Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 40 of 78 for:    sanofi-aventis and sweden

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00174785
Recruitment Status : Completed
First Posted : September 15, 2005
Results First Posted : December 23, 2009
Last Update Posted : January 12, 2010
Sponsor:
Information provided by:
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Conditions Atrial Fibrillation
Atrial Flutter
Interventions Drug: dronedarone (SR33589)
Drug: placebo
Enrollment 4628
Recruitment Details 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  
Arm/Group Title Dronedarone 400mg Bid Placebo
Hide Arm/Group Description dronedarone tablets 400mg twice daily matching placebo tablets
Period Title: Overall Study
Started 2301 [1] 2327 [2]
Completed 1605 [3] 1611 [3]
Not Completed 696 716
Reason Not Completed
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
Arm/Group Title Dronedarone 400mg Bid Placebo Total
Hide Arm/Group Description dronedarone tablets 400mg twice daily matching placebo tablets Total of all reporting groups
Overall Number of Baseline Participants 2301 2327 4628
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 2301 participants 2327 participants 4628 participants
18 to < 65 years 431 442 873
65 to < 75 years 923 907 1830
>= 75 years 947 978 1925
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2301 participants 2327 participants 4628 participants
71.6  (8.9) 71.7  (9.0) 71.6  (9.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2301 participants 2327 participants 4628 participants
Female
1131
  49.2%
1038
  44.6%
2169
  46.9%
Male
1170
  50.8%
1289
  55.4%
2459
  53.1%
1.Primary Outcome
Title First Hospitalization for Cardiovascular Reason or Death From Any Cause
Hide Description The primary event is the first hospitalization for cardiovascular reason or death from any cause, whichever is earlier, as assessed by the investigator. The primary efficacy analysis is performed on the time from randomization to this primary event. The Measured Values table below presents the numbers of patients with the event at the end of the study period.
Time Frame minimum follow-up duration: 1 year ; maximum: 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were performed on the "all randomized patients" population including all patients randomized irrespective of whether the patient actually received any drug or complied with the study protocol.
Arm/Group Title Dronedarone 400mg Bid Placebo
Hide Arm/Group Description:
dronedarone tablets 400mg twice daily
matching placebo tablets
Overall Number of Participants Analyzed 2301 2327
Measure Type: Number
Unit of Measure: participants
734 917
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dronedarone 400mg Bid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Cumulative incidence functions in each treatment group were calculated using non-parametric Kaplan-Meier estimates. Median time-to-event was not reached in any group. The primary comparison was performed at the 5% level using a 2-sided Log rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.76
Confidence Interval 95%
0.69 to 0.84
Estimation Comments The hazard ratio was estimated by a Cox's proportional hazard model with treatment arm factor. It represents the relative hazard of first hospitalization for cardiovascular reason or death for the dronedarone group compared with the placebo group.
2.Secondary Outcome
Title Death From Any Cause
Hide Description The considered event is death from any cause. The analysis is performed on the time from randomization to this event. The Measured Values table below presents the numbers of patients with the event at the end of the study period.
Time Frame minimum follow-up duration: 1 year ; maximum: 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
«All randomized patients» population
Arm/Group Title Dronedarone 400mg Bid Placebo
Hide Arm/Group Description:
dronedarone tablets 400mg twice daily
matching placebo tablets
Overall Number of Participants Analyzed 2301 2327
Measure Type: Number
Unit of Measure: participants
116 139
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dronedarone 400mg Bid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.18
Comments Cumulative incidences calculated in each group using non-parametric Kaplan-Meier estimates. Median time-to-event was not reached in any group. Hierarchical procedure applied to secondary efficacy endpoints testing to protect the global type I error.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.84
Confidence Interval 95%
0.66 to 1.08
Estimation Comments The hazard ratio was estimated by a Cox's proportional hazard model with treatment arm factor. It represents the relative hazard of death from any cause for the dronedarone group compared with the placebo group.
3.Secondary Outcome
Title First Hospitalization for Cardiovascular Reason
Hide Description The considered event is the first hospitalization for cardiovascular reason, as assessed by the Investigator. The analysis is performed on the time from randomization to this event. The Measured Values table below presents the numbers of patients with the event at the end of the study period.
Time Frame minimum follow-up duration: 1 year ; maximum: 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
«All randomized patients» population
Arm/Group Title Dronedarone 400mg Bid Placebo
Hide Arm/Group Description:
dronedarone tablets 400mg twice daily
matching placebo tablets
Overall Number of Participants Analyzed 2301 2327
Measure Type: Number
Unit of Measure: participants
675 859
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dronedarone 400mg Bid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Cumulative incidences calculated in each group using non-parametric Kaplan-Meier estimates. Median time-to-event was not reached in any group. Hierarchical procedure applied to secondary efficacy endpoints testing to protect the global type I error.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval 95%
0.67 to 0.82
Estimation Comments The hazard ratio was estimated by a Cox's proportional hazard model with treatment arm factor. It represents the relative hazard of first hospitalization for cardiovascular reason for the dronedarone group compared with the placebo group.
4.Secondary Outcome
Title Cardiovascular Death
Hide Description The considered event is cardiovascular death, as assessed by the Investigator. The analysis is performed on the time from randomization to this event. The Measured Values table below presents the numbers of patients with the event at the end of the study period.
Time Frame minimum follow-up duration: 1 year ; maximum: 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
«All randomized patients» population
Arm/Group Title Dronedarone 400mg Bid Placebo
Hide Arm/Group Description:
dronedarone tablets 400mg twice daily
matching placebo tablets
Overall Number of Participants Analyzed 2301 2327
Measure Type: Number
Unit of Measure: participants
65 94
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dronedarone 400mg Bid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.025
Comments Cumulative incidences calculated in each group using non-parametric Kaplan-Meier estimates. Median time-to-event was not reached in any group. Hierarchical procedure applied to secondary efficacy endpoints testing to protect the global type I error.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.70
Confidence Interval 95%
0.51 to 0.96
Estimation Comments The hazard ratio was estimated by a Cox's proportional hazard model with treatment arm factor. It represents the relative hazard of cardiovascular death for the dronedarone group compared with the placebo group.
5.Other Pre-specified Outcome
Title Adjudicated Cardiovascular Death
Hide Description The considered event is cardiovascular death, as assessed by the blinded adjudication of the Steering Committee. The analysis is performed on the time from randomization to this event. The Measured Values table below presents the numbers of patients with the event at the end of the study period.
Time Frame minimum follow-up duration: 1 year ; maximum: 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
«All randomized patients» population
Arm/Group Title Dronedarone 400mg Bid Placebo
Hide Arm/Group Description:
dronedarone tablets 400mg twice daily
matching placebo tablets
Overall Number of Participants Analyzed 2301 2327
Measure Type: Number
Unit of Measure: participants
63 90
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dronedarone 400mg Bid, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments Cumulative incidences calculated in each group using non-parametric Kaplan-Meier estimates. Median time-to-event was not reached in any group. The comparison was performed at the 5% level using a 2-sided Log rank
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.71
Confidence Interval 95%
0.51 to 0.98
Estimation Comments The hazard ratio was estimated by a Cox's proportional hazard model with treatment arm factor. It represents the relative hazard of adjudicated cardiovascular death for the dronedarone group compared with the placebo group.
Time Frame In both treatment groups, the median duration of exposure was about 18 months, with a maximum of 30 months.
Adverse Event Reporting 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.
 
Arm/Group Title Dronedarone 400mg Bid Placebo
Hide Arm/Group Description dronedarone tablets 400mg twice daily matching placebo tablets
All-Cause Mortality
Dronedarone 400mg Bid Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Dronedarone 400mg Bid Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   456/2291 (19.90%)   489/2313 (21.14%) 
Blood and lymphatic system disorders     
Anaemia * 1  4/2291 (0.17%)  7/2313 (0.30%) 
Splenic infarction * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Anaemia macrocytic * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Anaemia of malignant disease * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Haemorrhagic anaemia * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Leukocytosis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Lymphadenitis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Spontaneous haematoma * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Iron deficiency anaemia * 1  0/2291 (0.00%)  4/2313 (0.17%) 
Hypochromic anaemia * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Anaemia haemolytic autoimmune * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Anaemia of chronic disease * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Pancytopenia * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Cardiac disorders     
Bradycardia * 1  2/2291 (0.09%)  3/2313 (0.13%) 
Cardiac failure * 1  2/2291 (0.09%)  2/2313 (0.09%) 
Pericardial effusion * 1  2/2291 (0.09%)  1/2313 (0.04%) 
Ventricular tachycardia * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Acute myocardial infarction * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Angina pectoris * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Cardiac tamponade * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Coronary artery disease * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Pericardial haemorrhage * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Sinus bradycardia * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Torsade de pointes * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Ventricle rupture * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Ventricular extrasystoles * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Cardiac failure congestive * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Angina unstable * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Aortic valve calcification * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Aortic valve incompetence * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Atrioventricular block complete * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Cardiac perforation * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Right ventricular failure * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Ventricular flutter * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Congenital, familial and genetic disorders     
Hydrocele * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Ear and labyrinth disorders     
Vertigo * 1  2/2291 (0.09%)  4/2313 (0.17%) 
Vertigo positional * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Hearing impaired * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Inner ear disorder * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Vestibular neuronitis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Endocrine disorders     
Hyperthyroidism * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Goitre * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Hypothyroidism * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Basedow's disease * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Adrenal disorder * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Inappropriate antidiuretic hormone secretion * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Eye disorders     
Cataract * 1  4/2291 (0.17%)  3/2313 (0.13%) 
Glaucoma * 1  3/2291 (0.13%)  1/2313 (0.04%) 
Open angle glaucoma * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Retinal detachment * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Maculopathy * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Ulcerative keratitis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Blindness * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Endophthalmitis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Myopia * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Ocular retrobulbar haemorrhage * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Optic ischaemic neuropathy * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Pterygium * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Uveitis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Gastrointestinal disorders     
Gastrointestinal haemorrhage * 1  6/2291 (0.26%)  5/2313 (0.22%) 
Diarrhoea * 1  6/2291 (0.26%)  4/2313 (0.17%) 
Gastritis * 1  5/2291 (0.22%)  4/2313 (0.17%) 
Pancreatitis acute * 1  4/2291 (0.17%)  3/2313 (0.13%) 
Abdominal pain * 1  4/2291 (0.17%)  2/2313 (0.09%) 
Small intestinal obstruction * 1  4/2291 (0.17%)  1/2313 (0.04%) 
Inguinal hernia * 1  3/2291 (0.13%)  3/2313 (0.13%) 
Colonic polyp * 1  3/2291 (0.13%)  1/2313 (0.04%) 
Pancreatitis * 1  3/2291 (0.13%)  1/2313 (0.04%) 
Gastrooesophageal reflux disease * 1  2/2291 (0.09%)  3/2313 (0.13%) 
Abdominal pain upper * 1  2/2291 (0.09%)  2/2313 (0.09%) 
Nausea * 1  2/2291 (0.09%)  2/2313 (0.09%) 
Abdominal adhesions * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Abdominal hernia * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Abdominal strangulated hernia * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Constipation * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Crohn's disease * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Gastric haemorrhage * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Haemorrhoidal haemorrhage * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Ileus * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Mallory-weiss syndrome * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Vomiting * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Gastric ulcer * 1  1/2291 (0.04%)  3/2313 (0.13%) 
Intestinal obstruction * 1  1/2291 (0.04%)  3/2313 (0.13%) 
Rectal haemorrhage * 1  1/2291 (0.04%)  3/2313 (0.13%) 
Colitis * 1  1/2291 (0.04%)  2/2313 (0.09%) 
Colitis ischaemic * 1  1/2291 (0.04%)  2/2313 (0.09%) 
Thrombosis mesenteric vessel * 1  1/2291 (0.04%)  2/2313 (0.09%) 
Oesophagitis * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Anal prolapse * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Diverticulum intestinal haemorrhagic * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Duodenal ulcer * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Dyspepsia * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Femoral hernia, obstructive * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Food poisoning * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Gastritis erosive * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Gastritis haemorrhagic * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Gastroduodenitis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Ileus paralytic * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Infrequent bowel movements * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Intestinal fistula * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Lumbar hernia * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Mouth haemorrhage * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Oesophageal mass * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Oesophageal spasm * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Oesophagitis ulcerative * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Peritonitis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Reflux oesophagitis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Toothache * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Upper gastrointestinal haemorrhage * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Appendicitis perforated * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Diverticulum * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Dysphagia * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Gastric ulcer haemorrhage * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Lower gastrointestinal haemorrhage * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Colitis ulcerative * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Diverticular perforation * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Diverticulum intestinal * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Duodenal ulcer haemorrhage * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Gastric polyps * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Haematemesis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Haematochezia * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Haemorrhoids * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Hiatus hernia, obstructive * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Intestinal haemorrhage * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Intussusception * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Irritable bowel syndrome * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Mesenteric artery thrombosis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Mesenteric occlusion * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Oedematous pancreatitis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Peptic ulcer haemorrhage * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Short-bowel syndrome * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Umbilical hernia * 1  0/2291 (0.00%)  1/2313 (0.04%) 
General disorders     
Non-cardiac chest pain * 1  4/2291 (0.17%)  3/2313 (0.13%) 
Asthenia * 1  3/2291 (0.13%)  3/2313 (0.13%) 
Pyrexia * 1  2/2291 (0.09%)  2/2313 (0.09%) 
General physical health deterioration * 1  1/2291 (0.04%)  2/2313 (0.09%) 
Drowning * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Oedema * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Oedema peripheral * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Multi-organ failure * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Hernia * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Impaired healing * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Implant site haematoma * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Injection site haematoma * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Hepatobiliary disorders     
Cholecystitis acute * 1  6/2291 (0.26%)  5/2313 (0.22%) 
Cholecystitis * 1  6/2291 (0.26%)  4/2313 (0.17%) 
Cholangitis * 1  4/2291 (0.17%)  0/2313 (0.00%) 
Cholelithiasis * 1  3/2291 (0.13%)  7/2313 (0.30%) 
Bile duct stone * 1  2/2291 (0.09%)  1/2313 (0.04%) 
Biliary colic * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Cholecystitis chronic * 1  1/2291 (0.04%)  2/2313 (0.09%) 
Hepatitis toxic * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Jaundice * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Hepatic cirrhosis * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Cholestasis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Cytolytic hepatitis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Immune system disorders     
Hypersensitivity * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Sarcoidosis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Infections and infestations     
Pneumonia * 1  32/2291 (1.40%)  45/2313 (1.95%) 
Urinary tract infection * 1  6/2291 (0.26%)  10/2313 (0.43%) 
Cellulitis * 1  5/2291 (0.22%)  7/2313 (0.30%) 
Gastroenteritis * 1  5/2291 (0.22%)  6/2313 (0.26%) 
Lobar pneumonia * 1  5/2291 (0.22%)  6/2313 (0.26%) 
Diverticulitis * 1  4/2291 (0.17%)  4/2313 (0.17%) 
Bronchitis * 1  4/2291 (0.17%)  3/2313 (0.13%) 
Appendicitis * 1  4/2291 (0.17%)  2/2313 (0.09%) 
Bronchopneumonia * 1  4/2291 (0.17%)  2/2313 (0.09%) 
Sepsis * 1  3/2291 (0.13%)  3/2313 (0.13%) 
Urosepsis * 1  2/2291 (0.09%)  4/2313 (0.17%) 
Pyelonephritis chronic * 1  2/2291 (0.09%)  2/2313 (0.09%) 
Herpes zoster * 1  2/2291 (0.09%)  1/2313 (0.04%) 
Pyelonephritis * 1  2/2291 (0.09%)  1/2313 (0.04%) 
Bronchiectasis * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Mastitis * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Respiratory tract infection viral * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Septic shock * 1  1/2291 (0.04%)  4/2313 (0.17%) 
Upper respiratory tract infection * 1  1/2291 (0.04%)  3/2313 (0.13%) 
Viral infection * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Abscess * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Abscess limb * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Abscess oral * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Acarodermatitis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Clonorchiasis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Diarrhoea infectious * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Encephalitis viral * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Epstein-barr virus infection * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Escherichia sepsis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Gastroenteritis viral * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Hepatitis a * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Infected epidermal cyst * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Infection * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Influenza * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Localised infection * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Opisthorchiasis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Orchitis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Osteomyelitis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Osteomyelitis chronic * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Pancreatitis viral * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Peritoneal infection * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Pneumonia bacterial * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Pneumonia klebsiella * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Rectal abscess * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Respiratory tract infection * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Skin infection * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Soft tissue infection * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Wound infection bacterial * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Erysipelas * 1  0/2291 (0.00%)  4/2313 (0.17%) 
Device related infection * 1  0/2291 (0.00%)  3/2313 (0.13%) 
Sinusitis * 1  0/2291 (0.00%)  3/2313 (0.13%) 
Clostridium difficile colitis * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Obstructive chronic bronchitis with acute exacerbation * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Postoperative wound infection * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Pyelonephritis acute * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Abdominal abscess * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Bacteraemia * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Bursitis infective * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Diabetic gangrene * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Gastroenteritis salmonella * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Groin infection * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Hiv infection * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Infective exacerbation of chronic obstructive airways disease * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Labyrinthitis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Lower respiratory tract infection * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Paronychia * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Peridiverticular abscess * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Peritonsillar abscess * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Pneumonia legionella * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Pneumonia pneumococcal * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Pneumonia staphylococcal * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Post procedural infection * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Pyothorax * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Staphylococcal infection * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Staphylococcal sepsis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Tinea cruris * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Tracheobronchitis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Injury, poisoning and procedural complications     
Fall * 1  20/2291 (0.87%)  20/2313 (0.86%) 
Hip fracture * 1  5/2291 (0.22%)  2/2313 (0.09%) 
Road traffic accident * 1  3/2291 (0.13%)  3/2313 (0.13%) 
Contusion * 1  3/2291 (0.13%)  2/2313 (0.09%) 
Femoral neck fracture * 1  3/2291 (0.13%)  0/2313 (0.00%) 
Therapeutic agent toxicity * 1  3/2291 (0.13%)  0/2313 (0.00%) 
Tendon rupture * 1  2/2291 (0.09%)  2/2313 (0.09%) 
Accidental overdose * 1  2/2291 (0.09%)  1/2313 (0.04%) 
Femur fracture * 1  2/2291 (0.09%)  1/2313 (0.04%) 
Rib fracture * 1  2/2291 (0.09%)  1/2313 (0.04%) 
Alcohol poisoning * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Lower limb fracture * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Spinal compression fracture * 1  1/2291 (0.04%)  4/2313 (0.17%) 
Humerus fracture * 1  1/2291 (0.04%)  3/2313 (0.13%) 
Traumatic haematoma * 1  1/2291 (0.04%)  3/2313 (0.13%) 
Brain contusion * 1  1/2291 (0.04%)  2/2313 (0.09%) 
Lumbar vertebral fracture * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Post procedural haematoma * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Post-traumatic pain * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Pubic rami fracture * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Skull fracture * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Subdural haematoma * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Traumatic arthritis * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Acetabulum fracture * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Anaemia postoperative * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Anastomotic complication * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Asbestosis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Cervical vertebral fracture * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Device failure * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Foot fracture * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Head injury * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Incisional hernia * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Joint injury * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Medical device pain * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Patella fracture * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Post procedural haemorrhage * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Postoperative heterotopic calcification * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Transfusion reaction * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Dislocation of joint prosthesis * 1  0/2291 (0.00%)  5/2313 (0.22%) 
Ankle fracture * 1  0/2291 (0.00%)  3/2313 (0.13%) 
Arterial injury * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Concussion * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Device migration * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Facial bones fracture * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Fibula fracture * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Graft thrombosis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Hand fracture * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Injury * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Joint dislocation * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Muscle injury * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Operative haemorrhage * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Overdose * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Pelvic fracture * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Penetrating abdominal trauma * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Procedural pain * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Spinal cord injury cervical * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Traumatic arthropathy * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Investigations     
Blood creatinine increased * 1  5/2291 (0.22%)  1/2313 (0.04%) 
International normalised ratio increased * 1  4/2291 (0.17%)  6/2313 (0.26%) 
Electrocardiogram qt prolonged * 1  4/2291 (0.17%)  1/2313 (0.04%) 
Weight decreased * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Cardioactive drug level increased * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Coagulation test abnormal * 1  1/2291 (0.04%)  0/2313 (0.00%) 
International normalised ratio decreased * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Prothrombin time prolonged * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Alanine aminotransferase increased * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Aspartate aminotransferase increased * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Blood creatine phosphokinase increased * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Glycosylated haemoglobin increased * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Hepatitis c positive * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Transaminases increased * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Metabolism and nutrition disorders     
Dehydration * 1  4/2291 (0.17%)  10/2313 (0.43%) 
Diabetes mellitus * 1  4/2291 (0.17%)  3/2313 (0.13%) 
Hypoglycaemia * 1  3/2291 (0.13%)  3/2313 (0.13%) 
Hyponatraemia * 1  3/2291 (0.13%)  2/2313 (0.09%) 
Hypokalaemia * 1  2/2291 (0.09%)  3/2313 (0.13%) 
Gout * 1  1/2291 (0.04%)  2/2313 (0.09%) 
Anorexia * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Hyperglycaemia * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Hyperkalaemia * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Fluid overload * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Metabolic acidosis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Vitamin b12 deficiency * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Failure to thrive * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Type 2 diabetes mellitus * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Musculoskeletal and connective tissue disorders     
Osteoarthritis * 1  15/2291 (0.65%)  21/2313 (0.91%) 
Arthralgia * 1  4/2291 (0.17%)  2/2313 (0.09%) 
Musculoskeletal chest pain * 1  2/2291 (0.09%)  2/2313 (0.09%) 
Intervertebral disc protrusion * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Back pain * 1  1/2291 (0.04%)  5/2313 (0.22%) 
Muscular weakness * 1  1/2291 (0.04%)  4/2313 (0.17%) 
Rotator cuff syndrome * 1  1/2291 (0.04%)  4/2313 (0.17%) 
Pain in extremity * 1  1/2291 (0.04%)  3/2313 (0.13%) 
Lumbar spinal stenosis * 1  1/2291 (0.04%)  2/2313 (0.09%) 
Rheumatoid arthritis * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Arthropathy * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Bursitis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Dupuytren's contracture * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Gouty arthritis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Joint swelling * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Muscle spasms * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Spondylolisthesis acquired * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Sympathetic posterior cervical syndrome * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Haemarthrosis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Intervertebral disc compression * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Neck mass * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Osteonecrosis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Osteoporotic fracture * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Pathological fracture * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Polyarthritis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Polymyalgia rheumatica * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Rhabdomyolysis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Spondylolysis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Prostate cancer * 1  6/2291 (0.26%)  11/2313 (0.48%) 
Colon cancer * 1  5/2291 (0.22%)  5/2313 (0.22%) 
Breast cancer * 1  3/2291 (0.13%)  5/2313 (0.22%) 
Basal cell carcinoma * 1  2/2291 (0.09%)  3/2313 (0.13%) 
Lung neoplasm malignant * 1  2/2291 (0.09%)  2/2313 (0.09%) 
B-cell lymphoma * 1  2/2291 (0.09%)  1/2313 (0.04%) 
Oesophageal adenocarcinoma * 1  2/2291 (0.09%)  1/2313 (0.04%) 
Pancreatic carcinoma * 1  2/2291 (0.09%)  1/2313 (0.04%) 
Renal cell carcinoma stage unspecified * 1  2/2291 (0.09%)  1/2313 (0.04%) 
Squamous cell carcinoma * 1  2/2291 (0.09%)  1/2313 (0.04%) 
Bladder neoplasm * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Uterine cancer * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Bladder cancer * 1  1/2291 (0.04%)  3/2313 (0.13%) 
Lung adenocarcinoma * 1  1/2291 (0.04%)  2/2313 (0.09%) 
Lung squamous cell carcinoma stage unspecified * 1  1/2291 (0.04%)  2/2313 (0.09%) 
Malignant melanoma * 1  1/2291 (0.04%)  2/2313 (0.09%) 
Non-small cell lung cancer * 1  1/2291 (0.04%)  2/2313 (0.09%) 
Prostatic adenoma * 1  1/2291 (0.04%)  2/2313 (0.09%) 
Hepatic neoplasm malignant * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Lung adenocarcinoma metastatic * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Non-small cell lung cancer metastatic * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Rectal cancer * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Acute myeloid leukaemia * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Benign neoplasm of thyroid gland * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Bladder papilloma * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Bladder transitional cell carcinoma * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Brain neoplasm * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Bronchioloalveolar carcinoma * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Carcinoid tumour pulmonary * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Colon adenoma * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Endometrial cancer * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Hepatic neoplasm * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Leiomyosarcoma metastatic * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Lung cancer metastatic * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Metastases to lung * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Metastasis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Metastatic carcinoma of the bladder * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Multiple myeloma * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Myeloproliferative disorder * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Nasal cavity cancer * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Oesophageal cancer metastatic * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Pancreatic neoplasm * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Rectal neoplasm * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Squamous cell carcinoma of skin * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Thymoma malignant * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Urethral adenoma * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Ovarian adenoma * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Prostate cancer metastatic * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Adrenal adenoma * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Benign peritoneal neoplasm * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Breast cancer recurrent * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Breast cancer stage iii * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Bronchial carcinoma * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Colorectal cancer * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Gastric cancer * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Glioblastoma * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Inflammatory carcinoma of the breast * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Large intestine carcinoma * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Lip and/or oral cavity cancer * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Lung neoplasm * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Lymphoma * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Malignant pleural effusion * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Metastases to liver * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Myelodysplastic syndrome * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Ocular neoplasm * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Ovarian cancer * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Papillary serous endometrial carcinoma * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Pituitary tumour benign * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Plasmacytoma * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Pleura carcinoma * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Renal neoplasm * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Small cell lung cancer metastatic * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Small cell lung cancer stage unspecified * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Tumour ulceration * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Vulval cancer * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Nervous system disorders     
Dizziness * 1  3/2291 (0.13%)  2/2313 (0.09%) 
Transient ischaemic attack * 1  2/2291 (0.09%)  2/2313 (0.09%) 
Dementia alzheimer's type * 1  2/2291 (0.09%)  1/2313 (0.04%) 
Ischaemic stroke * 1  2/2291 (0.09%)  1/2313 (0.04%) 
Sciatica * 1  2/2291 (0.09%)  1/2313 (0.04%) 
Syncope * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Brain mass * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Cerebrovascular disorder * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Headache * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Intracranial aneurysm * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Lumbar radiculopathy * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Pseudobulbar palsy * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Spinal claudication * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Vascular encephalopathy * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Vertebrobasilar insufficiency * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Carpal tunnel syndrome * 1  0/2291 (0.00%)  3/2313 (0.13%) 
Cerebrovascular accident * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Partial seizures * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Amyotrophic lateral sclerosis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Convulsion * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Diplegia * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Epilepsy * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Facial palsy * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Guillain-barre syndrome * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Haemorrhagic stroke * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Hepatic encephalopathy * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Loss of consciousness * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Metabolic encephalopathy * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Mononeuritis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Toxic encephalopathy * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Psychiatric disorders     
Depression * 1  3/2291 (0.13%)  1/2313 (0.04%) 
Mental status changes * 1  1/2291 (0.04%)  3/2313 (0.13%) 
Generalised anxiety disorder * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Major depression * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Anxiety * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Alcohol withdrawal syndrome * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Alcoholism * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Confusional state * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Delirium tremens * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Post-traumatic stress disorder * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Suicide attempt * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Renal and urinary disorders     
Renal failure acute * 1  14/2291 (0.61%)  4/2313 (0.17%) 
Haematuria * 1  7/2291 (0.31%)  7/2313 (0.30%) 
Calculus urinary * 1  2/2291 (0.09%)  2/2313 (0.09%) 
Nephrolithiasis * 1  2/2291 (0.09%)  2/2313 (0.09%) 
Diabetic nephropathy * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Hydronephrosis * 1  1/2291 (0.04%)  2/2313 (0.09%) 
Urinary retention * 1  1/2291 (0.04%)  2/2313 (0.09%) 
Renal colic * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Renal failure * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Renal failure chronic * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Calculus bladder * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Nocturia * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Renal impairment * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Urinary bladder polyp * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Bladder obstruction * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Cystitis haemorrhagic * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Cystitis noninfective * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Stress urinary incontinence * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Urethral stenosis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia * 1  8/2291 (0.35%)  10/2313 (0.43%) 
Uterine polyp * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Acquired hydrocele * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Breast discomfort * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Endometrial hyperplasia * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Penis disorder * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Uterine prolapse * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Prostatitis * 1  0/2291 (0.00%)  3/2313 (0.13%) 
Vaginal prolapse * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Adnexa uteri cyst * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Epididymitis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Gynaecomastia * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease * 1  13/2291 (0.57%)  19/2313 (0.82%) 
Asthma * 1  5/2291 (0.22%)  2/2313 (0.09%) 
Respiratory failure * 1  4/2291 (0.17%)  1/2313 (0.04%) 
Pleural effusion * 1  3/2291 (0.13%)  4/2313 (0.17%) 
Pleurisy * 1  3/2291 (0.13%)  0/2313 (0.00%) 
Haemoptysis * 1  2/2291 (0.09%)  3/2313 (0.13%) 
Interstitial lung disease * 1  2/2291 (0.09%)  1/2313 (0.04%) 
Epistaxis * 1  1/2291 (0.04%)  4/2313 (0.17%) 
Dyspnoea * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Hypoxia * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Pulmonary fibrosis * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Acute respiratory failure * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Emphysema * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Lung disorder * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Nasal turbinate hypertrophy * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Obstructive airways disorder * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Pneumonitis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Sleep apnoea syndrome * 1  0/2291 (0.00%)  3/2313 (0.13%) 
Pneumonia aspiration * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Bronchopneumopathy * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Cough * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Nasal polyps * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Pulmonary mass * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Pulmonary oedema * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Skin and subcutaneous tissue disorders     
Skin ulcer * 1  2/2291 (0.09%)  0/2313 (0.00%) 
Panniculitis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Pemphigoid * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Photodermatosis * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Pruritus * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Urticaria * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Rash * 1  0/2291 (0.00%)  2/2313 (0.09%) 
Decubitus ulcer * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Dermatitis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Dermatitis bullous * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Psoriasis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Social circumstances     
Victim of crime * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Surgical and medical procedures     
Ileostomy closure * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Shoulder arthroplasty * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Suprapubic catheter insertion * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Transurethral prostatectomy * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Hip arthroplasty * 1  0/2291 (0.00%)  3/2313 (0.13%) 
Knee operation * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Pilonidal sinus repair * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Vascular disorders     
Haematoma * 1  3/2291 (0.13%)  3/2313 (0.13%) 
Aortic aneurysm * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Femoral arterial stenosis * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Haemorrhage * 1  1/2291 (0.04%)  1/2313 (0.04%) 
Hypovolaemic shock * 1  1/2291 (0.04%)  0/2313 (0.00%) 
Angiodysplasia * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Iliac artery embolism * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Lymphoedema * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Peripheral embolism * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Thrombophlebitis * 1  0/2291 (0.00%)  1/2313 (0.04%) 
Varicose vein * 1  0/2291 (0.00%)  1/2313 (0.04%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (10.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Dronedarone 400mg Bid Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   1584/2291 (69.14%)   1527/2313 (66.02%) 
Cardiac disorders     
Any cardiac disorders * 1  251/2291 (10.96%)  213/2313 (9.21%) 
Gastrointestinal disorders     
Any Gastrointestinal disorders * 1  573/2291 (25.01%)  478/2313 (20.67%) 
Diarrhoea * 1  222/2291 (9.69%)  142/2313 (6.14%) 
Nausea * 1  122/2291 (5.33%)  71/2313 (3.07%) 
General disorders     
Any general disorders and administration site conditions * 1  397/2291 (17.33%)  348/2313 (15.05%) 
Oedema peripheral * 1  147/2291 (6.42%)  119/2313 (5.14%) 
Fatigue * 1  115/2291 (5.02%)  90/2313 (3.89%) 
Infections and infestations     
Any infections and infestations * 1  508/2291 (22.17%)  533/2313 (23.04%) 
Injury, poisoning and procedural complications     
Any injury, poisoning and procedural complications * 1  187/2291 (8.16%)  198/2313 (8.56%) 
Investigations     
Any investigation disorders * 1  298/2291 (13.01%)  199/2313 (8.60%) 
Metabolism and nutrition disorders     
Any metabolism and nutrition disorders * 1  171/2291 (7.46%)  183/2313 (7.91%) 
Musculoskeletal and connective tissue disorders     
Any musculoskeletal and connective tissue disorders * 1  364/2291 (15.89%)  376/2313 (16.26%) 
Nervous system disorders     
Any nervous system disorders * 1  362/2291 (15.80%)  365/2313 (15.78%) 
Dizziness * 1  160/2291 (6.98%)  145/2313 (6.27%) 
Psychiatric disorders     
Any psychiatric disorders * 1  106/2291 (4.63%)  125/2313 (5.40%) 
Respiratory, thoracic and mediastinal disorders     
Any respiratory, thoracic and mediastinal disorders * 1  315/2291 (13.75%)  318/2313 (13.75%) 
Dyspnoea * 1  120/2291 (5.24%)  96/2313 (4.15%) 
Skin and subcutaneous tissue disorders     
Any skin and subcutaneous tissue disorders * 1  235/2291 (10.26%)  174/2313 (7.52%) 
Vascular disorders     
Any vascular disorders * 1  179/2291 (7.81%)  187/2313 (8.08%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (10.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such publication for comment at least 45 days before any submission for publication. If requested by the Sponsor, any submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
Name/Title: International Clinical Development (ICD), Clinical Study Director
Organization: sanofi-aventis
Responsible Party: International Clinical Development - Study Director, sanofi-aventis
ClinicalTrials.gov Identifier: NCT00174785     History of Changes
Other Study ID Numbers: EFC5555
First Submitted: September 13, 2005
First Posted: September 15, 2005
Results First Submitted: July 24, 2009
Results First Posted: December 23, 2009
Last Update Posted: January 12, 2010