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Trial record 2 of 16 for:    PALLAS

Permanent Atrial fibriLLAtion Outcome Study Using Dronedarone on Top of Standard Therapy (PALLAS)

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ClinicalTrials.gov Identifier: NCT01151137
Recruitment Status : Terminated (The study was stopped because of safety concerns)
First Posted : June 25, 2010
Results First Posted : October 26, 2012
Last Update Posted : October 26, 2012
Sponsor:
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Atrial Fibrillation
Interventions Drug: Dronedarone
Drug: Placebo (for Dronedarone)
Enrollment 3236
Recruitment Details

Recruitment initiated in July 2010 was discontinued on July 6, 2011 upon recommendations of the Data Monitoring Committee due to an increased number of observed cardiovascular events in the Dronedarone group. The common study end date [CSED] was defined as July 15, 2011.

At that time 494 sites in 37 countries had enrolled at least one patient.

Pre-assignment Details

Assignment to groups was done centrally using an Interactive Voice Response System [IVRS] or an Interactive Web Response System [IWRS] in a 1:1 ratio.

A total of 3236 participants were randomized at 489 sites (instead of 10800 as initially planned). The median duration of their participation in the study was 3.5 months.

Arm/Group Title Placebo Dronedarone
Hide Arm/Group Description Placebo twice daily until the CSED (median treatment duration of 87.5 days) Dronedarone 400 mg twice daily until the CSED (median treatment duration of 74 days)
Period Title: Overall Study
Started 1617 1619
Treated 1610 [1] 1613
Discontinued Treatment 171 342
Completed 1601 1591
Not Completed 16 28
Reason Not Completed
Death             15             27
Lost to Follow-up             1             1
[1]
One participant randomized to the placebo group received Dronedarone for 7 days by mistake
Arm/Group Title Placebo Dronedarone Total
Hide Arm/Group Description Placebo twice daily until the CSED (median treatment duration of 87.5 days) Dronedarone 400 mg twice daily until the CSED (median treatment duration of 74 days) Total of all reporting groups
Overall Number of Baseline Participants 1617 1619 3236
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1617 participants 1619 participants 3236 participants
75.0  (5.9) 75.0  (5.9) 75.0  (5.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1617 participants 1619 participants 3236 participants
Female
577
  35.7%
568
  35.1%
1145
  35.4%
Male
1040
  64.3%
1051
  64.9%
2091
  64.6%
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1617 participants 1619 participants 3236 participants
North America 281 266 547
South America 227 236 463
Western Europe 459 475 934
Eastern Europe 495 488 983
Asia 53 47 100
Rest of the word 102 107 209
[1]
Measure Description:

Regions were defined as follows:

  • North America: Canada, United States
  • South America: Argentina, Brazil, Chile, Mexico
  • Western Europe: Austria, Belgium, Denmark, Finland, France, Germany, Greece, Italy, Netherlands, Norway, Spain, Sweden, Switzerland, United Kingdom
  • Eastern Europe: Bulgaria, Czech Republic, Hungary, Poland, Romania, Russian Federation, Slovakia, Ukraine Asia: Hong Kong, Republic of Korea, Malaysia, Singapore, Taiwan Rest of the World: Australia, Israel, New zealand, South Africa
Permanent atrial fibrillation [AF] history  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1617 participants 1619 participants 3236 participants
6 months to 2 years 490 498 988
> 2 years 1124 1119 2243
Unknown 3 2 5
CHADS2 Score   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1617 participants 1619 participants 3236 participants
< 2 172 191 363
≥ 2 1444 1427 2871
Unavailable 1 1 2
[1]
Measure Description:

CHADS2 is a risk-prediction score ranging from 0 to 6 used estimate Stroke Risk in Atrial Fibrillation patients.

CHADS2 score is obtained by adding together the points that correspond to the conditions that are present:

  • C: Congestive Heart Failure history: 1 point
  • H: Hypertension history: 1 point
  • A: Age ≥75 years: 1 point
  • D: Diabetes Mellitus history: 1 point
  • S: Stroke symptoms previously or Transient Ischemic Attack [TIA]: 2 points
New York Heart Association [NYHA] class   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1617 participants 1619 participants 3236 participants
No congestive heart failure [CHF] 535 512 1047
NYHA Class I 209 234 443
NYHA Class II 749 732 1481
NYHA Class III 124 141 265
[1]
Measure Description:

NYHA classification is a functional classification that places the patient in one of 4 categories, based on how much he/she is limited during physical activity:

  • Class I: no limitation of activities; the patient suffers no symptoms from ordinary activities.
  • Class II: slight, mild limitation of activity; the patient is comfortable with rest or with mild exertion.
  • Class III: marked limitation of activity; the patient is comfortable only at rest.
  • Class IV: complete rest, confined to bed or chair; any physical activity brings on discomfort and symptoms occur at rest.
1.Primary Outcome
Title Overview of the Two Co-primary Outcomes
Hide Description

First co-primary outcome was defined as the first event among stroke, systemic arterial embolism, Myocardial Infarctions [MI], or cardiovascular death.

Second co-primary outcome was defined as the first event among unscheduled cardiovascular hospitalization or death from any cause.

Both co-primary outcomes were determined based on the central review and adjudication by a blinded Adjudication Committee of all reported deaths (from any cause), MI, systemic arterial embolisms, strokes, Transient Ischemic Attacks [TIA], Heart Failure hospitalization and unplanned hospitalisations for cardiovascular cause.

Time Frame From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants considered in the treatment group to which they were randomized regardless of the treatment they actually received
Arm/Group Title Placebo Dronedarone
Hide Arm/Group Description:
Placebo twice daily until the CSED (median treatment duration of 87.5 days)
Dronedarone 400 mg twice daily until the CSED (median treatment duration of 74 days)
Overall Number of Participants Analyzed 1617 1619
Measure Type: Number
Unit of Measure: participants
First co-primary endpoint 19 43
Second co-primary endpoint 67 127
2.Primary Outcome
Title Time to First Co-primary Outcome (Cumulative Incidence Function)
Hide Description

Time to first co-primary outcome was defined as the time from randomization to the first event among stroke, systemic arterial embolism, MI or cardiovascular death.

Cumulative incidence function in each treatment group was calculated using non-parametric Kaplan-Meier estimate.

95% confidence interval was computed at each time-point using Greenwood’s variance estimation.

Time Frame From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population as previously defined
Arm/Group Title Placebo Dronedarone
Hide Arm/Group Description:
Placebo twice daily until the CSED (median treatment duration of 87.5 days)
Dronedarone 400 mg twice daily until the CSED (median treatment duration of 74 days)
Overall Number of Participants Analyzed 1617 1619
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
Cumulative incidence at 14 days
0.002
(0.000 to 0.004)
0.009
(0.005 to 0.014)
Cumulative incidence at 30 days
0.003
(0.000 to 0.006)
0.013
(0.008 to 0.019)
Cumulative incidence at 90 days
0.007
(0.003 to 0.012)
0.021
(0.014 to 0.029)
Cumulative incidence at 180 days
0.013
(0.006 to 0.021)
0.042
(0.028 to 0.056)
Cumulative incidence at 270 days
0.038
(0.012 to 0.064)
0.045
(0.030 to 0.061)
Cumulative incidence at 360 days
0.038
(0.012 to 0.064)
0.045
(0.030 to 0.061)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dronedarone
Comments As a consequence of the early termination of the study, the analysis was performed for information only without any adjustment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments A priori threshold for statistical significance: 0.05
Method Log Rank
Comments 2-sided Log-rank’s asymptotic test
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.294
Confidence Interval (2-Sided) 95%
1.337 to 3.936
Estimation Comments

Hazard ratio (HR) of Dronedarone versus placebo for stroke, systemic arterial embolism, myocardial infarction or cardiovascular death

HR and confidence interval were estimated using Cox regression model with treatment group as the only factor.

3.Primary Outcome
Title Time to Second Co-primary Outcome (Cumulative Incidence Function)
Hide Description

Time to second co-primary outcome was defined as the time from randomization to the first event among unscheduled cardiovascular hospitalization or death from any cause.

Cumulative incidence function in each treatment group was calculated using non-parametric Kaplan-Meier estimate.

95% confidence interval was computed at each time-point using Greenwood’s variance estimation.

Time Frame From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population as previously defined
Arm/Group Title Placebo Dronedarone
Hide Arm/Group Description:
Placebo twice daily until the CSED (median treatment duration of 87.5 days)
Dronedarone 400 mg twice daily until the CSED (median treatment duration of 74 days)
Overall Number of Participants Analyzed 1617 1619
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
Cumulative incidence at 14 days
0.005
(0.002 to 0.008)
0.020
(0.013 to 0.027)
Cumulative incidence at 30 days
0.014
(0.008 to 0.020)
0.034
(0.025 to 0.043)
Cumulative incidence at 90 days
0.033
(0.023 to 0.042)
0.069
(0.055 to 0.083)
Cumulative incidence at 180 days
0.059
(0.043 to 0.075)
0.110
(0.089 to 0.130)
Cumulative incidence at 270 days
0.099
(0.062 to 0.137)
0.137
(0.107 to 0.167)
Cumulative incidence at 360 days
0.099
(0.062 to 0.137)
0.137
(0.107 to 0.167)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dronedarone
Comments As a consequence of the early termination of the study, the analysis was performed for information only without any adjustment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments A priori threshold for statistical significance: 0.05
Method Log Rank
Comments 2-sided Log-rank's asymptotic test
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.947
Confidence Interval (2-Sided) 95%
1.448 to 2.617
Estimation Comments

Hazard ratio (HR) of Dronedarone versus placebo for unscheduled cardiovascular hospitalization or death from any cause

HR and confidence interval were estimated using Cox regression model with treatment group as the only factor.

4.Secondary Outcome
Title Deaths
Hide Description Deaths were classified according to the primary cause of death.
Time Frame From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population as previously defined
Arm/Group Title Placebo Dronedarone
Hide Arm/Group Description:
Placebo twice daily until the CSED (median treatment duration of 87.5 days)
Dronedarone 400 mg twice daily until the CSED (median treatment duration of 74 days)
Overall Number of Participants Analyzed 1617 1619
Measure Type: Number
Unit of Measure: participants
Any death 13 25
- Cardiovascular death 10 21
--- Cardiac arrhythmic death 4 13
5.Secondary Outcome
Title Time to Cardiovascular Death (Cumulative Incidence Function)
Hide Description

Time to cardiovascular death was defined as the time from randomization to the death.

Cumulative incidence function in each treatment group was calculated using non-parametric Kaplan-Meier estimate.

95% confidence interval was computed at each time-point using Greenwood's variance estimation.

Time Frame From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population as previously defined
Arm/Group Title Placebo Dronedarone
Hide Arm/Group Description:
Placebo twice daily until the CSED (median treatment duration of 87.5 days)
Dronedarone 400 mg twice daily until the CSED (median treatment duration of 74 days)
Overall Number of Participants Analyzed 1617 1619
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
Cumulative incidence at 14 days
0.001
(0.000 to 0.003)
0.003
(0.000 to 0.006)
Cumulative incidence at 30 days
0.003
(0.000 to 0.006)
0.005
(0.002 to 0.009)
Cumulative incidence at 90 days
0.004
(0.001 to 0.007)
0.008
(0.003 to 0.012)
Cumulative incidence at 180 days
0.004
(0.001 to 0.007)
0.022
(0.012 to 0.033)
Cumulative incidence at 270 days
0.027
(0.001 to 0.052)
0.026
(0.013 to 0.038)
Cumulative incidence at 360 days
0.027
(0.001 to 0.052)
0.026
(0.013 to 0.038)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Dronedarone
Comments As a consequence of the early termination of the study, the analysis was performed for information only without any adjustment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0460
Comments A priori threshold for statistical significance: 0.05
Method Log Rank
Comments 2-sided Log-rank's asymptotic test
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.115
Confidence Interval (2-Sided) 95%
0.996 to 4.490
Estimation Comments

Hazard ratio (HR) of Dronedarone versus placebo for cardiovascular death

HR and confidence interval were estimated using Cox regression model with treatment group as the only factor.

6.Other Pre-specified Outcome
Title Overview of Cardiovascular Events
Hide Description [Not Specified]
Time Frame From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population as previously defined
Arm/Group Title Placebo Dronedarone
Hide Arm/Group Description:
Placebo twice daily until the CSED (median treatment duration of 87.5 days)
Dronedarone 400 mg twice daily until the CSED (median treatment duration of 74 days)
Overall Number of Participants Analyzed 1617 1619
Measure Type: Number
Unit of Measure: participants
MI or unstable angina pectoris 8 15
- MI 2 3
Stroke 10 23
- Ischemic stroke 9 18
Systemic arterial embolism 0 1
Episode of heart failure 55 115
- Hospitalization due to heart failure 24 43
Unplanned hospitalization for cardiovascular cause 59 113
7.Other Pre-specified Outcome
Title Overview of Adverse Events [AE]
Hide Description AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.
Time Frame from first study drug intake up to 10 days after the last study drug intake
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population: all randomized and treated participants. Participants were considered according to the treatment actually received. Consequently the participant randomized to the placebo group who received Dronedarone was included in the Dronedarone group.
Arm/Group Title Placebo Dronedarone
Hide Arm/Group Description:
Placebo twice daily until the CSED (median treatment duration of 87.5 days)
Dronedarone 400 mg twice daily until the CSED (median treatment duration of 74 days)
Overall Number of Participants Analyzed 1609 1614
Measure Type: Number
Unit of Measure: participants
Any AE 600 797
- Any serious AE 77 113
- Any AE leading to death 0 4
- Any AE leading to treatment discontinuation 80 212
- Any AE leading to hospitalization 71 95
Time Frame All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent Form up to the last visit.
Adverse Event Reporting Description

The analysis included all randomized participants who received at least one dose of study drug and all AE that developed or worsened from randomization up to 10 days after last study drug intake.

Participants were considered according to the treatment actually received regardless the amount of treatment administered.

 
Arm/Group Title Placebo Dronedarone
Hide Arm/Group Description Placebo twice daily until the CSED (median treatment duration of 87.5 days) Dronedarone 400 mg twice daily until the CSED (median treatment duration of 74 days)
All-Cause Mortality
Placebo Dronedarone
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Dronedarone
Affected / at Risk (%) Affected / at Risk (%)
Total   77/1609 (4.79%)   113/1614 (7.00%) 
Blood and lymphatic system disorders     
Anaemia * 1  1/1609 (0.06%)  2/1614 (0.12%) 
Iron deficiency anaemia * 1  1/1609 (0.06%)  2/1614 (0.12%) 
Coagulopathy * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Cardiac disorders     
Bradycardia * 1  1/1609 (0.06%)  1/1614 (0.06%) 
Tachycardia * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Ear and labyrinth disorders     
Vertigo * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Eye disorders     
Cataract * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Optic ischaemic neuropathy * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Gastrointestinal disorders     
Diarrhoea * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Nausea * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Abdominal pain * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Dyspepsia * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Vomiting * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Constipation * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Gastrointestinal haemorrhage * 1  0/1609 (0.00%)  3/1614 (0.19%) 
Colitis * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Enteritis * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Subileus * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Gastrointestinal ulcer haemorrhage * 1  0/1609 (0.00%)  2/1614 (0.12%) 
Gastric haemorrhage * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Gastric perforation * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Gastric ulcer haemorrhage * 1  1/1609 (0.06%)  1/1614 (0.06%) 
Gastrointestinal necrosis * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Ileitis * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Inguinal hernia * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Large intestine perforation * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Pancreatitis * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Rectal haemorrhage * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Abdominal wall haematoma * 1  1/1609 (0.06%)  0/1614 (0.00%) 
General disorders     
Oedema peripheral * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Chest pain * 1  0/1609 (0.00%)  2/1614 (0.12%) 
Non-cardiac chest pain * 1  1/1609 (0.06%)  1/1614 (0.06%) 
Generalised oedema * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Hepatobiliary disorders     
Cholecystitis * 1  0/1609 (0.00%)  2/1614 (0.12%) 
Cholelithiasis * 1  2/1609 (0.12%)  2/1614 (0.12%) 
Acute hepatic failure * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Cholangitis * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Cholecystitis acute * 1  1/1609 (0.06%)  1/1614 (0.06%) 
Hepatic congestion * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Hepatitis * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Bile duct obstruction * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Bile duct stone * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Infections and infestations     
Bronchitis * 1  1/1609 (0.06%)  2/1614 (0.12%) 
Urinary tract infection * 1  2/1609 (0.12%)  2/1614 (0.12%) 
Pneumonia * 1  9/1609 (0.56%)  10/1614 (0.62%) 
Gastroenteritis * 1  0/1609 (0.00%)  3/1614 (0.19%) 
Cellulitis * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Respiratory tract infection * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Cystitis * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Erysipelas * 1  2/1609 (0.12%)  0/1614 (0.00%) 
Pneumonia bacterial * 1  0/1609 (0.00%)  2/1614 (0.12%) 
Appendicitis * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Bronchopneumonia * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Escherichia sepsis * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Lobar pneumonia * 1  1/1609 (0.06%)  1/1614 (0.06%) 
Otitis media chronic * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Postoperative wound infection * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Sepsis * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Urosepsis * 1  1/1609 (0.06%)  1/1614 (0.06%) 
Arthritis bacterial * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Intervertebral discitis * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Clostridial infection * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Fungal peritonitis * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Clostridium difficile colitis * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Diverticulitis * 1  2/1609 (0.12%)  0/1614 (0.00%) 
Gangrene * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Pyelonephritis * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Injury, poisoning and procedural complications     
Fall * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Contusion * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Rib fracture * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Toxicity to various agents * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Head injury * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Hip fracture * 1  1/1609 (0.06%)  1/1614 (0.06%) 
Multiple fractures * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Cervical vertebral fracture * 1  1/1609 (0.06%)  1/1614 (0.06%) 
Post procedural complication * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Upper limb fracture * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Fractured sacrum * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Hand fracture * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Joint dislocation * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Road traffic accident * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Lumbar vertebral fracture * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Investigations     
Blood creatinine increased * 1  0/1609 (0.00%)  2/1614 (0.12%) 
Alanine aminotransferase increased * 1  0/1609 (0.00%)  1/1614 (0.06%) 
International normalised ratio increased * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Hepatic enzyme increased * 1  1/1609 (0.06%)  5/1614 (0.31%) 
Metabolism and nutrition disorders     
Gout * 1  2/1609 (0.12%)  1/1614 (0.06%) 
Dehydration * 1  2/1609 (0.12%)  2/1614 (0.12%) 
Hypoglycaemia * 1  1/1609 (0.06%)  2/1614 (0.12%) 
Hyponatraemia * 1  3/1609 (0.19%)  0/1614 (0.00%) 
Electrolyte depletion * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Electrolyte imbalance * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Metabolic acidosis * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Hyperglycaemia * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Diabetic foot * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  2/1609 (0.12%)  0/1614 (0.00%) 
Osteoarthritis * 1  2/1609 (0.12%)  3/1614 (0.19%) 
Musculoskeletal chest pain * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Rhabdomyolysis * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Spinal column stenosis * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Prostate cancer recurrent * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Renal cancer * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Uterine leiomyoma * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Prostate cancer * 1  0/1609 (0.00%)  1/1614 (0.06%) 
B-cell lymphoma * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Bladder cancer * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Hepatic neoplasm malignant * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Myeloproliferative disorder * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Skin cancer * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Squamous cell carcinoma * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Nervous system disorders     
Dizziness * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Syncope * 1  2/1609 (0.12%)  1/1614 (0.06%) 
Presyncope * 1  0/1609 (0.00%)  2/1614 (0.12%) 
Diabetic neuropathy * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Encephalitis * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Epilepsy * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Peripheral sensory neuropathy * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Cognitive disorder * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Dementia * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Psychiatric disorders     
Mental status changes * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Delirium * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Renal and urinary disorders     
Renal failure * 1  2/1609 (0.12%)  3/1614 (0.19%) 
Renal failure acute * 1  1/1609 (0.06%)  8/1614 (0.50%) 
Haematuria * 1  1/1609 (0.06%)  2/1614 (0.12%) 
Renal failure chronic * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Nephrolithiasis * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Proteinuria * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia * 1  1/1609 (0.06%)  1/1614 (0.06%) 
Acquired hydrocele * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Balanoposthitis * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Acquired phimosis * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea * 1  0/1609 (0.00%)  2/1614 (0.12%) 
Chronic obstructive pulmonary disease * 1  5/1609 (0.31%)  6/1614 (0.37%) 
Epistaxis * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Atelectasis * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Pleural effusion * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Pneumonia aspiration * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Respiratory failure * 1  0/1609 (0.00%)  2/1614 (0.12%) 
Acute respiratory failure * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Idiopathic pulmonary fibrosis * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Pleurisy * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Pulmonary hypertension * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Acute pulmonary oedema * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Lung infiltration * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Organising pneumonia * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatitis * 1  0/1609 (0.00%)  2/1614 (0.12%) 
Eczema * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Toxic skin eruption * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Skin ulcer haemorrhage * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Surgical and medical procedures     
Eventration procedure * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Vascular disorders     
Hypovolaemic shock * 1  0/1609 (0.00%)  1/1614 (0.06%) 
Orthostatic hypotension * 1  1/1609 (0.06%)  0/1614 (0.00%) 
Haemorrhage * 1  1/1609 (0.06%)  0/1614 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDra 14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Dronedarone
Affected / at Risk (%) Affected / at Risk (%)
Total   38/1609 (2.36%)   100/1614 (6.20%) 
Gastrointestinal disorders     
Diarrhoea * 1  38/1609 (2.36%)  100/1614 (6.20%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDra 14.0
Given that the study was prematurely discontinued after 3236 patients were randomized (30% of the initial planned number), p-values were provided for information without any adjustment for multiplicity.
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 after trial completion, the investigator can present or publish trial results. A copy is submitted to the sponsor for review and comment at least 30 days in advance of any presentation or submission for publication.

The sponsor can require to delay the communication for a period not exceeding 90 days to allow for filing a patent application or such other measures as sponsor deems appropriate to establish and preserve its proprietary rights.

Results Point of Contact
Name/Title: Trial Transparency Team
Organization: sanofi-aventis
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01151137     History of Changes
Other Study ID Numbers: EFC11405
2010-019791-73 ( EudraCT Number )
U1111-1116-5566 ( Other Identifier: UTN )
First Submitted: June 22, 2010
First Posted: June 25, 2010
Results First Submitted: September 14, 2012
Results First Posted: October 26, 2012
Last Update Posted: October 26, 2012