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

NCT00993382 | Completed Phase 2 DMC

• 2 other identifiers: DRI109362008-008412-47
• Study Type: interventional
• Target: 486
• Locations: 26 countries
• Sites: 151

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.

Conditions

Arrhythmia Prophylaxis; Ventricular Arrhythmia

Outcome Measures

Primary Outcomes (1)

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

  The presence of VT or VF was documented by ICD interrogation leading to any ICD interventions (shocks or anti-tachycardia pacing). The 10 first ICD interventions for each patient were centrally and blindly adjudicated by an Adjudication Committee.

  up to 20 months (median follow-up of 12 months)

Secondary Outcomes (2)

• Time to ICD shocks (appropriate or inappropriate) or death from any cause

  up to 20 months (median follow-up of 12 months)

• Time to Cardiovascular hospitalization or death

  up to 20 months (median follow-up of 12 months)

Study Arms (5)

Celivarone 50 mg

EXPERIMENTAL

Celivarone, 50 mg once daily up to 10-15 days before the common study end date

Drug: Celivarone; Drug: Matching placebo

Celivarone 100 mg

EXPERIMENTAL

Celivarone, 100 mg once daily up to 10-15 days before the common study end date

Drug: Celivarone; Drug: Matching placebo

Celivarone 300 mg

EXPERIMENTAL

Celivarone, 300 mg once daily up to 10-15 days before the common study end date

Drug: Celivarone; Drug: Matching placebo

Amiodarone

ACTIVE COMPARATOR

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; Drug: Matching placebo

Placebo

PLACEBO COMPARATOR

Matching placebo once daily up to 10-15 days before the common study end date

Drug: Matching placebo

Interventions

Celivarone DRUG

Pharmaceutical form: capsule Route of administration: oral

Also known as: SSR149744

Celivarone 100 mg; Celivarone 300 mg; Celivarone 50 mg

Amiodarone DRUG

Pharmaceutical form: capsule Route of administration: oral

Also known as: Cordarone

Amiodarone

Matching placebo DRUG

Pharmaceutical form: capsule Route of administration: oral Matching placebo added to active drug if any for a total of 3 capsules per intake

Amiodarone; Celivarone 100 mg; Celivarone 300 mg; Celivarone 50 mg; Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (151)

Investigational Site Number 840006

Huntsville, Alabama, 35801, United States

Location

Investigational Site Number 840042

Mobile, Alabama, 36608, United States

Location

Investigational Site Number 840014

Mesa, Arizona, 85206, United States

Location

Investigational Site Number 840032

Phoenix, Arizona, 85006, United States

Location

Investigational Site Number 840033

Tucson, Arizona, 85723, United States

Location

Investigational Site Number 840054

Redondo Beach, California, 90277, United States

Location

Investigational Site Number 840007

Redwood City, California, 94062, United States

Location

Investigational Site Number 840039

Colorado Springs, Colorado, 80909, United States

Location

Investigational Site Number 840002

Fort Myers, Florida, 33908, United States

Location

Investigational Site Number 840010

Orlando, Florida, 32806, United States

Location

Investigational Site Number 840005

Port Charlotte, Florida, 33952-8008, United States

Location

Investigational Site Number 840013

St. Petersburg, Florida, 33707, United States

Location

Investigational Site Number 840043

St. Petersburg, Florida, 33707, United States

Location

Investigational Site Number 840004

Augusta, Georgia, 30901, United States

Location

Investigational Site Number 840045

Chicago, Illinois, 60637, United States

Location

Investigational Site Number 840035

Lombard, Illinois, 60148, United States

Location

Investigational Site Number 840017

Kansas City, Kansas, 66160, United States

Location

Investigational Site Number 840022

Scarborough, Maine, 04074, United States

Location

Investigational Site Number 840009

Ann Arbor, Michigan, 48109-0759, United States

Location

Investigational Site Number 840026

Detroit, Michigan, 48236, United States

Location

Investigational Site Number 840003

Petoskey, Michigan, 49770, United States

Location

Investigational Site Number 840015

Ypsilanti, Michigan, 48197, United States

Location

Investigational Site Number 840049

Columbia, Missouri, 65201, United States

Location

Investigational Site Number 840019

Kansas City, Missouri, 64114, United States

Location

Investigational Site Number 840031

New York, New York, 10001, United States

Location

Investigational Site Number 840029

Tulsa, Oklahoma, 74104, United States

Location

Investigational Site Number 840037

Portland, Oregon, 97201-3098, United States

Location

Investigational Site Number 840024

Camp Hill, Pennsylvania, 17011, United States

Location

Investigational Site Number 840030

Doylestown, Pennsylvania, 18901, United States

Location

Investigational Site Number 840034

Upland, Pennsylvania, 19013, United States

Location

Investigational Site Number 840020

Charleston, South Carolina, 29406, United States

Location

Investigational Site Number 840048

Rapid City, South Dakota, 57701, United States

Location

Investigational Site Number 840011

Tullahoma, Tennessee, 37388, United States

Location

Investigational Site Number 840025

Chesapeake, Virginia, 23320, United States

Location

Investigational Site Number 840012

Norfolk, Virginia, 23507, United States

Location

Investigational Site Number 840038

Richmond, Virginia, 23225, United States

Location

Investigational Site Number 840016

Spokane, Washington, 99204, United States

Location

Investigational Site Number 032002

Ciudad Autonoma de Bs.As, 1428, Argentina

Location

Investigational Site Number 032003

Corrientes, 3400, Argentina

Location

Investigational Site Number 032004

San Miguel de Tucumán, T4000NIL, Argentina

Location

Investigational Site Number 036012

Adelaide, 5000, Australia

Location

Investigational Site Number 036006

Auchenflower, 4066, Australia

Location

Investigational Site Number 036004

Bedford Park, 5042, Australia

Location

Investigational Site Number 036014

Camperdown, 2050, Australia

Location

Investigational Site Number 036013

Garran, 2605, Australia

Location

Investigational Site Number 036010

Gosford, 2250, Australia

Location

Investigational Site Number 036005

Herston, 4029, Australia

Location

Investigational Site Number 036008

Nedlands, 6009, Australia

Location

Investigational Site Number 036009

New Lambton, 2305, Australia

Location

Investigational Site Number 036007

Perth, 6000, Australia

Location

Investigational Site Number 036003

Woolloongabba, 4102, Australia

Location

Investigational Site Number 056005

Aalst, 9300, Belgium

Location

Investigational Site Number 056007

Bruges, 8000, Belgium

Location

Investigational Site Number 056001

Brussels, 1090, Belgium

Location

Investigational Site Number 056002

Gilly, 6060, Belgium

Location

Investigational Site Number 056004

Hasselt, 3500, Belgium

Location

Investigational Site Number 056003

Roeselare, 8800, Belgium

Location

Investigational Site Number 124009

Calgary, T2N 2T9, Canada

Location

Investigational Site Number 124010

Hamilton, L8L 2X2, Canada

Location

Investigational Site Number 124004

London, N6A 5A5, Canada

Location

Investigational Site Number 124008

Montreal, H1T 1C8, Canada

Location

Investigational Site Number 124001

Montreal, H2W 1T8, Canada

Location

Investigational Site Number 124005

Ste-Foy, G1V 4G5, Canada

Location

Investigational Site Number 124002

Toronto, M5B 1W8, Canada

Location

Investigational Site Number 124006

Vancouver, V6E 1M9, Canada

Location

Investigational Site Number 124007

Victoria, V8R 4R2, Canada

Location

Investigational Site Number 152001

Santiago, 8380456, Chile

Location

Investigational Site Number 203004

Brno, 65691, Czechia

Location

Investigational Site Number 203002

České Budějovice, 37087, Czechia

Location

Investigational Site Number 203005

Hradec Králové, 50005, Czechia

Location

Investigational Site Number 203001

Liberec, 46063, Czechia

Location

Investigational Site Number 203003

Olomouc, 77520, Czechia

Location

Investigational Site Number 203006

Prague, 15030, Czechia

Location

Investigational Site Number 208002

Aarhus, 8200, Denmark

Location

Investigational Site Number 208004

Hellerup, 2900, Denmark

Location

Investigational Site Number 208005

København Ø, 2100, Denmark

Location

Investigational Site Number 208001

Odense C, 5000, Denmark

Location

Investigational Site Number 246001

Helsinki, 00290, Finland

Location

Investigational Site Number 246004

Tampere, 33520, Finland

Location

Investigational Site Number 250004

Brest, 29609, France

Location

Investigational Site Number 250006

Grenoble, 38043, France

Location

Investigational Site Number 250005

Lille, 59037, France

Location

Investigational Site Number 250002

Montpellier, 34295, France

Location

Investigational Site Number 250001

Paris, 75908, France

Location

Investigational Site Number 250007

Rennes, 35033, France

Location

Investigational Site Number 250003

Vandœuvre-lès-Nancy, 54511, France

Location

Investigational Site Number 276005

Bad Neustadt an der Saale, 97616, Germany

Location

Investigational Site Number 276002

Bernau, 16321, Germany

Location

Investigational Site Number 276003

Dresden, 01099, Germany

Location

Investigational Site Number 276001

Frankfurt am Main, 60590, Germany

Location

Investigational Site Number 276006

Hamburg, 20246, Germany

Location

Investigational Site Number 348001

Balatonfüred, 8230, Hungary

Location

Investigational Site Number 348004

Budapest, 1027, Hungary

Location

Investigational Site Number 348005

Pécs, 7624, Hungary

Location

Investigational Site Number 348003

Zalaegerszeg, 8900, Hungary

Location

Investigational Site Number 376002

Afula, 18101, Israel

Location

Investigational Site Number 376003

Ashkelon, 78278, Israel

Location

Investigational Site Number 376004

Haifa, 31048, Israel

Location

Investigational Site Number 376001

Tel Aviv, 64239, Israel

Location

Investigational Site Number 380004

Bari, 70124, Italy

Location

Investigational Site Number 380008

Bergamo, 24125, Italy

Location

Investigational Site Number 380002

Como, 22100, Italy

Location

Investigational Site Number 380001

Florence, 50141, Italy

Location

Investigational Site Number 380007

Roma, 00169, Italy

Location

Investigational Site Number 392004

Meguro-Ku, Japan

Location

Investigational Site Number 392005

Niigata, Japan

Location

Investigational Site Number 392006

Osaka, Japan

Location

Investigational Site Number 392001

Osaka Sayama-Shi, Japan

Location

Investigational Site Number 392003

Shinjuku-Ku, Japan

Location

Investigational Site Number 392002

Suita-Shi, Japan

Location

Investigational Site Number 484002

Mexico City, 14080, Mexico

Location

Investigational Site Number 528001

Alkmaar, 1815 JD, Netherlands

Location

Investigational Site Number 528005

Amsterdam, 1091 AC, Netherlands

Location

Investigational Site Number 528002

Breda, 4818 CK, Netherlands

Location

Investigational Site Number 528003

Maastricht, 6229 HX, Netherlands

Location

Investigational Site Number 528007

Rotterdam, 3015 CE, Netherlands

Location

Investigational Site Number 528004

Zwolle, 8011 JW, Netherlands

Location

Investigational Site Number 578003

Drammen, 3004, Norway

Location

Investigational Site Number 616007

Bydgoszcz, 85-094, Poland

Location

Investigational Site Number 616011

Gdynia, 81-348, Poland

Location

Investigational Site Number 616006

Lodz, 90-548, Poland

Location

Investigational Site Number 616003

Lodz, 91-425, Poland

Location

Investigational Site Number 616002

Szczecin, 70-111, Poland

Location

Investigational Site Number 616008

Warsaw, 02-097, Poland

Location

Investigational Site Number 616001

Warsaw, 04-073, Poland

Location

Investigational Site Number 620004

Coimbra, 3000-075, Portugal

Location

Investigational Site Number 620003

Lisbon, 1169-024, Portugal

Location

Investigational Site Number 620005

Vila Nova de Gaia, 4430-502, Portugal

Location

Investigational Site Number 643005

Moscow, 650002, Russia

Location

Investigational Site Number 643003

Saint Petersburg, 197110, Russia

Location

Investigational Site Number 643011

Saint Petersburg, 199106, Russia

Location

Investigational Site Number 643008

Samara, 443070, Russia

Location

Investigational Site Number 643004

Tomsk, 634012, Russia

Location

Investigational Site Number 643007

Tyumen, 625023, Russia

Location

Investigational Site Number 643006

Yekaterinburg, 620102, Russia

Location

Investigational Site Number 703001

Bratislava, 81104, Slovakia

Location

Investigational Site Number 703002

Košice, 04011, Slovakia

Location

Investigational Site Number 710002

Pretoria, 181, South Africa

Location

Investigational Site Number 724001

Barcelona, 08036, Spain

Location

Investigational Site Number 724002

Barcelona, 08907, Spain

Location

Investigational Site Number 724004

Madrid, 28035, Spain

Location

Investigational Site Number 724003

Madrid, 28046, Spain

Location

Investigational Site Number 724006

Santiago de Compostela, 15706, Spain

Location

Investigational Site Number 724009

Seville, 41008, Spain

Location

Investigational Site Number 724007

Valencia, 46026, Spain

Location

Investigational Site Number 752002

Stockholm, 118 83, Sweden

Location

Investigational Site Number 752003

Umeå, 901 85, Sweden

Location

Investigational Site Number 752001

Uppsala, 751 85, Sweden

Location

Investigational Site Number 792001

Ankara, 06490, Turkey (Türkiye)

Location

Investigational Site Number 792003

Istanbul, 34304, Turkey (Türkiye)

Location

Investigational Site Number 792002

Istanbul, 34390, Turkey (Türkiye)

Location

Related Publications (1)

• 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.

  PMID: 22082672 RESULT

MeSH Terms

Interventions

celivarone; Amiodarone

Intervention Hierarchy (Ancestors)

Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Peter KOWEY, Pr

  Steering Committee Chair Person

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2009
• First Posted: October 12, 2009
• Study Start: September 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: May 30, 2016

Record last verified: 2016-05

Locations

SL (2); NL (6); DE (5); CZ (6); FI (2); JP (6); PL (7); SE (3); AU (11); ME (1); US (37); BE (6); NO (1); DK (4); HU (4); TU (3); IL (4); RU (7); CA (9); CL (1); FR (7); ZA (1); ES (7); IT (5); AR (3); PT (3)