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

A Randomized, International, Multi-center, Open-label Study to Document Optimal Timing of Initiation of Dronedarone Treatment After Conversion With Loading Dose of Amiodarone in Patients With Persistent Atrial Fibrillation Requiring Conversion of AF.

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.