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

Study Overview
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Brief Summary
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Primary Objective: Demonstrate the efficacy of Dronedarone in preventing major cardiovascular events (stroke, systemic arterial embolism, myocardial infarction or cardiovascular death) or unplanned cardiovascular hospitalization or death from any cause in patients with permanent Atrial Fibrillation [AF] and additional risk factors Secondary Objective: Demonstrate the efficacy of Dronedarone in preventing cardiovascular death This was an event-driven study where a common study end date [CSED] was to be determined by Steering Committee based on the number of events (stroke, systemic arterial embolism, myocardial infarction or cardiovascular death).

Detailed Description
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The study period per participant was variable depending on the enrollment in the study. A final follow-up visit had to occur within 1 month after the CSED.

Official Title
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A Randomized, Double Blind, Placebo Controlled, Parallel Group Trial for Assessing the Clinical Benefit of Dronedarone 400mg BID on Top of Standard Therapy in Patients With Permanent Atrial Fibrillation and Additional Risk Factors

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: Dronedarone
* Drug: Placebo (for Dronedarone)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Permanent AF defined by the presence of all of the following criteria: Availability of one 12-lead ECG not more than 14 days prior to randomization showing that the patient is in AF or atrial flutter; Availability of documentation (including either rhythm strips or medical report of the rhythm) showing that the patient was in AF or atrial flutter at least 6 months prior to randomization; No evidence of sinus rhythm in the period between these two documentations of AF; Decision of the patient and physician to allow AF to continue without further efforts to restore sinus rhythm. At least one of the following risk criteria: Coronary artery disease; Prior stroke or Transient Ischemic Attack [TIA]; Symptomatic heart failure; Left ventricular ejection fraction [LVEF] less or equal to 0.40; Peripheral arterial occlusive disease; Aged 75 years or older with both hypertension and diabetes mellitus. Exclusion criteria: Paroxysmal AF; Persistent AF without a decision to allow AF to continue without further efforts to restore sinus rhythm; Heart failure of New-York Heart Association [NYHA] class IV or recent unstable NYHA class III. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dronedarone<br>Dronedarone 400 mg twice a day until the CSED | Drug: Dronedarone<br>* Film-coated tablet Oral administration under fed conditions (during breakfast and dinner)<br>* Other names: SR33589;|
| Placebo Comparator: placebo<br>Placebo (for Dronedarone) twice a day until the CSED | Drug: Placebo (for Dronedarone)<br>* film-coated tablet strictly identical in appearance Oral administration under fed conditions (during breakfast and dinner)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overview of the Two Co-primary Outcomes | 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. | From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year) | 
| Time to First Co-primary Outcome (Cumulative Incidence Function) | 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. | From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year) | 
| Time to Second Co-primary Outcome (Cumulative Incidence Function) | 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. | From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Deaths | Deaths were classified according to the primary cause of death. | From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year) | 
| Time to Cardiovascular Death (Cumulative Incidence Function) | 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. | From randomization up to the CSED which occurred at study termination (maximum follow-up of 1 year) |