Does Ranolazine Decrease Biomarkers of Myocardial Damage in Diabetics

Not Applicable

Withdrawn

• Conditions: Silent Myocardial Ischemia; Type 2 Diabetes
• Interventions: Drug: Placebo; Drug: Ranolazine

• Registration Number: NCT02611596
• Lead Sponsor: Walter Reed National Military Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-11-18
• Study First Submitted QC: 2015-11-20
• Study First Posted: 2015-11-23
• Study Start: 2016-11
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-16
• Last Update Posted: 2017-05-17
• Primary Completion: 2018-11
• Study Completion: 2019-11

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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.
Ranolazine	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.

Primary Outcome Measures

Name	Time	Method
hs cTnT	24 weeks	Does ranolazine decrease hs cTnT in subjects at high risk for silent myocardial ischemia?
NT-pro-BNP	24 weeks	Does ranolazine decrease NT-pro-BNP in subjects at high risk for silent myocardial ischemia?
hsCRP	24 weeks	Determine the degree of decrease of hs CRP in subjects in the ranolazine group.

Secondary Outcome Measures

Name	Time	Method
prevalence of hs cTnT > 99th percentile	24 weeks	Determine the prevalence of hs cTnT greater than the 99th percentile (0.014 ng/mL) in asymptomatic diabetic subjects with stable ischemic heart disease.