder * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Suicide attempt * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Renal and urinary disorders      
Renal failure acute * 1    
# participants affected / at risk     14/2291 (0.61%)     4/2313 (0.17%)  
Haematuria * 1    
# participants affected / at risk     7/2291 (0.31%)     7/2313 (0.30%)  
Calculus urinary * 1    
# participants affected / at risk     2/2291 (0.09%)     2/2313 (0.09%)  
Nephrolithiasis * 1    
# participants affected / at risk     2/2291 (0.09%)     2/2313 (0.09%)  
Diabetic nephropathy * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Hydronephrosis * 1    
# participants affected / at risk     1/2291 (0.04%)     2/2313 (0.09%)  
Urinary retention * 1    
# participants affected / at risk     1/2291 (0.04%)     2/2313 (0.09%)  
Renal colic * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Renal failure * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Renal failure chronic * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Calculus bladder * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Nocturia * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Renal impairment * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Urinary bladder polyp * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Bladder obstruction * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Cystitis haemorrhagic * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Cystitis noninfective * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Stress urinary incontinence * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Urethral stenosis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Reproductive system and breast disorders      
Benign prostatic hyperplasia * 1    
# participants affected / at risk     8/2291 (0.35%)     10/2313 (0.43%)  
Uterine polyp * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Acquired hydrocele * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Breast discomfort * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Endometrial hyperplasia * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Penis disorder * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Uterine prolapse * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Prostatitis * 1    
# participants affected / at risk     0/2291 (0.00%)     3/2313 (0.13%)  
Vaginal prolapse * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Adnexa uteri cyst * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Epididymitis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Gynaecomastia * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Respiratory, thoracic and mediastinal disorders      
Chronic obstructive pulmonary disease * 1    
# participants affected / at risk     13/2291 (0.57%)     19/2313 (0.82%)  
Asthma * 1    
# participants affected / at risk     5/2291 (0.22%)     2/2313 (0.09%)  
Respiratory failure * 1    
# participants affected / at risk     4/2291 (0.17%)     1/2313 (0.04%)  
Pleural effusion * 1    
# participants affected / at risk     3/2291 (0.13%)     4/2313 (0.17%)  
Pleurisy * 1    
# participants affected / at risk     3/2291 (0.13%)     0/2313 (0.00%)  
Haemoptysis * 1    
# participants affected / at risk     2/2291 (0.09%)     3/2313 (0.13%)  
Interstitial lung disease * 1    
# participants affected / at risk     2/2291 (0.09%)     1/2313 (0.04%)  
Epistaxis * 1    
# participants affected / at risk     1/2291 (0.04%)     4/2313 (0.17%)  
Dyspnoea * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Hypoxia * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Pulmonary fibrosis * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Acute respiratory failure * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Emphysema * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Lung disorder * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Nasal turbinate hypertrophy * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Obstructive airways disorder * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Pneumonitis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Sleep apnoea syndrome * 1    
# participants affected / at risk     0/2291 (0.00%)     3/2313 (0.13%)  
Pneumonia aspiration * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Bronchopneumopathy * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Cough * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Nasal polyps * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Pulmonary mass * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Pulmonary oedema * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Skin and subcutaneous tissue disorders      
Skin ulcer * 1    
# participants affected / at risk     2/2291 (0.09%)     0/2313 (0.00%)  
Panniculitis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Pemphigoid * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Photodermatosis * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Pruritus * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Urticaria * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Rash * 1    
# participants affected / at risk     0/2291 (0.00%)     2/2313 (0.09%)  
Decubitus ulcer * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Dermatitis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Dermatitis bullous * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Psoriasis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Social circumstances      
Victim of crime * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Surgical and medical procedures      
Ileostomy closure * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Shoulder arthroplasty * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Suprapubic catheter insertion * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Transurethral prostatectomy * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Hip arthroplasty * 1    
# participants affected / at risk     0/2291 (0.00%)     3/2313 (0.13%)  
Knee operation * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Pilonidal sinus repair * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Vascular disorders      
Haematoma * 1    
# participants affected / at risk     3/2291 (0.13%)     3/2313 (0.13%)  
Aortic aneurysm * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Femoral arterial stenosis * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Haemorrhage * 1    
# participants affected / at risk     1/2291 (0.04%)     1/2313 (0.04%)  
Hypovolaemic shock * 1    
# participants affected / at risk     1/2291 (0.04%)     0/2313 (0.00%)  
Angiodysplasia * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Iliac artery embolism * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Lymphoedema * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Peripheral embolism * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Thrombophlebitis * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
Varicose vein * 1    
# participants affected / at risk     0/2291 (0.00%)     1/2313 (0.04%)  
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA (10.1)




  Other Adverse Events


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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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