Clinical trial NCT00993382: Dose Ranging Study of Celivarone With Amiodarone as Calibrator for the Prevention of Implantable Cardioverter Defibrillator (ICD) Interventions or Death
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Arrhythmia Prophylaxis
Ventricular Arrhythmia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2009-10-12
Enrollment: 486
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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 Celivarone plasma levels during the study.

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 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 anti-tachycardia 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.

Primary outcomes:
measure: Time to Ventricular Tachycardia or Ventricular Fibrillation (VT/VF) triggered ICD interventions or sudden death
timeFrame: up to 20 months (median follow-up of 12 months)
Secondary outcomes:
measure: Time to ICD shocks (appropriate or inappropriate) or death from any cause
timeFrame: up to 20 months (median follow-up of 12 months)
measure: Time to Cardiovascular hospitalization or death
timeFrame: up to 20 months (median follow-up of 12 months)
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Investigational Site Number 840006
state: Alabama
city: Mobile
country: United States
facility: Investigational Site Number 840042
state: Alabama
city: Mesa
country: United States
facility: Investigational Site Number 840014
state: Arizona
city: Phoenix
country: United States
facility: Investigational Site Number 840032
state: Arizona
city: Tucson
country: United States
facility: Investigational Site Number 840033
state: Arizona
city: Redondo Beach
country: United States
facility: Investigational Site Number 840054
state: California
city: Redwood City
country: United States
facility: Investigational Site Number 840007
state: California
city: Colorado Springs
country: United States
facility: Investigational Site Number 840039
state: Colorado
city: Fort Myers
country: United States
facility: Investigational Site Number 840002
state: Florida
city: Orlando
country: United States
facility: Investigational Site Number 840010
state: Florida
city: Port Charlotte
country: United States
facility: Investigational Site Number 840005
state: Florida
city: St. Petersburg
country: United States
facility: Investigational Site Number 840013
state: Florida
city: St. Petersburg
country: United States
facility: Investigational Site Number 840043
state: Florida
city: Augusta
country: United States
facility: Investigational Site Number 840004
state: Georgia
city: Chicago
country: United States
facility: Investigational Site Number 840045
state: Illinois
city: Lombard
country: United States
facility: Investigational Site Number 840035
state: Illinois
city: Kansas City
country: United States
facility: Investigational Site Number 840017
state: Kansas
city: Scarborough
country: United States
facility: Investigational Site Number 840022
state: Maine
city: Ann Arbor
country: United States
facility: Investigational Site Number 840009
state: Michigan
city: Detroit
country: United States
facility: Investigational Site Number 840026
state: Michigan
city: Petoskey
country: United States
facility: Investigational Site Number 840003
state: Michigan
city: Ypsilanti
country: United States
facility: Investigational Site Number 840015
state: Michigan
city: Columbia
country: United States
facility: Investigational Site Number 840049
state: Missouri
city: Kansas City
country: United States
facility: Investigational Site Number 840019
state: Missouri
city: New York
country: United States
facility: Investigational Site Number 840031
state: New York
city: Tulsa
country: United States
facility: Investigational Site Number 840029
state: Oklahoma
city: Portland
country: United States
facility: Investigational Site Number 840037
state: Oregon
city: Camp Hill
country: United States
facility: Investigational Site Number 840024
state: Pennsylvania
city: Doylestown
country: United States
facility: Investigational Site Number 840030
state: Pennsylvania
city: Upland
country: United States
facility: Investigational Site Number 840034
state: Pennsylvania
city: Charleston
country: United States
facility: Investigational Site Number 840020
state: South Carolina
city: Rapid City
country: United States
facility: Investigational Site Number 840048
state: South Dakota
city: Tullahoma
country: United States
facility: Investigational Site Number 840011
state: Tennessee
city: Chesapeake
country: United States
facility: Investigational Site Number 840025
state: Virginia
city: Norfolk
country: United States
facility: Investigational Site Number 840012
state: Virginia
city: Richmond
country: United States
facility: Investigational Site Number 840038
state: Virginia
city: Spokane
country: United States
facility: Investigational Site Number 840016
state: Washington
city: Ciudad Autonoma De Bs.As
country: Argentina
facility: Investigational Site Number 032002
city: Corrientes
country: Argentina
facility: Investigational Site Number 032003
city: San Miguel De Tucuman
country: Argentina
facility: Investigational Site Number 032004
city: Adelaide
country: Australia
facility: Investigational Site Number 036012
city: Auchenflower
country: Australia
facility: Investigational Site Number 036006
city: Bedford Park
country: Australia
facility: Investigational Site Number 036004
city: Camperdown
country: Australia
facility: Investigational Site Number 036014
city: Garran
country: Australia
facility: Investigational Site Number 036013
city: Gosford
country: Australia
facility: Investigational Site Number 036010
city: Herston
country: Australia
facility: Investigational Site Number 036005
city: Nedlands
country: Australia
facility: Investigational Site Number 036008
city: New Lambton
country: Australia
facility: Investigational Site Number 036009
city: Perth
country: Australia
facility: Investigational Site Number 036007
city: Woolloongabba
country: Australia
facility: Investigational Site Number 036003
city: Aalst
country: Belgium
facility: Investigational Site Number 056005
city: Brugge
country: Belgium
facility: Investigational Site Number 056007
city: Brussel
country: Belgium
facility: Investigational Site Number 056001
city: Gilly
country: Belgium
facility: Investigational Site Number 056002
city: Hasselt
country: Belgium
facility: Investigational Site Number 056004
city: Roeselare
country: Belgium
facility: Investigational Site Number 056003
city: Calgary
country: Canada
facility: Investigational Site Number 124009
city: Hamilton
country: Canada
facility: Investigational Site Number 124010
city: London
country: Canada
facility: Investigational Site Number 124004
city: Montreal
country: Canada
facility: Investigational Site Number 124008
city: Montreal
country: Canada
facility: Investigational Site Number 124001
city: Ste-Foy
country: Canada
facility: Investigational Site Number 124005
city: Toronto
country: Canada
facility: Investigational Site Number 124002
city: Vancouver
country: Canada
facility: Investigational Site Number 124006
city: Victoria
country: Canada
facility: Investigational Site Number 124007
city: Santiago
country: Chile
facility: Investigational Site Number 152001
city: Brno
country: Czech Republic
facility: Investigational Site Number 203004
city: Ceske Budejovice
country: Czech Republic
facility: Investigational Site Number 203002
city: Hradec Kralove
country: Czech Republic
facility: Investigational Site Number 203005
city: Liberec
country: Czech Republic
facility: Investigational Site Number 203001
city: Olomouc
country: Czech Republic
facility: Investigational Site Number 203003
city: Praha 5
country: Czech Republic
facility: Investigational Site Number 203006
city: Aarhus
country: Denmark
facility: Investigational Site Number 208002
city: Hellerup
country: Denmark
facility: Investigational Site Number 208004
city: København Ø
country: Denmark
facility: Investigational Site Number 208005
city: Odense C
country: Denmark
facility: Investigational Site Number 208001
city: Helsinki
country: Finland
facility: Investigational Site Number 246001
city: Tampere
country: Finland
facility: Investigational Site Number 246004
city: Brest
country: France
facility: Investigational Site Number 250004
city: Grenoble
country: France
facility: Investigational Site Number 250006
city: Lille
country: France
facility: Investigational Site Number 250005
city: Montpellier
country: France
facility: Investigational Site Number 250002
city: Paris Cedex 15
country: France
facility: Investigational Site Number 250001
city: Rennes
country: France
facility: Investigational Site Number 250007
city: Vandoeuvre Les Nancy Cedex
country: France
facility: Investigational Site Number 250003
city: Bad Neustadt
country: Germany
facility: Investigational Site Number 276005
city: Bernau
country: Germany
facility: Investigational Site Number 276002
city: Dresden
country: Germany
facility: Investigational Site Number 276003
city: Frankfurt Am Main
country: Germany
facility: Investigational Site Number 276001
city: Hamburg
country: Germany
facility: Investigational Site Number 276006
city: Balatonfüred
country: Hungary
facility: Investigational Site Number 348001
city: Budapest
country: Hungary
facility: Investigational Site Number 348004
city: Pécs
country: Hungary
facility: Investigational Site Number 348005
city: Zalaegerszeg
country: Hungary
facility: Investigational Site Number 348003
city: Afula
country: Israel
facility: Investigational Site Number 376002
city: Ashkelon
country: Israel
facility: Investigational Site Number 376003
city: Haifa
country: Israel
facility: Investigational Site Number 376004
city: Tel Aviv
country: Israel
facility: Investigational Site Number 376001
city: Bari
country: Italy
facility: Investigational Site Number 380004
city: Bergamo
country: Italy
facility: Investigational Site Number 380008
city: Como
country: Italy
facility: Investigational Site Number 380002
city: Firenze
country: Italy
facility: Investigational Site Number 380001
city: Roma
country: Italy
facility: Investigational Site Number 380007
city: Meguro-Ku
country: Japan
facility: Investigational Site Number 392004
city: Niigata-Shi
country: Japan
facility: Investigational Site Number 392005
city: Osaka Sayama-Shi
country: Japan
facility: Investigational Site Number 392001
city: Osaka-Shi
country: Japan
facility: Investigational Site Number 392006
city: Shinjuku-Ku
country: Japan
facility: Investigational Site Number 392003
city: Suita-Shi
country: Japan
facility: Investigational Site Number 392002
city: Mexico City
country: Mexico
facility: Investigational Site Number 484002
city: Alkmaar
country: Netherlands
facility: Investigational Site Number 528001
city: Amsterdam
country: Netherlands
facility: Investigational Site Number 528005
city: Breda
country: Netherlands
facility: Investigational Site Number 528002
city: Maastricht
country: Netherlands
facility: Investigational Site Number 528003
city: Rotterdam
country: Netherlands
facility: Investigational Site Number 528007
city: Zwolle
country: Netherlands
facility: Investigational Site Number 528004
city: Drammen
country: Norway
facility: Investigational Site Number 578003
city: Bydgoszcz
country: Poland
facility: Investigational Site Number 616007
city: Gdynia
country: Poland
facility: Investigational Site Number 616011
city: Lodz
country: Poland
facility: Investigational Site Number 616006
city: Lodz
country: Poland
facility: Investigational Site Number 616003
city: Szczecin
country: Poland
facility: Investigational Site Number 616002
city: Warszawa
country: Poland
facility: Investigational Site Number 616008
city: Warszawa
country: Poland
facility: Investigational Site Number 616001
city: Coimbra
country: Portugal
facility: Investigational Site Number 620004
city: Lisboa
country: Portugal
facility: Investigational Site Number 620003
city: Vila Nova De Gaia
country: Portugal
facility: Investigational Site Number 620005
city: Ekaterinburg
country: Russian Federation
facility: Investigational Site Number 643006
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643005
city: Samara
country: Russian Federation
facility: Investigational Site Number 643008
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643003
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643011
city: Tomsk
country: Russian Federation
facility: Investigational Site Number 643004
city: Tyumen
country: Russian Federation
facility: Investigational Site Number 643007
city: Bratislava
country: Slovakia
facility: Investigational Site Number 703001
city: Kosice
country: Slovakia
facility: Investigational Site Number 703002
city: Pretoria
country: South Africa
facility: Investigational Site Number 710002
city: Barcelona
country: Spain
facility: Investigational Site Number 724001
city: Barcelona
country: Spain
facility: Investigational Site Number 724002
city: Madrid
country: Spain
facility: Investigational Site Number 724004
city: Madrid
country: Spain
facility: Investigational Site Number 724003
city: Santiago De Compostela
country: Spain
facility: Investigational Site Number 724006
city: Sevilla
country: Spain
facility: Investigational Site Number 724009
city: Valencia
country: Spain
facility: Investigational Site Number 724007
city: Stockholm
country: Sweden
facility: Investigational Site Number 752002
city: Umeå
country: Sweden
facility: Investigational Site Number 752003
city: Uppsala
country: Sweden
facility: Investigational Site Number 752001
city: Ankara
country: Turkey
facility: Investigational Site Number 792001
city: Istanbul
country: Turkey
facility: Investigational Site Number 792003
city: Istanbul
country: Turkey
facility: Investigational Site Number 792002
Study officials:
affiliation: Steering Committee Chair Person
name: Peter KOWEY, Pr
role: STUDY_CHAIR
References:
citation: 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.