Does Ranolazine Decrease Biomarkers of Myocardial Damage in Diabetics

May 16, 2017 updated by: Todd C. Villines, Walter Reed National Military Medical Center

Does Ranolazine Decrease Biomarkers That Indicate Evidence of Myocardial Damage in Diabetics With Stable Ischemic Heart Disease? A Double-blinded, Randomized, Placebo Controlled Trial

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 85 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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.
Drug: Ranolazine
24 weeks of the assigned medication
PLACEBO_COMPARATOR: 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.
Drug: Placebo
Placebo for 24 weeks

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
prevalence of hs cTnT > 99th percentile
Time Frame: 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.
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Walter Reed National Military Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2016

Primary Completion (ANTICIPATED)

November 1, 2018

Study Completion (ANTICIPATED)

November 1, 2019

Study Registration Dates

First Submitted

November 18, 2015

First Submitted That Met QC Criteria

November 20, 2015

First Posted (ESTIMATE)

November 23, 2015

Study Record Updates

Last Update Posted (ACTUAL)

May 17, 2017

Last Update Submitted That Met QC Criteria

May 16, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 409189

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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