Ranolazine Mediated PVC Reduction in Ischemic Heart Disease

• Status: Completed
• Trial end date: 2018-02-23
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine whether ranolazine has beneficial effects on cardiac ischemia through reduction of premature ventricular contraction burden.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kent Hospital, Rhode Island
• Collaborator: Gilead Sciences
• Treatments: Ranolazine

Criteria

Inclusion Criteria:

• Males and females aged 18 years and older

• Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures

• History of ischemic heart disease (prior bypass or coronary stenting, documentation on cardiac catheterization, nuclear SPECT imaging, cardiac MR, stress echocardiography, or exercise stress testing). Subjects are not required to have chronic angina to be enrolled in the study

• Elevated PVC burden (1%) on prior Holter/event monitor in previous 12 months or evidence for PVC(s) on baseline ECG within prior 12 months.

• Sexually active females of childbearing potential must agree to utilize effective methods of contraception during heterosexual intercourse throughout the treatment period and for 14 days following discontinuation of the study medication

Exclusion Criteria:

• Hospitalization for hyperthyroidism, pericarditis, myocarditis, or pulmonary embolism within 4 weeks prior to screening

• Implantation of ICD or permanent pacemaker within 1 month of screening

• New York Heart Association (NYHA) Class III and IV heart failure or NYHA Class II heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic within 4 weeks prior to Screening.

• Myocardial infarction, unstable angina, or coronary artery bypass graft (CABG) surgery within three months prior to Screening or percutaneous coronary intervention (PCI) within 4 weeks prior to Screening

• Clinically significant valvular disease in the opinion of the Investigator

• Stroke within 1 months prior to Screening

• History of serious ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation) within 4 weeks prior to Screening

• Family history of long QT syndrome

• QTc ≥ 500 msec (Bazett) at Screening ECG if in sinus rhythm (SR). If in AF, evidence of QTc ≥ 500 msec (Bazett) within 4 weeks prior to Screening

• Prior heart transplant

• Cardiac ablation within 3 months prior to Screening, or planned ablation during the course of the study

• Need for concomitant treatment during the trial, with drugs or products that are strong inhibitors of CYP3A, or inducers of CYP3A. Such medications should be discontinued 5-half- lives prior to the Run-in period

• Use of grapefruit juice or Seville orange juice during the study

• Use of drugs that prolong the QT interval

• Previous use of ranolazine within 2 months prior to screening

• Prior use of ranolazine which was discontinued for safety or tolerability

• Use of dabigatran during the study

• Use of a greater than 1000 mg total daily dose of metformin during the study

• Hypokalemia (serum potassium < 3.5 mEq/L) at Screening that cannot be corrected to a level of potassium ≥ 3.5 mEq/L prior to randomization

• Moderate and severe hepatic impairment (ie, Child-Pugh Class B and C), abnormal liver function test defined as ALT, AST, or bilirubin > 2 x ULN at Screening

• Severe renal impairment defined as creatinine clearance ≤ 30 mL/min at Screening

• Females who are pregnant or are breastfeeding

• Exclusion of patients with Contraindications to use of RANEXA, including patients on CYP3A4 inducers/potent inhibitors, and patients with liver cirrhosis

• Exclusion of Patients with CrCl < 30 mL/min

• Limit dose of RANEXA to 500mg BID in patients on concurrent diltiazem/verapamil

• Limit concurrent simvastatin to 20 mg/day

• In the judgment of the Investigator, any clinically-significant ongoing medical condition that might jeopardize the subject's safety or interfere with the study, including participation in another clinical trial within the previous 30 days using a therapeutic modality which could have potential residual effects that might confound the results of this study

• Any technical issue (device related) which in the judgment of the investigator would disrupt adequate data collection or interpretation