NCT01215253

Brief Summary

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,012

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Sep 2011

Longer than P75 for phase_3

Geographic Reach
2 countries

90 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 30, 2010

Completed
6 days until next milestone

First Posted

Study publicly available on registry

October 6, 2010

Completed
11 months until next milestone

Study Start

First participant enrolled

September 1, 2011

Completed
5.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 28, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2017

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

June 15, 2018

Completed
Last Updated

August 27, 2018

Status Verified

July 1, 2018

Enrollment Period

5.5 years

First QC Date

September 30, 2010

Results QC Date

May 24, 2018

Last Update Submit

July 27, 2018

Conditions

Keywords

Sudden DeathRanolazineHeart failureVentricular tachycardiaVentricular fibrillationImplantable cardioverter-defibrillator

Outcome Measures

Primary Outcomes (1)

  • Number of Patients With Ventricular Tachycardia (VT) or Ventricular Fibrillation (VF) or Death

    Primary endpoint of the study will be defined as a composite endpoint consisting of Ventricular Tachycardia or Ventricular Fibrillation requiring antitachycardia pacing (ATP) therapy, implantable cardioverter-defibrillator (ICD) shock, or death, whichever occurs first.

    2 years of follow-up on average

Secondary Outcomes (9)

  • Number of Patients With VT or VF Requiring ICD Shock or Death

    2 years of follow-up on average

  • Number of Recurrent Episodes of VT or VF Requiring Antitachycardia Pacing (ATP) or ICD Shock Therapies

    2 years of follow-up on average

  • Number of Patients With First Inappropriate ICD Shock

    2 years of follow-up on average

  • Number of Patients With Hospitalization for Cardiac Causes or Death, Whichever Occurred First.

    2 years of follow-up on average

  • Number of Patients With Heart Failure Hospitalization or Death, Whichever Occurred First

    2 years of follow-up on average

  • +4 more secondary outcomes

Other Outcomes (2)

  • Number of Patients Whose First VT/VF Required Antitachycardia Pacing (ATP)

    2 years of follow-up on average

  • Number of Patients Whose First VT/VF Required ICD Shock

    2 years of follow-up on average

Study Arms (2)

Ranolazine

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Interventions

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.

Also known as: Ranexa
PlaceboRanolazine

Eligibility Criteria

Age21 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ,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
  • 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.
  • 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

You may not qualify if:

  • 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
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (90)

University of Arizona

Tucson, Arizona, 85724, United States

Location

Arkansas Cardiology

Little Rock, Arkansas, 72205, United States

Location

Sequoia Hospital

East Palo Alto, California, 94303, United States

Location

Good Samaritan Hospital

Los Angeles, California, 90017, United States

Location

Huntington Memorial Hospital

Pasadena, California, 91105, United States

Location

Regional Cardiology Associates

Sacramento, California, 95819, United States

Location

Delta Heart and Medical Clinic

Stockton, California, 95210, United States

Location

University of Colorado Health - MHS

Colorado Springs, Colorado, 80909, United States

Location

Bridgeport Hospital

Bridgeport, Connecticut, 06610, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Washington Electrophysiology/Cardiovascular Research Institute

Washington D.C., District of Columbia, 20010, United States

Location

Bay Area Cardiology Associates, P.A.

Brandon, Florida, 33511, United States

Location

University of Florida/Cardiovascular Medicine

Gainesville, Florida, 32610, United States

Location

University of Florida Health Science Center at Jacksonville

Jacksonville, Florida, 32209, United States

Location

Watson Clincia Center for Research Inc.

Lakeland, Florida, 33805, United States

Location

Florida Hospital

Orlando, Florida, 32803, United States

Location

Tallahassee Research Institute, Inc.

Tallahassee, Florida, 32308, United States

Location

Georgia Health Sciences University

Augusta, Georgia, 30912, United States

Location

Georgia Arrhythmia Consultants

Macon, Georgia, 31201, United States

Location

University of Chicago Hospital

Chicago, Illinois, 60637, United States

Location

Peakview Research Center

Fort Wayne, Indiana, 46845, United States

Location

LaPorte Hospital

Hobart, Indiana, 46342, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Central Baptist Hospital

Lexington, Kentucky, 40503, United States

Location

Louisiana State University Health Sciences Center- New Orleans

New Orleans, Louisiana, 70112, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

MedStar Southern Maryland Hospital Center

Clinton, Maryland, 20735, United States

Location

Tufts-New England Medical Center

Boston, Massachusetts, 02111, United States

Location

Lahey Clinic

Burlington, Massachusetts, 01805, United States

Location

University of Massachusetts-Worchester

Worcester, Massachusetts, 01655, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

William Beaumont Hospital - Royal Oak

Royal Oak, Michigan, 48073, United States

Location

Michigan Heart

Ypsilanti, Michigan, 48197, United States

Location

St. Luke's Hospital Association of Duluth

Duluth, Minnesota, 55805, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

University of Missouri

Columbia, Missouri, 65212, United States

Location

Kansas City Heart Foundation

Kansas City, Missouri, 64114, United States

Location

Cooper University Hospital

Camden, New Jersey, 08043, United States

Location

Morristown Memorial Hospital- Gagnon Cardiovascular Institute

Morristown, New Jersey, 07962, United States

Location

SUNY Downstate Medical Center

Brooklyn, New York, 11203, United States

Location

New York Methodist Hospital

Brooklyn, New York, 11215, United States

Location

Maimonides Medical Center

Brooklyn, New York, 11219, United States

Location

Weill Cornell Medical College/New York Presbyterian Hospital

New York, New York, 10021, United States

Location

St. Luke's-Roosevelt Hospital

New York, New York, 10025, United States

Location

Hudson Valley Heart Center

Poughkeepsie, New York, 12601, United States

Location

The Valley Hospital

Ridgewood, New York, 07450, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Stony Brook University Medical Center,

Stony Brook, New York, 11794, United States

Location

Durham VA Medical Center

Durham, North Carolina, 27705, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Lindner Center for Research & Education

Cincinnati, Ohio, 45219, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

The MetroHealth System - Heart and Vascular Dept.

Cleveland, Ohio, 44109, United States

Location

The Toledo Hospital/Northwest Ohio Cardiology Consultants

Toledo, Ohio, 43615, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Portland VA Medical Ctr

Portland, Oregon, 97239, United States

Location

Abington Medical Specialists

Abington, Pennsylvania, 19001, United States

Location

Doylestown Cardiology Associates - VIAA

Doylestown, Pennsylvania, 18901, United States

Location

Doylestown Health Cardiology/Central Bucks

Doylestown, Pennsylvania, 18901, United States

Location

Lancaster Heart & Stroke Foundation

Lancaster, Pennsylvania, 17602, United States

Location

Drexel University College of Medicine

Philadelphia, Pennsylvania, 19102, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center-Presbyterian

Pittsburgh, Pennsylvania, 15213, United States

Location

VA Pittsburgh Healthcare Center

Pittsburgh, Pennsylvania, 15240, United States

Location

Lankenau Institute for Medical Research

Wynnewood, Pennsylvania, 19096, United States

Location

Brigham and Women's Cardiovascular Associates

Warwick, Rhode Island, 02886, United States

Location

The Stern Cardiovascular Center

Germantown, Tennessee, 38138, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Texas Cardiac Arrhythmia Research Foundation

Austin, Texas, 78705, United States

Location

Cardiopulmonary Research Science and Technology Inst.

Dallas, Texas, 75230, United States

Location

Medicus Alliance CRO, Inc

Houston, Texas, 77090, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Cardiovascular Associates Ltd.

Chesapeake, Virginia, 23320, United States

Location

Walter Reed NMMC

Portsmouth, Virginia, 20889, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23219, United States

Location

Kootenai Heart Clinics, LLC

Spokane, Washington, 99204, United States

Location

Cardiac Study Center

Tacoma, Washington, 98405, United States

Location

CAMC Institute

Charleston, West Virginia, 25304, United States

Location

Marshfield Clinic

Marshfield, Wisconsin, 54449, United States

Location

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

Wheaton Franciscan All Saints

Racine, Wisconsin, 53402, United States

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

Royal Alexandra Hospital

Edmonton, Alberta, T5H 3V9, Canada

Location

Queen's University

Kingston, Ontario, K7L 2V7, Canada

Location

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

McGill University Health Centre

Montreal, Quebec, H3G1A4, Canada

Location

CHUS (Sherbrooke University)

Sherbrooke, Quebec, J1H5N4, Canada

Location

IUCPQ

Québec, G1V 4G5, Canada

Location

Related Publications (3)

  • Krzowski B, Kutyifa V, Vloka M, Huang DT, Attari M, Aktas M, Shah AH, Musat D, Rosenthal L, McNitt S, Polonsky B, Schuger C, Natale A, Ziv O, Beck C, Daubert JP, Goldenberg I, Zareba W. Sex-Related Differences in Ventricular Tachyarrhythmia Events in Patients With Implantable Cardioverter-Defibrillator and Prior Ventricular Tachyarrhythmias. JACC Clin Electrophysiol. 2024 Feb;10(2):284-294. doi: 10.1016/j.jacep.2023.09.028. Epub 2023 Nov 29.

  • Younis A, Goldenberg I, Farooq S, Yavin H, Daubert J, Raitt M, Mazur A, Huang DT, Mitchell BL, Rashtian MR, Winters S, Vloka M, Aktas M, Bernabei MA, Beck CA, McNitt S, Zareba W. Reduction in Ventricular Tachyarrhythmia Burden in Patients Enrolled in the RAID Trial. JACC Clin Electrophysiol. 2022 Jun;8(6):754-762. doi: 10.1016/j.jacep.2022.02.018. Epub 2022 Apr 27.

  • Zareba W, Daubert JP, Beck CA, Huang DT, Alexis JD, Brown MW, Pyykkonen K, McNitt S, Oakes D, Feng C, Aktas MK, Ayala-Parades F, Baranchuk A, Dubuc M, Haigney M, Mazur A, McPherson CA, Mitchell LB, Natale A, Piccini JP, Raitt M, Rashtian MY, Schuger C, Winters S, Worley SJ, Ziv O, Moss AJ; RAID Trial Investigators. Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillators: The RAID Trial. J Am Coll Cardiol. 2018 Aug 7;72(6):636-645. doi: 10.1016/j.jacc.2018.04.086.

MeSH Terms

Conditions

Heart FailureDeath, SuddenTachycardia, VentricularVentricular Fibrillation

Interventions

Ranolazine

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular DiseasesDeathPathologic ProcessesPathological Conditions, Signs and SymptomsTachycardiaArrhythmias, CardiacCardiac Conduction System Disease

Intervention Hierarchy (Ancestors)

AcetanilidesAnilidesAmidesOrganic ChemicalsAniline CompoundsAminesPiperazinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Results Point of Contact

Title
Wojciech Zareba
Organization
University of Rochester

Study Officials

  • Wojciech Zareba, MD PhD

    University of Rochester

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD PhD

Study Record Dates

First Submitted

September 30, 2010

First Posted

October 6, 2010

Study Start

September 1, 2011

Primary Completion

February 28, 2017

Study Completion

February 28, 2017

Last Updated

August 27, 2018

Results First Posted

June 15, 2018

Record last verified: 2018-07

Data Sharing

IPD Sharing
Will not share

The RAID PI and Steering Committee with investigators from enrolling sites have designed a series of secondary substudies that will be disseminated as abstracts and manuscripts. External proposal of analyses of the RAID trial data will be reviewed bye the Steering Committee and analyses will be conducted by the Data Coordinating Center (DCC) of the trial.

Locations