Optimal Timing of Dronedarone Initiation After Conversion in Patients With Persistent Atrial Fibrillation
Optimal Timing of Dronedarone Initiation After Conversion in Patients With Persistent Atrial Fibrillation
Primary Objective:

 - Evaluate the rate of Atrial Fibrillation (AF) recurrences one month after randomization
 according to different timings of initiation of dronedarone.

 Secondary Objective:

 -  Evaluate the rate of AF recurrences two months after randomization.

 -  Assess the safety of the change from amiodarone to dronedarone

 -  Assess dronedarone safety

 -  Explore dronedarone and its active metabolite plasma level (in a subset of countries)

 -  Explore potential Pharmacokinetic (PK) interaction between dronedarone and amiodarone
 (in a subset of countries)
Inclusion criteria:

 Screening:

 -  Persistent AF for more than 72 hours (documented by an ECG taken within the last 72
 hours) for whom cardioversion, anti-arrhythmic treatment and anticoagulation treatment
 are indicated in the opinion of the Investigator

 -  Naive of amiodarone treatment in the last three months

 -  QTc Bazett < 500 ms on 12-lead ECG,

 -  At least one cardiovascular risk factor (i.e. age > 70, hypertension, diabetes, prior
 cerebrovascular disease or left atrial diameter >= 50 mm

 Randomization:

 -  Outpatient and Inpatients (except patients hospitalized during screening period for
 SAE)

 -  Sinus rhythm

 -  Effective oral anticoagulation verified by International Normalized Ratio/INR (target
 > 2)

 -  QTc Bazett < 500 ms and PR < 280 ms on 12-lead ECG

 -  Completed treatment period with amiodarone (28 days ± 2 days)

 Exclusion criteria:

 Screening:

 -  Contraindication to oral anticoagulation

 -  Acute condition known to cause AF

 -  Permanent AF

 -  Paroxysmal AF

 -  Bradycardia < 50 bpm on the 12-lead ECG

 -  Clinically overt congestive heart failure:

 -  with New York Heart Association (NYHA) classes III and IV heart failure

 -  with LVEF < 35%

 -  or NYHA class II with a recent decompensation requiring hospitalization or
 referral to a specialized heart failure clinic

 -  or unstable hemodynamic conditions

 -  Severe hepatic impairment

 -  Previous treatment with class I or class III anti-arrhythmic drugs (including sotalol)
 if taken less than one week

 -  Previous history of amiodarone intolerance or toxicity

 -  Any contraindication as per dronedarone and amiodarone labelling

 -  Wolff-Parkinson-White Syndrome

 -  Previous ablation for atrial fibrillation or any planned ablation in the next 2 months

 -  Contraindicated concomitant treatment:

 -  Potent cytochrome P450 (CYP3A4) inhibitors

 -  Use of drugs or herbal products that prolong the QT interval and known to
 increase the risk of Torsades de Pointes

 -  Class I or III anti-arrhythmic drugs (including sotalol)

 Randomization:

 -  Bradycardia < 50 bpm on the 12-lead ECG

 -  Clinically overt congestive heart failure:

 -  with New York Heart Association (NYHA) classes III and IV heart failure

 -  with LVEF < 35%

 -  or NYHA class II with a recent decompensation requiring hospitalization or
 referral to a specialized heart failure clinic

 -  or unstable hemodynamic conditions

 -  Severe hepatic impairment

 -  Previous treatment with class I or class III anti-arrhythmic drugs (including sotalol)
 if taken less than one week

 -  Patient in whom the following contraindicated concomitant treatment is mandatory:

 -  Potent cytochrome P450 (CYP3A4) inhibitors

 -  Use of drugs or herbal products that prolong the QT interval and known to
 increase the risk of Torsades de Pointes

 -  Class I or III anti-arrhythmic drugs (including sotalol)

 The above information is not intended to contain all considerations relevant to a patient's
 potential participation in a clinical trial.