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Ischemic CardiomyopathyPhase 3RAIDNCT01215253

Ranolazine Implantable Cardioverter-Defibrillator Trial

A Phase 3 study testing Ranolazine in people with Ischemic Cardiomyopathy and Nonischemic Cardiomyopathy, run by University of Rochester at 90 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 21 years and older
What is being tested?
Ranolazine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,012 participants
Where
90 sitesin 2 countries
Study dates
Sep 2011to 28 Feb 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • 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

Who cannot join

  • 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
Show all 20Show fewer
  • 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

Trial locations and contacts

90 sites in 2 countries.

90 sites in 2 countries

United States83 sites

  • Abington Medical Specialists

    Abington, Pennsylvania, 19001

  • Georgia Health Sciences University

    Augusta, Georgia, 30912

  • Texas Cardiac Arrhythmia Research Foundation

    Austin, Texas, 78705

  • University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • Tufts-New England Medical Center

    Boston, Massachusetts, 02111

  • Bay Area Cardiology Associates, P.A.

    Brandon, Florida, 33511

  • Bridgeport Hospital

    Bridgeport, Connecticut, 06610

  • SUNY Downstate Medical Center

    Brooklyn, New York, 11203

  • New York Methodist Hospital

    Brooklyn, New York, 11215

  • Maimonides Medical Center

    Brooklyn, New York, 11219

  • Lahey Clinic

    Burlington, Massachusetts, 01805

  • Cooper University Hospital

    Camden, New Jersey, 08043

  • CAMC Institute

    Charleston, West Virginia, 25304

  • University of Virginia Health System

    Charlottesville, Virginia, 22908

  • Cardiovascular Associates Ltd.

    Chesapeake, Virginia, 23320

  • University of Chicago Hospital

    Chicago, Illinois, 60637

  • The Lindner Center for Research & Education

    Cincinnati, Ohio, 45219

  • University of Cincinnati

    Cincinnati, Ohio, 45267

  • The MetroHealth System - Heart and Vascular Dept.

    Cleveland, Ohio, 44109

  • MedStar Southern Maryland Hospital Center

    Clinton, Maryland, 20735

  • University of Colorado Health - MHS

    Colorado Springs, Colorado, 80909

  • University of Missouri

    Columbia, Missouri, 65212

  • Cardiopulmonary Research Science and Technology Inst.

    Dallas, Texas, 75230

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Doylestown Cardiology Associates - VIAA

    Doylestown, Pennsylvania, 18901

  • Doylestown Health Cardiology/Central Bucks

    Doylestown, Pennsylvania, 18901

  • St. Luke's Hospital Association of Duluth

    Duluth, Minnesota, 55805

  • Durham VA Medical Center

    Durham, North Carolina, 27705

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Sequoia Hospital

    East Palo Alto, California, 94303

  • Peakview Research Center

    Fort Wayne, Indiana, 46845

  • University of Florida/Cardiovascular Medicine

    Gainesville, Florida, 32610

  • The Stern Cardiovascular Center

    Germantown, Tennessee, 38138

  • Hartford Hospital

    Hartford, Connecticut, 06102

  • LaPorte Hospital

    Hobart, Indiana, 46342

  • Medicus Alliance CRO, Inc

    Houston, Texas, 77090

  • University of Iowa

    Iowa City, Iowa, 52242

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • University of Florida Health Science Center at Jacksonville

    Jacksonville, Florida, 32209

  • Kansas City Heart Foundation

    Kansas City, Missouri, 64114

  • Watson Clincia Center for Research Inc.

    Lakeland, Florida, 33805

  • Lancaster Heart & Stroke Foundation

    Lancaster, Pennsylvania, 17602

  • Central Baptist Hospital

    Lexington, Kentucky, 40503

  • Arkansas Cardiology

    Little Rock, Arkansas, 72205

  • Good Samaritan Hospital

    Los Angeles, California, 90017

  • Georgia Arrhythmia Consultants

    Macon, Georgia, 31201

  • Marshfield Clinic

    Marshfield, Wisconsin, 54449

  • Aurora St. Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Morristown Memorial Hospital- Gagnon Cardiovascular Institute

    Morristown, New Jersey, 07962

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Louisiana State University Health Sciences Center- New Orleans

    New Orleans, Louisiana, 70112

  • Weill Cornell Medical College/New York Presbyterian Hospital

    New York, New York, 10021

  • St. Luke's-Roosevelt Hospital

    New York, New York, 10025

  • Florida Hospital

    Orlando, Florida, 32803

  • Huntington Memorial Hospital

    Pasadena, California, 91105

  • Drexel University College of Medicine

    Philadelphia, Pennsylvania, 19102

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • University of Pittsburgh Medical Center-Presbyterian

    Pittsburgh, Pennsylvania, 15213

  • VA Pittsburgh Healthcare Center

    Pittsburgh, Pennsylvania, 15240

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • Portland VA Medical Ctr

    Portland, Oregon, 97239

  • Walter Reed NMMC

    Portsmouth, Virginia, 20889

  • Hudson Valley Heart Center

    Poughkeepsie, New York, 12601

  • Wheaton Franciscan All Saints

    Racine, Wisconsin, 53402

  • Virginia Commonwealth University

    Richmond, Virginia, 23219

  • The Valley Hospital

    Ridgewood, New York, 07450

  • University of Rochester

    Rochester, New York, 14642

  • William Beaumont Hospital - Royal Oak

    Royal Oak, Michigan, 48073

  • Regional Cardiology Associates

    Sacramento, California, 95819

  • Kootenai Heart Clinics, LLC

    Spokane, Washington, 99204

  • Delta Heart and Medical Clinic

    Stockton, California, 95210

  • Stony Brook University Medical Center,

    Stony Brook, New York, 11794

  • Cardiac Study Center

    Tacoma, Washington, 98405

  • Tallahassee Research Institute, Inc.

    Tallahassee, Florida, 32308

  • The Toledo Hospital/Northwest Ohio Cardiology Consultants

    Toledo, Ohio, 43615

  • University of Arizona

    Tucson, Arizona, 85724

  • Brigham and Women's Cardiovascular Associates

    Warwick, Rhode Island, 02886

  • Washington Electrophysiology/Cardiovascular Research Institute

    Washington D.C., District of Columbia, 20010

  • University of Massachusetts-Worchester

    Worcester, Massachusetts, 01655

  • Lankenau Institute for Medical Research

    Wynnewood, Pennsylvania, 19096

  • Michigan Heart

    Ypsilanti, Michigan, 48197

Other trials in United States

Canada7 sites

  • University of Calgary

    Calgary, Alberta, T2N 4Z6

  • Royal Alexandra Hospital

    Edmonton, Alberta, T5H 3V9

  • Queen's University

    Kingston, Ontario, K7L 2V7

  • Montreal Heart Institute

    Montreal, Quebec, H1T 1C8

  • McGill University Health Centre

    Montreal, Quebec, H3G1A4

  • IUCPQ

    Québec, G1V 4G5

  • CHUS (Sherbrooke University)

    Sherbrooke, Quebec, J1H5N4

Other trials in Canada

About this study

Official title: Late Sodium Current Blockade in High-Risk ICD Patients

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.

Read the 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/cardiac resynchronization therapy-D patients.

Being tested
Ranolazine
Keywords
Sudden Death, Ranolazine, Heart failure, Ventricular tachycardia, Ventricular fibrillation, Implantable cardioverter-defibrillator
Medical subject headings
Heart Failure, Death, Sudden, Tachycardia, Ventricular, Ventricular Fibrillation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RanolazineDrug

    Also called Ranexa

    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.

Study groups in NCT01215253
Study groupRoleWhat they receive
RanolazineActive comparatorAt 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.
Receives: Drug: Ranolazine
PlaceboPlacebo comparatorAt 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.
Receives: Drug: Ranolazine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 2 years of follow-up on average

Secondary outcomes (9)

  1. Number of Patients With VT or VF Requiring ICD Shock or Death

    Implantable cardioverter-defibrillator (ICD) shock for VT or VF or death, whichever occurs first.

    Measured: 2 years of follow-up on average

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

    Total number of recurrent ICD therapies requiring antitachycardia pacing (ATP) or shock will be analyzed, not just first event

    Measured: 2 years of follow-up on average

  3. Number of Patients With First Inappropriate ICD Shock

    Number of patients with first inappropriate ICD shock for other reasons than VT or VF

    Measured: 2 years of follow-up on average

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

    Number of patients with a composite endpoint of cardiovascular hospitalization or death, whichever occurred first.

    Measured: 2 years of follow-up on average

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

    Number of patients with a composite endpoint of heart failure hospitalization or death, whichever occurred first.

    Measured: 2 years of follow-up on average

  6. Death

    Death as a safety endpoint of the trial

    Measured: 2 years of follow-up on average

  7. Mean Meters Walked in 6 Minutes

    Exercise capacity measured by the 6-minute walk test

    Measured: 1 year of follow-up

  8. Quality of Life Measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ)

    The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a new, self-administered, 23-item questionnaire that quantifies physical limitations, symptoms, self-efficacy, social interference and quality of life. The scale ranges from 0-100 with lower scores indicating worse outcomes.

    Measured: 1 year follow-up

  9. Number of Recurrent Inappropriate ICD Shocks

    Number of recurrent inappropriate ICD shocks in all patients combined.

    Measured: 2 years of follow-up on average

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Oct 2010 (estimated)
  2. Study startSep 2011
  3. Primary completion28 Feb 2017
  4. Study completion28 Feb 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,012 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01215253
Sponsor's protocol ID
U01HL096607
Acronym
RAID
Status last verified
Jul 2018
First submitted
30 Sep 2010
Last updated
27 Aug 2018
Data monitoring committee
Yes
FDA-regulated drug
Yes
Individual data sharing
No: 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.

Publications

  • 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.

    PubMed 38032582

  • 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.

    PubMed 35738852

  • 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.

    PubMed 30071993

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ranolazine in people with Ischemic Cardiomyopathy and Nonischemic Cardiomyopathy, run by University of Rochester at 90 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 90 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With Ventricular Tachycardia (VT) or Ventricular Fibrillation (VF) or Death (time frame: 2 years of follow-up on average). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01215253, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2018.

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