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Does Ranolazine Decrease Biomarkers of Myocardial Damage in Diabetics

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ClinicalTrials.gov Identifier: NCT02611596
Recruitment Status : Withdrawn
First Posted : November 23, 2015
Last Update Posted : May 17, 2017
Sponsor:
Information provided by (Responsible Party):
Todd C. Villines, 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.

Condition or disease Intervention/treatment Phase
Silent Myocardial Ischemia Type 2 Diabetes Drug: Ranolazine Drug: Placebo Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Other
Official Title: Does Ranolazine Decrease Biomarkers That Indicate Evidence of Myocardial Damage in Diabetics With Stable Ischemic Heart Disease? A Double-blinded, Randomized, Placebo Controlled Trial
Study Start Date : November 2016
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : November 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Ranolazine

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




Primary Outcome Measures :
  1. hs cTnT [ Time Frame: 24 weeks ]
    Does ranolazine decrease hs cTnT in subjects at high risk for silent myocardial ischemia?

  2. NT-pro-BNP [ Time Frame: 24 weeks ]
    Does ranolazine decrease NT-pro-BNP in subjects at high risk for silent myocardial ischemia?

  3. hsCRP [ Time Frame: 24 weeks ]
    Determine the degree of decrease of hs CRP in subjects in the ranolazine group.


Secondary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   30 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02611596


Sponsors and Collaborators
Walter Reed National Military Medical Center
Investigators
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Principal Investigator: Todd C Villines, MD WRNMMC

Publications:
Gilead Sciences, Inc. Ranolazine Investigator's Brochure. Section 3.2.2 Placebo Tablets, 30 Mar 2012.
FDA drug label for Ranolazine (Ranexa). Accessed via FDA website on 05 October 2012. Last revision Dec 2011. Reference ID: 3164047.

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Responsible Party: Todd C. Villines, MD, Walter Reed National Military Medical Center
ClinicalTrials.gov Identifier: NCT02611596     History of Changes
Other Study ID Numbers: 409189
First Posted: November 23, 2015    Key Record Dates
Last Update Posted: May 17, 2017
Last Verified: May 2017

Additional relevant MeSH terms:
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Myocardial Ischemia
Coronary Artery Disease
Ischemia
Pathologic Processes
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Coronary Disease
Arteriosclerosis
Arterial Occlusive Diseases
Ranolazine
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action