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)


Eligibility Criteria:
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.