Ranolazine Implantable Cardioverter-Defibrillator Trial (RAID)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Wojciech Zareba, University of Rochester
ClinicalTrials.gov Identifier:
NCT01215253
First received: September 30, 2010
Last updated: December 30, 2015
Last verified: December 2015
  Purpose
The purpose of the study is to see how effective a drug called ranolazine is in reducing the risk of ventricular arrhythmia and death in people with implantable cardioverter-defibrillators (ICDs). This drug will be used with standard medications that is routinely prescribed in enrolled patients.

Condition Intervention Phase
Ischemic Cardiomyopathy
Nonischemic Cardiomyopathy
Heart Failure
Drug: Ranolazine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: Late Sodium Current Blockade in High-Risk ICD Patients

Resource links provided by NLM:


Further study details as provided by University of Rochester:

Primary Outcome Measures:
  • Ventricular Tachycardia or Ventricular Fibrillation or Death [ Time Frame: 2 years of follow-up on average ] [ Designated as safety issue: Yes ]
    Primary endpoint of the study will be defined as a composite endpoint consisting of Ventricular Tachycardia or Ventricular Fibrillation requiring ATP therapy, ICD shock, or death, whichever occurs first


Secondary Outcome Measures:
  • Cardiac Hospitalization,ICD shock for VT or VF or Death [ Time Frame: 2 years of follow-up on average ] [ Designated as safety issue: Yes ]
    Cardiac hospitalization; ICD shock for VT or VF or death, whichever occurs first.


Enrollment: 1012
Study Start Date: September 2011
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ranolazine
At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at end of first week. For patients on anti-arrhythmic therapy at the time of randomization, their ECG will be checked at end of first week on 500 mg dose and again at end of second week on 1000 mg dose. For patients with CrCl <60ml/min prior to randomization, their CrCl will be checked again at 2 weeks and study drug discontinued if <30ml/min. For patients with CrCl <60ml/min at 2 weeks, their CrCl will be checked again at 4 weeks and study drug discontinued if <30ml/min.
Drug: Ranolazine
At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.
Other Name: Ranexa
Placebo Comparator: Placebo Drug: Ranolazine
At enrollment, patients will be randomized to ranolazine or placebo. In the active drug arm each patient will be started on a 500 mg twice a day dose for one week with subsequent increase to 1000 mg twice a day at beginning of second week.
Other Name: Ranexa

Detailed Description:

There are limited treatment options for patients at high risk of ventricular arrhythmic events. Beta-blockers alone do not provide enough protection, sotalol has limited effectiveness, and amiodarone although effective in some groups of patients is used infrequently due to its side effects and limitations of a long-term use. Ischemia and cardiomyopathies are associated with a sodium overload of myocardial cells. Late sodium current plays a pivotal role in this process. Sodium overload leads to calcium overload of myocardial cells with consequent increased vulnerability of myocardium to ventricular tachyarrhythmias as well as increased impairment of diastolic relaxation of myocardium thereby augmenting the risk of ischemia and myocardial damage.

Ranolazine is a novel drug with anti-ischemic and antiarrhythmic properties that uniquely blocks late sodium current, decreases intracellular calcium overload, and improves diastolic relaxation of the ventricles. The antiischemic and antiarrhythmic properties of ranolazine might decrease the likelihood of arrhythmic events and improve the clinical course of patients with ventricular arrhythmias.

We designed a randomized double-blind placebo-controlled clinical trial enrolling 1,440 high-risk ICD patients who will be treated with ranolazine or placebo in addition to optimal medical therapy to test the hypothesis that late sodium current blockade contributes to significant reduction in the risk of arrhythmic events or death in high-risk ICD/CRT-D patients.

  Eligibility

Ages Eligible for Study:   21 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

1,440 high-risk patients with ischemic/nonischemic cardiomyopathy who receive their ICDs as standard of care for primary or secondary prevention of mortality following approved indications for ICD therapy. High-risk patients will be defined as:

Secondary Prevention Patients Subjects with ischemic or nonischemic cardiomyopathy, qualified for or with existing ICD (or CRT-D) after documented VT/VF or cardiac arrest (secondary prevention of mortality). Secondary prevention subjects with existing implants are eligible regardless of when the implant was received (subjects could be recruited from outpatient clinics or from inpatient activity including during re-implant or other procedures).

Primary Prevention Patients

  1. Patients with primary prevention indications for ischemic or non-ischemic cardiomyopathy with EF≤35%, with existing devices (ICD/CRT-D), regardless of when the device was implanted, who have experienced at least ONE episode of VT/VF appropriately treated with ICD therapy (ATP or shock) or had untreated NSVT lasting at least 10 beats with heart rate of at least 170 bpm, documented by electrogram of their implanted device.
  2. Patients with ischemic or non-ischemic cardiomyopathy with EF≤35%, who have been implanted within the last 2 years (initial ICD/CRT-D implants, including upgrades from pacemakers) who have NOT experienced VT/VF treated with ICD therapy (ATP or shock), AND who have ONE of the following additional criteria: BUN≥26 mg/dl or QRS>120ms or Atrial Fibrillation or NSVT documented by ECG/Holter or >500 Ventricular Premature Beats (VPBs)documented in a 24-hour Holter.

    • Stable optimal pharmacologic therapy for the cardiac condition
    • Age: equal to 21 years without upper limit

Exclusion Criteria:

  • Patient receiving first device with coronary artery bypass graft surgery within the last 3 calendar months prior to date consent obtained
  • Patients receiving first device with percutaneous coronary intervention within the last 1 calendar month prior to date consent obtained
  • Patient receiving first device with enzyme-positive myocardial infarction with the past 3 calendar months prior to date consent obtained
  • Patient receiving first device with angiographic evidence of coronary disease who are candidates for coronary revascularization and are likely to undergo coronary artery bypass graft surgery or percutaneous coronary intervention in the foreseeable future
  • Patient in NYHA Class IV
  • Patients receiving prophylactic ablation of ventricular substrate
  • Patients with preexisting QTc prolongation >550ms
  • Patients on strong CYP3A inhibitors (including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir and saquinavir and moderate CYP3A inhibitors, including, diltiazem, verapamil, aprepitant, erythromycin, fluconazole and grapefruit juice or grapefruit-containing products.
  • Patients on CYP3A inducers such as rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine and St.John's wort
  • Patients with inherited arrhythmia disorders such as Brugada's, ARVD, LQTS or hypertrophic cardiomyopathy
  • Patient who is pregnant or plans to become pregnant during the course of the trial (patients at child bearing age who use prescribed pharmaceutical contraceptives could be enrolled)
  • Patient with irreversible brain damage from preexisting cerebral disease
  • Patient with presence of any disease, other than the patient's cardiac disease, associated with a reduced likelihood of survival for the duration of the trial, e.g., cancer, uremia, liver failure, etc.
  • Patient with chronic renal disease with creatinine >2.5 mg/dl or creatinine clearance <30 ml/min
  • Patient participating in any other clinical trial
  • Patient unwilling or unable to cooperate with the protocol
  • Patient who lives at such a distance from the clinic that travel for follow-up visits would be unusually difficult
  • Patient who does not anticipate being a resident of the area for the scheduled duration of the trial
  • Patients who are decisionally impaired adults, those of questionable capacity, and those who cannot consent for themselves will not be recruited for this study.
  • Patient unwilling to sign the consent for participation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01215253

  Hide Study Locations
Locations
United States, Arizona
University of Arizona
Tucson, Arizona, United States, 85724
United States, Arkansas
Arkansas Cardiology
Little Rock, Arkansas, United States, 72205
United States, California
Sequoia Hospital
E. Palo Alto, California, United States, 94303
Good Samaritan Hospital
Los Angeles, California, United States, 90017
Huntington Memorial Hospital
Pasadena, California, United States, 91105
Regional Cardiology Associates
Sacramento, California, United States, 95819
Delta Heart and Medical Clinic
Stockton, California, United States, 95210
United States, Colorado
University of Colorado Health - MHS
Colorado Springs, Colorado, United States, 80909
United States, Connecticut
Bridgeport Hospital
Bridgeport, Connecticut, United States, 06610
Hartford Hospital
Hartford, Connecticut, United States, 06102
United States, District of Columbia
Washington Electrophysiology/Cardiovascular Research Institute
Washington, District of Columbia, United States, 20010
United States, Florida
Bay Area Cardiology Associates, P.A.
Brandon, Florida, United States, 33511
University of Florida/Cardiovascular Medicine
Gainseville, Florida, United States, 32610
University of Florida Health Science Center at Jacksonville
Jacksonville, Florida, United States, 32209
Watson Clincia Center for Research Inc.
Lakeland, Florida, United States, 33805
Florida Hospital
Orlando, Florida, United States, 32803
Tallahassee Research Institute, Inc.
Tallahassee, Florida, United States, 32308
United States, Georgia
Georgia Health Sciences University
Augusta, Georgia, United States, 30912
Georgia Arrhythmia Consultants
Macon, Georgia, United States, 31201
United States, Illinois
University of Chicago Hospital
Chicago, Illinois, United States, 60637
United States, Indiana
Peakview Research Center
Fort Wayne, Indiana, United States, 46845
LaPorte Hospital
Hobart, Indiana, United States, 46342
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Kentucky
Central Baptist Hospital
Lexington, Kentucky, United States, 40503
United States, Louisiana
Louisiana State University Health Sciences Center- New Orleans
New Orleans, Louisiana, United States, 70112
United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
Johns Hopkins University
Baltimore, Maryland, United States, 21287
MedStar Southern Maryland Hospital Center
Clinton, Maryland, United States, 20735
United States, Massachusetts
Tufts-New England Medical Center
Boston, Massachusetts, United States, 02111
Lahey Clinic
Burlington, Massachusetts, United States, 01805
University of Massachusetts-Worchester
Worcester, Massachusetts, United States, 01655
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
William Beaumont Hospital - Royal Oak
Royal Oak, Michigan, United States, 48073
Michigan Heart
Ypsilanti, Michigan, United States, 48197
United States, Minnesota
St. Luke's Hospital Association of Duluth
Duluth, Minnesota, United States, 55805
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Missouri
University of Missouri
Columbia, Missouri, United States, 65212
Kansas City Heart Foundation
Kansas City, Missouri, United States, 64114
United States, New Jersey
Cooper University Hospital
Camden, New Jersey, United States, 08043
Morristown Memorial Hospital- Gagnon Cardiovascular Institute
Morristown, New Jersey, United States, 07962
United States, New York
SUNY Downstate Medical Center
Brooklyn, New York, United States, 11203
New York Methodist Hospital
Brooklyn, New York, United States, 11215
Maimonides Medical Center
Brooklyn, New York, United States, 11219
Weill Cornell Medical College/New York Presbyterian Hospital
New York, New York, United States, 10021
St. Luke's-Roosevelt Hospital
New York, New York, United States, 10025
Hudson Valley Heart Center
Poughkeepsie, New York, United States, 12601
The Valley Hospital
Ridgewood, New York, United States, 07450
University of Rochester
Rochester, New York, United States, 14642
Stony Brook University Medical Center,
Stony Brook, New York, United States, 11794
United States, North Carolina
Durham VA Medical Center
Durham, North Carolina, United States, 27705
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
The Lindner Center for Research & Education
Cincinnati, Ohio, United States, 45219
University of Cincinnati
Cincinnati, Ohio, United States, 45267
The MetroHealth System - Heart and Vascular Dept.
Cleveland, Ohio, United States, 44109
The Toledo Hospital/Northwest Ohio Cardiology Consultants
Toledo, Ohio, United States, 43615
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
Portland VA Medical Ctr
Portland, Oregon, United States, 97239
United States, Pennsylvania
Abington Medical Specialists
Abington, Pennsylvania, United States, 19001
Doylestown Cardiology Associates - VIAA
Doylestown, Pennsylvania, United States, 18901
Doylestown Health Cardiology/Central Bucks
Doylestown, Pennsylvania, United States, 18901
Lancaster Heart & Stroke Foundation
Lancaster, Pennsylvania, United States, 17602
Drexel University College of Medicine
Philadelphia, Pennsylvania, United States, 19102
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
University of Pittsburgh Medical Center-Presbyterian
Pittsburgh, Pennsylvania, United States, 15213
VA Pittsburgh Healthcare Center
Pittsburgh, Pennsylvania, United States, 15240
Lankenau Institute for Medical Research
Wynnewood, Pennsylvania, United States, 19096
United States, Rhode Island
Brigham and Women's Cardiovascular Associates
Warwick, Rhode Island, United States, 02886
United States, Tennessee
The Stern Cardiovascular Center
Germantown, Tennessee, United States, 38138
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
Texas Cardiac Arrhythmia Research Foundation
Austin, Texas, United States, 78705
Cardiopulmonary Research Science and Technology Inst.
Dallas, Texas, United States, 75230
Medicus Alliance CRO, Inc
Houston, Texas, United States, 77090
United States, Virginia
University of Virginia Health System
Charlottesville, Virginia, United States, 22908
Cardiovascular Associates Ltd.
Chesapeake, Virginia, United States, 23320
Walter Reed NMMC
Portsmouth, Virginia, United States, 20889
Virginia Commonwealth University
Richmond, Virginia, United States, 23219
United States, Washington
Kootenai Heart Clinics, LLC
Spokane, Washington, United States, 99204
Cardiac Study Center
Tacoma, Washington, United States, 98405
United States, West Virginia
CAMC Institute
Charleston, West Virginia, United States, 25304
United States, Wisconsin
Marshfield Clinic
Marshfield, Wisconsin, United States, 54449
Aurora St. Luke's Medical Center
Milwaukee, Wisconsin, United States, 53215
Wheaton Franciscan All Saints
Racine, Wisconsin, United States, 53402
Canada, Alberta
University of Calgary
Calgary, Alberta, Canada, T2N 4Z6
Royal Alexandra Hospital
Edmonton, Alberta, Canada, T5H 3V9
Canada, Ontario
Queen's University
Kingston, Ontario, Canada, K7L 2V7
Canada, Quebec
Montreal Heart Institute
Montreal, Quebec, Canada, H1T 1C8
McGill University Health Centre
Montreal, Quebec, Canada, H3G1A4
CHUS (Sherbrooke University)
Sherbrooke, Quebec, Canada, J1H5N4
Canada
IUCPQ
Quebec, Canada, G1V 4G5
Sponsors and Collaborators
University of Rochester
Investigators
Principal Investigator: Wojciech Zareba, MD PhD University of Rochester
  More Information

Responsible Party: Wojciech Zareba, MD PhD, University of Rochester
ClinicalTrials.gov Identifier: NCT01215253     History of Changes
Other Study ID Numbers: U01HL096607 
Study First Received: September 30, 2010
Last Updated: December 30, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by University of Rochester:
Sudden Death
Ranolazine
Heart failure
Ventricular tachycardia
Ventricular fibrillation
Implantable cardioverter-defibrillator

Additional relevant MeSH terms:
Heart Failure
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases
Ranolazine
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 25, 2016