Dose Ranging Study of Celivarone With Amiodarone as Calibrator for the Prevention of Implantable Cardioverter Defibrillator (ICD) Interventions or Death (ALPHEE)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
The Primary Objective was to assess the efficacy of celivarone for the prevention of Implantable Cardioverter Defibrillator (ICD) interventions or death.
Secondary Objectives were:
- 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Arrhythmia Prophylaxis Ventricular Arrhythmia |
Drug: Celivarone (SSR149744) Drug: amiodarone Drug: placebo |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Prevention |
| 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 |
- Time to Ventricular Tachycardia or Ventricular Fibrillation (VT/VF) triggered ICD interventions or sudden death [ Time Frame: up to 20 months (median follow-up of 12 months) ] [ Designated as safety issue: No ]
The presence of VT or VF was documented by ICD interrogation leading to any ICD interventions (shocks or antittachycardia pacing).
The 10 first ICD interventions for each patient were centrally and blindly adjudicated by an Adjudication Committee.
- Time to ICD shocks (appropriate or inappropriate) or death from any cause [ Time Frame: up to 20 months (median follow-up of 12 months) ] [ Designated as safety issue: No ]
- Time to Cardiovascular hospitalization or death [ Time Frame: up to 20 months (median follow-up of 12 months) ] [ Designated as safety issue: No ]
| Enrollment: | 486 |
| Study Start Date: | September 2009 |
| Study Completion Date: | May 2011 |
| Primary Completion Date: | May 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: celivarone 50 mg
Celivarone 50 mg capsule once daily up to 10-15 days before the common study end date
|
Drug: Celivarone (SSR149744)
50 or 100 mg capsules oral administration with a meal Matching capsules oral administration with a meal |
|
Experimental: celivarone 100 mg
Celivarone 100 mg once daily up to 10-15 days before the common study end date
|
Drug: Celivarone (SSR149744)
50 or 100 mg capsules oral administration with a meal Matching capsules oral administration with a meal |
|
Experimental: celivarone 300 mg
Celivarone 300 mg once daily up to 10-15 days before the common study end date
|
Drug: Celivarone (SSR149744)
50 or 100 mg capsules oral administration with a meal |
|
Active Comparator: amiodarone 200 mg
Amiodarone 600 mg once daily for 10 days (loading dose) then 200 mg once daily up to 10-15 days before the common study end date
|
Drug: amiodarone
200 mg capsules oral administration with a meal Matching capsules oral administration with a meal |
|
Placebo Comparator: placebo
Placebo once daily up to 10-15 days before the common study end date
|
Drug: placebo
Matching capsules oral administration with a meal |
Detailed Description:
The study included a one week screening period, followed by a treatment period ranging between 6 and 19 months.
The treatment was to be continued until the End of Treatment visit scheduled 10-15 days prior to the common Scheduled Study End Date (SSED). The SSED was defined as about 190 days after the last patient randomization date.
The expected recruitment duration was about 14 months and thus the total duration of the study about 20 months. Visits were 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.
Eligibility| Ages Eligible for Study: | 21 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations
Show 151 Study Locations| Study Chair: | Peter KOWEY, Pr | Steering Committee Chair Person |
More Information
Publications:
| Responsible Party: | Sanofi |
| ClinicalTrials.gov Identifier: | NCT00993382 History of Changes |
| Other Study ID Numbers: | DRI10936, 2008-008412-47 |
| Study First Received: | October 9, 2009 |
| Last Updated: | May 7, 2012 |
| Health Authority: | United States: Food and Drug Administration Belgium: Federal Agency for Medicinal Products and Health Products |
Additional relevant MeSH terms:
|
Arrhythmias, Cardiac Heart Diseases Cardiovascular Diseases Pathologic Processes Amiodarone Anti-Arrhythmia Agents |
Cardiovascular Agents Therapeutic Uses Pharmacologic Actions Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Vasodilator Agents |
ClinicalTrials.gov processed this record on May 19, 2013