The Primary Objective is to assess the efficacy of celivarone for the prevention of Implantable Cardioverter Defibrillator (ICD) interventions or death.

Secondary Objectives:

• To assess the tolerability and safety of the different dose regimens of celivarone in the selected population.
• To document SSR149744 plasma levels during the study.

The study includes a one week screening period, followed by a treatment period scheduled for a minimum duration of 6 months for the last patient recruited.

The treatment period is going from the first day of treatment to the End of Treatment visit to be done 10-15 days prior to the Scheduled Study End Date (SSED). The SSED is expected to be about 190 days after the last patient randomization date.

The expected recruitment duration is about 14 months and thus the total duration of the study about 20 months. Visits are planned to be performed at baseline, after 5 days, after 14 days, every month for 6 months and then, every three months after 6 months until the end of the study.

• Drug: Celivarone (SSR149744)

  Pharmaceutical form:capsules

  oral administration

• Drug: amiodarone

  Pharmaceutical form:capsules

  oral administration

• Drug: placebo

  Pharmaceutical form:capsules

  oral administration

• celivarone 50 mg od: Experimental
  Celivarone 50 mg once daily taken with a meal
  Intervention: Drug: Celivarone (SSR149744)
• celivarone 100 mg od: Experimental
  Celivarone 100 mg once daily taken with a meal
  Intervention: Drug: Celivarone (SSR149744)
• celivarone 300 mg od: Experimental
  Celivarone 300 mg once daily taken with a meal
  Intervention: Drug: Celivarone (SSR149744)
• amiodarone 600 mg/200 mg od: Active Comparator
  600 mg once daily for 10 days (calibrator loading dose period) then 200 mg once daily taken with a meal
  Intervention: Drug: amiodarone
• placebo: Placebo Comparator
  undistinguishable with the experimental drug or the calibrator placebo capsules taken with a meal
  Intervention: Drug: placebo

Inclusion criteria :

• Implantable Cardioverter Defibrillator (ICD) patients with a Left Ventricular Ejection Fraction (LVEF) of 40% or less AND one of the following criteria:

  • at least one ICD therapy for Ventricular Tachycardia (VT) OR
  • Ventricular Fibrillation (VF) in the previous month OR
  • ICD implantation in the previous month for documented VT/VF

Exclusion criteria :

• Patients of either sex aged below 21 years (or the age of legal consent of the country),
• Women of childbearing potential without adequate birth control or pregnant or breastfeeding women
• Patients with known ICD lead problem (lead dislodgement)

• ICD without the following characteristics :

  • data logging function with cumulative counting of device intervention (shocks and antitachycardia pacing [ATP])
  • electrogram storage capabilities
  • ventricular demand pacing.
• Recent unstable angina pectoris or myocardial infarction (< 4 weeks),
• History of torsades de pointes,
• Genetic channelopathies including congenital long QT syndrome,
• Wolff-Parkinson-White syndrome,
• Patients in unstable hemodynamic condition such as acute pulmonary edema within 12 hours prior to start of study medication; cardiogenic shock; treatment with intravenous pressor agents; patients on respirator; congestive heart failure of stage New York Heart Association (NYHA) IV within the last 4 weeks; uncorrected, hemodynamically significant primary obstructive valvular disease; hemodynamically significant obstructive cardiomyopathy; a cardiac operation or revascularization procedure within 4 weeks preceding randomization,
• Incessant sustained VT/VF (VT/VF that recurs promptly despite termination attempts) during the three days preceding randomization.
• Patients with inappropriate (not triggered by VT nor VF) shocks during the month preceding randomization.
• Clinically relevant haematologic, hepatobiliary (ALT, AST > 3 times the upper limit of normal at randomization), gastro-intestinal, renal (serum creatinine > 221 µmol/l (2.5 mg/dl) at randomization), pulmonary, endocrinologic or psychiatric disease.
• Patients treated with oral amiodarone (more than 20 tablets during the 2 months preceding randomization)

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