Does Ranolazine Decrease Biomarkers of Myocardial Damage in Diabetics

NCT02611596 | Withdrawn

• 1 other identifier: 409189
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (3)

• hs cTnT

  Does ranolazine decrease hs cTnT in subjects at high risk for silent myocardial ischemia?

  24 weeks

• NT-pro-BNP

  Does ranolazine decrease NT-pro-BNP in subjects at high risk for silent myocardial ischemia?

  24 weeks

• hsCRP

  Determine the degree of decrease of hs CRP in subjects in the ranolazine group.

  24 weeks

Secondary Outcomes (1)

• prevalence of hs cTnT > 99th percentile

  24 weeks

Study Arms (2)

Ranolazine

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Ranolazine DRUG

24 weeks of the assigned medication

Ranolazine

Placebo DRUG

Placebo for 24 weeks

Placebo

Eligibility Criteria

• Age: 30 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Walter Reed National Military Medical Center: lead

Related Publications (22)

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• Gilead Sciences, Inc. Ranolazine Investigator's Brochure. Section 3.2.2 Placebo Tablets, 30 Mar 2012.

  BACKGROUND

• FDA drug label for Ranolazine (Ranexa). Accessed via FDA website on 05 October 2012. Last revision Dec 2011. Reference ID: 3164047.

  BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Ranolazine

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Todd C Villines, MD

  WRNMMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: November 18, 2015
• First Posted: November 23, 2015
• Study Start: November 1, 2016
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2019
• Last Updated: May 17, 2017

Record last verified: 2017-05