Evaluating Ventricular Arrhythmia in Subjects With Implantable Cardioverter Defibrillator or Cardiac Resynchronization Therapy-Defibrillator
- Conditions
- Ventricular Arrhythmia
- Interventions
- Drug: EleclazineDrug: Placebo to match eleclazine
- Registration Number
- NCT02104583
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The primary objective of this study is to evaluate the effect of eleclazine (GS-6615) compared to placebo on the overall occurrence of appropriate implantable cardioverter-defibrillator (ICD) interventions (antitachycardia pacing \[ATP\] or shock) in adults with ICD or cardiac resynchronization therapy-defibrillator (CRT-D).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 313
- Have an ICD or CRT-D implanted for primary or secondary prevention and at least one ICD intervention for ventricular tachycardia/ventricular fibrillation (VT/VF) [shock or ATP] within 60 days prior to screening or a documented VT/VF episode (prior to implantation) within 60 days prior to screening
- Use of highly effective contraception methods if female of childbearing potential or sexually active male
- Must be hemodynamically stable
Key
- New York Heart Association (NYHA) Class IV heart failure
- Myocardial infarction, unstable angina, coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI) within 4 weeks prior to screening or during the screening period before randomization
- Hemodynamically significant primary obstructive valvular disease
- History of congenital heart disease
- Inherited arrhythmia such as Brugada syndrome. Individuals with long QT syndrome Type 3 (LQT-3) or hypertrophic cardiomyopathy (HCM) may be considered.
- Individuals who are being considered for cardiac transplantation and are on a cardiac transplant list
- History of seizures or epilepsy
- Cardiac ablation within 3 months prior to screening or planned cardiac ablation during the study
- Severe renal impairment
- Abnormal liver function tests
- Currently taking Class I and Class III antiarrhythmic drugs; such medications should be discontinued 5 half-lives (or 28 days for chronic use of amiodarone) prior to randomization
- Currently taking drugs or products that are strong inhibitors or inducers of CYP3A; such medications should be discontinued 5 half-lives prior to randomization
- Currently taking ranolazine; ranolazine should be discontinued at least 7 days prior to randomization
- Females who are pregnant or are breastfeeding
- Individuals with a subcutaneous ICD
- Body mass index (BMI) ≥ 36 kg/m^2
Note: Other protocol defined Inclusion/Exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Eleclazine 3 mg Eleclazine Participants will receive a single loading dose of eleclazine 30 mg on Day 1, followed by eleclazine 3 mg daily as maintenance for up to approximately 20 months. Eleclazine 6 mg Eleclazine Participants will receive a single loading dose of eleclazine 30 mg on Day 1, followed by eleclazine 6 mg daily as maintenance for up to approximately 20 months. Placebo Placebo to match eleclazine Participants will receive a single loading dose of placebo to match eleclazine on Day 1, followed by placebo to match eleclazine once daily for up to approximately 20 months.
- Primary Outcome Measures
Name Time Method Overall Occurrence (Total Number) of Appropriate Implantable Cardioverter-Defibrillator Device (ICD) Interventions (Anti-Tachycardia Pacing or Shock) Through Week 24 Randomization up to 24 weeks
- Secondary Outcome Measures
Name Time Method Overall Occurrence (Total Number) of Appropriate ICD Interventions (ATP or Shock) Through End of Study Randomization up to 22 months Change From Baseline in Premature Ventricular Complex (PVC) Count as Assessed by Continuous Electrocardiogram (cECG) Monitoring Baseline to Week 12 PVC count per 48 hours was obtained from cECG readings at Baseline and Week 12. Change in PVC from baseline was measured in units of number of episodes/48 hours. Change from baseline was calculated as the value at Week 12 minus the value at Baseline.
Time From First Dose of Study Drug to the First Occurrence of CV Hospitalization, Emergency Room (ER) Visit, or CV Death From first dose of study drug up to 22 months CV hospitalizations, CV ER visits, and CV deaths were determined through the adjudication by the CEC. The events that were adjudicated as undetermined were considered cardiovascular related. For each participant, the time from the first dose of study drug to the first CV hospitalization or CV ER visit through the last day on study or, in absence of CV hospitalizations or CV ER visits, to a CV death were derived as (first event date - first dose date + 1). The participants without CV hospitalizations, CV ER visits, or CV death were censored at the last day on study. As planned, data was reported only for Cohort 2 and combined Cohorts 1 and 2. Time to first occurrence of CV hospitalization, ER visit, or CV death was analyzed using KM estimates.
Change From Baseline in Nonsustained Ventricular Tachycardia (nsVT) Count as Assessed by Continuous cECG Monitoring Baseline to Week 12 The count of nsVTs per 48 hours was obtained from cECG readings at Baseline and Week 12. Change in nsVT from baseline was measured in units of number of episodes/48 hours. Change from baseline was calculated as the value at Week 12 minus the value at Baseline.
Overall Occurrence (Total Number) of Ventricular Tachycardia/Ventricular Fibrillation (VT/VF) (Treated or Untreated) Through Week 24 and End of Study Randomization up to Week 24; Randomization up to end of study (up to 22 months) Overall Occurrence (Total Number) of Electrical Storm Through Week 24 and End of Study Randomization up to Week 24; Randomization up to end of study (up to 22 months) An electrical storm was defined as ≥ 3 separate episodes of ventricular arrhythmia within a 24-hour period terminated by ICD.
Overall Occurrence (Total Number) of Inappropriate ICD Interventions Through Week 24 and End of Study Randomization up to Week 24; Randomization up to end of study (up to 22 months) Change in Left Ventricular Systolic and Diastolic Function as Assessed by Left Ventricular Ejection Fraction (LVEF) Baseline to Week 12; Baseline to Week 24 LVEF is a measure of how much blood is pumped out of the left ventricle of the heart. Change from baseline was calculated as the value at Week 12 or 24 minus the value at Baseline.
Time From First Dose of Study Drug to the First Occurrence of Appropriate ICD Interventions (ATP or Shock) or Cardiovascular (CV) Death From first dose of study drug up to 22 months CV deaths were determined through the adjudication by an external independent clinical event committee (CEC). The deaths that were adjudicated as undetermined were considered cardiovascular related. For each participant, the time from the first dose of study drug to the beginning of the earliest appropriate ICD intervention through the last day on study or, in absence of appropriate ICD interventions, to a CV death was derived as (first event date - first dose date + 1). The participants without appropriate ICD interventions or CV death were censored at the last day on study. As planned, data was reported only for Cohort 2 and combined Cohorts 1 and 2. Time to first occurrence of an appropriate ICD interventions or CV death was analyzed using Kaplan-Meier (KM) estimates.
Trial Locations
- Locations (84)
Cardiovascular Associates of Mesa
🇺🇸Mesa, Arizona, United States
Ohiohealth Corporation
🇺🇸Columbus, Ohio, United States
Charlotte Heart and Vascular Institute
🇺🇸Port Charlotte, Florida, United States
South Denver Cardiology Associates, PC
🇺🇸Littleton, Colorado, United States
Mid Michigan Medical Center - Midland
🇺🇸Midland, Michigan, United States
Magyar Honvedseg Egeszsegugyi Kozpont
🇭🇺Budapest, Hungary
Great Falls Clinic
🇺🇸Great Falls, Montana, United States
Florida Medical Clinic PA
🇺🇸Zephyrhills, Florida, United States
The Heart Institute at Largo
🇺🇸Largo, Florida, United States
Coastal Cardiology Consultants PA dba Heart and Vascular Institute of Florida
🇺🇸Clearwater, Florida, United States
Athens Regional Specialty Services
🇺🇸Athens, Georgia, United States
Capital Area Research
🇺🇸Camp Hill, Pennsylvania, United States
Radin Cardiovascular Medical Associates
🇺🇸Newport Beach, California, United States
Budai Irgalmasrendi Kórház
🇭🇺Budapest, Hungary
Long Beach Memorial Hospital
🇺🇸Long Beach, California, United States
University of Heidelberg
🇩🇪Heidelberg, Germany
Catharina ziekenhuis
🇳🇱Eindhoven, Netherlands
St.Antonius Hospital
🇳🇱Nieuwegein, Netherlands
State Hospital for Cardiology
🇭🇺Balatonfüred, Hungary
Medical University of Lodz
🇵🇱Lodz, Poland
Medical University Wroclaw
🇵🇱Wroclaw, Poland
Medizinische Klinik und Poliklinik I Abteilung für Kardiologie
🇩🇪Munich, Germany
New York Methodist Hospital
🇺🇸Brooklyn, New York, United States
Gemeinschaftspraxis für Innere Medizin
🇩🇪Riesa, Germany
HaEmek Medical Center
🇮🇱Afula, Israel
Kingston General Hospital
🇨🇦Kingston, Ontario, Canada
Onze Lieve Vrouwe Gasthuis
🇳🇱Amsterdam, Netherlands
Isala
🇳🇱Zwolle, Netherlands
Collegium Medicum Uniwersytetu Jagiellonskiego
🇵🇱Kraków, Poland
Indywidualna Specjalistyczna Praktyka Lekarska Jarosław Kaźmierczak
🇵🇱Szczecin, Poland
Warszawski Uniwersytet Medyczny
🇵🇱Warszawa, Poland
Chum Hotel Dieu
🇨🇦Montreal, Quebec, Canada
Tel Aviv University/Meir Medical Center
🇮🇱Israel, Israel
University Medical Center Goettingen
🇩🇪Goettingen, Germany
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Czechia
Charles University Hospital Královské Vinohrady
🇨🇿Prague, Czechia
Amphia ziekenhuis
🇳🇱Breda, Netherlands
Zala Megyei Kórház
🇭🇺Zalaegerszeg, Hungary
Sheba Medical Center
🇮🇱Ramat Gan, Israel
Galilee Medical Center
🇮🇱Nahariya, Israel
Kaplan Medical Center
🇮🇱Rehovot, Israel
Maastricht University Medical Center
🇳🇱Maastricht, Netherlands
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Mc Tronik Specjalistyczny Gabinet Kontroli Stymulatorow Serca Dr N. Med. Michal Chudzik
🇵🇱Lódz, Poland
NZOZ Sopockie Centrum badan Kardiolog.ProCordis pawel Miekus
🇵🇱Sopot, Poland
Samodzielny Publiczny Szpital Kliniczny nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach Górnosla
🇵🇱Katowice, Poland
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Instytut Kardiologii im Prymasa Tysiaclecia Kardynala Stefana Wyszynskiego
🇵🇱Warsaw, Poland
Aalborg University Hospital
🇩🇰Aalborg, Denmark
Rigshospitalet, The Heart Center
🇩🇰Copenhagen, Denmark
Gentofte Hospitak, Deparment of Cardiology
🇩🇰Hellerup, Denmark
Methodist Physicians Clinic Heart Consultants
🇺🇸Omaha, Nebraska, United States
Durham VA Medical Center
🇺🇸Durham, North Carolina, United States
Good Samaritan Hospital
🇺🇸Los Angeles, California, United States
Atlantic Clinical Research Collaborative
🇺🇸Atlantis, Florida, United States
Michigan Cardiovascular Institute
🇺🇸Saginaw, Michigan, United States
Aultman Hospital
🇺🇸Canton, Ohio, United States
West Houston Area Clinical Trial Consultants
🇺🇸Houston, Texas, United States
Care New England Health Care, Kent Hospital
🇺🇸Warwick, Rhode Island, United States
Stroobants Cardiovascular Center
🇺🇸Lynchburg, Virginia, United States
Virginia Heart Group Ltd
🇺🇸Falls Church, Virginia, United States
Odense University Hospital/Department of Cardiology
🇩🇰Odense C, Denmark
Klinikum der Universität Regensburg
🇩🇪Regensburg, Germany
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Indywidualna Specjalistyczna Praktyka Lekarska Andrzej Lubinski
🇵🇱Lódz, Poland
Szpital Wolski im Dr Anny Gostynskiej SP ZOZ
🇵🇱Warszawa, Poland
Clearwater Cardiovascular and Interventional Consultants
🇺🇸Clearwater, Florida, United States
CardioVascular Institute
🇺🇸Wormleysburg, Pennsylvania, United States
Cardiovascular Research Institute of Dallas
🇺🇸Dallas, Texas, United States
Centre Hospitalier Universitaire de Sherbrooke CHUS
🇨🇦Sherbrooke, Quebec, Canada
The University of Vermont Medical Center
🇺🇸Burlington, Vermont, United States
New Mexico Hear Institute
🇺🇸Albuquerque, New Mexico, United States
QEII Health Sciences Centre
🇨🇦Halifax, Canada
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Marshfield Clinic Research Foundation
🇺🇸Marshfield, Wisconsin, United States
Carilion Roanoke Memorial Hospital
🇺🇸Roanoke, Virginia, United States
Volunteer Research Group
🇺🇸Knoxville, Tennessee, United States
Vivantes Humboldt Klinikum
🇩🇪Berlin, Germany
Rambam Health Care Campus
🇮🇱Haifa, Israel
Regional Cardiology Associates
🇺🇸Sacramento, California, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Washington Adventist Hospital
🇺🇸Takoma Park, Maryland, United States
Seton Heart Institute
🇺🇸Austin, Texas, United States