|Summary of Trial: |
The purpose of this study is to determine whether Ranolazine will decrease the likelihood of a composite arrhythmia endpoint consisting of ventricular tachycardia or ventricular fibrillation (VT/VF) requiring ATP therapy, ICD shocks, or death. This trial a randomized, double-blind placebo-controlled 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.
The study population will consist of patients with ischemic or nonischemic cardiomyopathy who receive their ICDs as standard of care for primary or secondary prevention of mortality following approved indications for ICD therapy. There are limited treatment options for patients at high risk of ventricular arrhythmic events. Ranolazine is a 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.
will be followed for a minimum of two years.
Since the study will enroll and subsequently randomize patients who are routinely implanted with ICD devices, exclusion criteria will be limited mostly to conditions precluding or limiting implantation of devices based on currently approved indications. We will exclude patients, who at the time of consent require therapy with amiodarone, sotalol or other antiarrhythmic drug. In cases of prior long-term use of these therapies, a period of a 3-month washout will be required for patients on amiodarone and a 1-week washout in patients on sotalol or other short-acting antiarrhythmic drug. For patients who have received short-term (up to 1 week) amiodarone therapy, there must be a 1 week wash-out period, prior to randomization to study drug.
|Principal Investigator:||Dr. Ronald Berger|
Kathy Avara, Research Coordinator
|Study Long Title: |
Ranolazine ICD Trial
|Study Short Title: ||RAID|
|JHU IRB Number:|
|Funding Source:||National Institute of Health|
- Secondary or primary prevention patients with ischemic or nonischemic cardiomyopathy who meet current guidelines for ICD or CRT-D device therapy and meet the above definition of high-risk patients
- Patient on stable optimal pharmacologic therapy for the cardiac condition
- Patient greater than or equal to 21 years of age without upper limit
- 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 on inotropic support
- Patient receiving amiodarone therapy at the time of consent (3-month washout is required if amiodarone was used after chronic administration; 1-week washout after short (≤1 week) intravenous or oral administration).
- Patients receiving any antiarrhythmic drug at the time of consent (1-week washout is required if sotalol was used)
- Patients receiving prophylactic ablation of ventricular substrate
- Patients with preexisting QTc prolongation >550ms
- Patients on agents known to prolong the QT interval
- 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, rifapentin, phenobarbital, phenytoin, carbamezepine 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
- 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
|Sponsor:||University of Rochester|
|Clinical Trial Site: |
Johns Hopkins Hospital
1800 Orleans Street
Sheikh Zayed Tower
Baltimore, MD 21287
|Anticipated End Date: ||2009|
|Compensation for Participating: ||None|