Does Ranolazine Decrease Biomarkers of Myocardial Damage in Diabetics

NCT ID: NCT02611596

Last Updated: 2017-05-17

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2019-11-30

Brief Summary

The purpose of this investigation is to compare subjects at high risk for silent myocardial ischemia in the placebo group to subjects at high risk for silent myocardial ischemia in the ranolazine group to determine if ranolazine can be used as a treatment to decrease silent myocardial ischemia (SMI). Subjects at high risk for silent myocardial ischemia are defined in this protocol as diabetics with stable ischemic heart disease. This study will look at the impact ranolazine treatment has on biomarkers that have been shown to be highly associated with increased risk of morbidity and mortality in relation to SMI. If the hypothesis is correct, further studies can be conducted to determine if treatment with ranolazine has impact on long-term outcomes such as hospitalizations, myocardial infarction, congestive heart failure or sudden cardiac death.

Conditions

Silent Myocardial Ischemia; Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Ranolazine

Subjects will take one 500mg tablet twice daily (500mg BID) for seven days and then increase to two 500mg tablets twice daily (1000mg BID) for the remainder of the study, for a total of 24 weeks. Subjects taking moderate CYP3A4 inhibitors will not participate in upward titration and will remain on 500mg tablet twice daily (500mg BID) for the duration of the trial.

Group Type: EXPERIMENTAL

Ranolazine

Intervention Type: DRUG

24 weeks of the assigned medication

Placebo

Subjects will take one placebo tablet (identical to the 500mg Ranolazine tablet) twice daily (500mg BID) for seven days and then increase to two 500mg tablets twice daily (1000mg BID) for the remainder of the study, for a total of 24 weeks. Subjects taking moderate CYP3A4 inhibitors will not participate in upward titration and will remain on 500mg tablet twice daily (500mg BID) for the duration of the trial.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo for 24 weeks

Interventions

Ranolazine

24 weeks of the assigned medication

Intervention Type: DRUG

Placebo

Placebo for 24 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjects at risk for silent myocardial ischemia as defined by:
• Stable ischemic heart disease as defined by:

• Obstruction of at least one epicardial vessel of > 50 percent by invasive or non-invasive coronary angiography, or
• Evidence of ischemia or infarct on SPECT imaging, or
• History of myocardial infarction > 3 months ago, or
• Stent placement (PCI) > 3 months ago, or
• Coronary artery bypass grafting (CABG) > 3 months ago AND
• Type 2 diabetics as defined by:

• HgbA1C ≥ 6.5 percent, or
• Fasting Blood Glucose > 125 mg/dL on two or more blood draws, or
• Random Blood Glucose of ≥ 200 mg/dL on a single blood draw, or
• Previous diagnosis of type 2 diabetes listed in the subject's medical record AND

• On Optimal Medical Therapy as defined as being on ALL of the following at time of enrollment:
• Beta Blocker
• Aspirin
• Statin AND
• Females < 60 who have not been free of menstruation for 2 years (menopause diagnosed) or who do not have documented history of hysterectomy must be willing to use at least one form of birth control (including abstinence as an option) for the duration of the study. If condoms are the method chosen, they are strongly urged to use a second form of birth control in addition to condoms.

AND

Screening Criteria met:

• hs cTnT > 0.014 ng/mL

Exclusion Criteria

• Percutaneous intervention/stent placement in the past 3 months
• Coronary artery bypass grafting in the past 3 months
• Treatment with ranolazine in the past 12 months
• Significant lung disease, COPD or use of supplemental oxygen
• Cirrhosis
• Estimated Glomerular Filtration Rate (GFR) < 30
• Subject taking strong CYP3A inhibitors (ketoconazole, itraconazole, clarithryomycin, nefazodone, nelfinavir, ritonavir, indinavir and saquinavir)
• Subject taking strong CYP3A inducers (rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine, St. John's wort)
• Subjects taking P-gp Inhibitors (cyclosporine)
• Subject is taking concurrent simvastatin in > 20 mg/day
• Subject is taking metformin > 1700 mg/day
• NYHA Class 3 or 4 Heart Failure (severe)
• Canadian Cardiovascular Society Grade 4 Angina
• Unstable angina defined as a new angina occurring after minimal exercise or at rest OR a significant increase in angina severity (≥ 2 CCS grades) occurring with minimal exertion, with high clinical suspicion of acute coronary syndrome.
• Planned PCI or Cardiac Surgery
• Pregnant females or females trying to become pregnant
• Breast-feeding females
• Subjects younger than age 30 or older than age 85
• Lactose Intolerance (placebo has lactose monohydrate)
• Lactose/Milk allergy (placebo has lactose monohydrate)
• QTc > 500 msec

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Walter Reed National Military Medical Center

FED

Sponsor Role: lead

Responsible Party

Todd C. Villines

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Todd C Villines, MD

Role: PRINCIPAL_INVESTIGATOR

WRNMMC

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Other Identifiers

409189

Identifier Type: -

Identifier Source: org_study_id