Ranolazine Implantable Cardioverter-Defibrillator Trial
Condition: Ischemic Cardiomyopathy; Nonischemic Cardiomyopathy; Heart Failure
MeSH terms: Heart Failure; Cardiomyopathies
Intervention: Ranolazine
Intervention description: 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.
Intervention MeSH terms: Ranolazine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1012.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No
Keywords: Sudden Death; Ranolazine; Heart failure; Ventricular tachycardia; Ventricular fibrillation; Implantable cardioverter-defibrillator

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.
    

Eligibility 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