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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00993382
First received: October 9, 2009
Last updated: October 12, 2013
Last verified: October 2013

October 9, 2009
October 12, 2013
September 2009
May 2011   (final data collection date for primary outcome measure)
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 Ventricular Tachycardia or Ventricular Fibrillation (VT/VF) triggered ICD interventions or sudden death [ Time Frame: up to 20 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00993382 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Time to ICD shocks or deaths [ Time Frame: up to 20 months ] [ Designated as safety issue: No ]
  • Time to Cardiovascular hospitalization or death [ Time Frame: up to 20 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Dose Ranging Study of Celivarone With Amiodarone as Calibrator for the Prevention of Implantable Cardioverter Defibrillator (ICD) Interventions or Death
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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • Arrhythmia Prophylaxis
  • Ventricular Arrhythmia
  • Drug: Celivarone (SSR149744)

    50 or 100 mg capsules

    oral administration with a meal

  • Drug: amiodarone

    200 mg capsules

    oral administration with a meal

  • Drug: placebo

    Matching capsules

    oral administration with a meal

  • Experimental: celivarone 50 mg
    Celivarone 50 mg capsule once daily up to 10-15 days before the common study end date
    Interventions:
    • Drug: Celivarone (SSR149744)
    • Drug: placebo
  • Experimental: celivarone 100 mg
    Celivarone 100 mg once daily up to 10-15 days before the common study end date
    Interventions:
    • Drug: Celivarone (SSR149744)
    • Drug: placebo
  • Experimental: celivarone 300 mg
    Celivarone 300 mg once daily up to 10-15 days before the common study end date
    Intervention: Drug: Celivarone (SSR149744)
  • 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
    Interventions:
    • Drug: amiodarone
    • Drug: placebo
  • Placebo Comparator: placebo
    Placebo once daily up to 10-15 days before the common study end date
    Intervention: Drug: placebo
Kowey PR, Crijns HJ, Aliot EM, Capucci A, Kulakowski P, Radzik D, Roy D, Connolly SJ, Hohnloser SH; ALPHEE Study Investigators. Efficacy and safety of celivarone, with amiodarone as calibrator, in patients with an implantable cardioverter-defibrillator for prevention of implantable cardioverter-defibrillator interventions or death: the ALPHEE study. Circulation. 2011 Dec 13;124(24):2649-60. doi: 10.1161/CIRCULATIONAHA.111.072561. Epub 2011 Nov 14.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
486
May 2011
May 2011   (final data collection date for primary outcome measure)

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.

Both
21 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Australia,   Belgium,   Canada,   Chile,   Czech Republic,   Denmark,   Finland,   France,   Germany,   Hungary,   Israel,   Italy,   Japan,   Mexico,   Netherlands,   Norway,   Poland,   Portugal,   Russian Federation,   Slovakia,   South Africa,   Spain,   Sweden,   Turkey,   United States
 
NCT00993382
DRI10936, 2008-008412-47
Yes
Sanofi
Sanofi
Not Provided
Study Chair: Peter KOWEY, Pr Steering Committee Chair Person
Sanofi
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP