Dose Ranging Study of Celivarone With Amiodarone as Calibrator for the Prevention of Implantable Cardioverter Defibrillator (ICD) Interventions or Death

Condition(s) targeted: Arrhythmia Prophylaxis

Intervention: Celivarone (SSR149744) (Drug); amiodarone (Drug); placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Sanofi-Aventis

Official(s) and/or principal investigator(s):
Peter KOWEY, Pr, Study Chair, Affiliation: Steering Committee Chair Person

Overall contact:
Public Registry ICD, Email: GV-Contact-us@sanofi-aventis.com

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.

Official title: Double Blind Placebo Controlled Dose Ranging Study of the Efficacy and Safety of Celivarone at 50, 100 or 300 mg OD With Amiodarone as Calibrator for the Prevention of ICD Interventions or Death

Study design: Prevention, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study

Primary outcome: Time to Ventricular Tachycardia or Ventricular Fibrillation (VT/VF) triggered ICD interventions or sudden death

Secondary outcome:

Time to ICD shocks or deaths

Time to Cardiovascular hospitalization or death

Detailed description: 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.

Minimum age: 21 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Public Registry ICD, Email: GV-Contact-us@sanofi-aventis.com

Sanofi-aventis Administrative Office, Macquarie Park, Australia; Recruiting

Sanofi-aventis Administrative Office, Praha, Czech Republic; Recruiting

Sanofi-aventis Administrative Office, Moscow, Russian Federation; Recruiting

Sanofi-aventis Administrative Office, Bridgewater, New Jersey 08807, United States; Recruiting

Starting date: September 2009
Ending date: July 2011
Last updated: October 19, 2009