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Treatment With Ranolazine in Microvascular Coronary Dysfunction (MCD): Impact on Angina Myocardial Ischemia (RWISE)

This study has been completed.
Sponsor:
Collaborator:
University of Florida
Information provided by (Responsible Party):
Noel Bairey Merz, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier:
NCT01342029
First received: April 22, 2011
Last updated: October 18, 2016
Last verified: October 2016
  Purpose
This research study is designed to test the use of ranolazine in patients with angina (chest discomfort due to reduced blood supply to the heart) due to microvascular coronary dysfunction (MCD; abnormalities in the small blood vessels of the heart). This drug is approved by the U.S. Food and Drug Administration (FDA) for treatment of chronic angina. The FDA has approved this drug based on studies primarily on patients with chronic angina with major blockages of the arteries.

Condition Intervention
Microvascular Coronary Dysfunction (MCD)
Drug: Ranolazine
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Treatment With Ranolazine in Microvascular Coronary Dysfunction (MCD): Impact on Angina Myocardial Ischemia

Resource links provided by NLM:


Further study details as provided by Cedars-Sinai Medical Center:

Primary Outcome Measures:
  • 1a. Angina stability domain of the SAQ [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • 1b. Angina frequency domain of the SAQ [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • 1c. SAQ-7 [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 2. Angina frequency measured by diary [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • 3a. CMRI perfusion and diastolic function, Quality of Life (SF-36, DASI), Healthcare costs, Hemoglobin A1C, HOMA and BNP [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • 3b. Additional Aim: To determine if improvement in the SAQ is positively related to improvement in CMRI myocardial ischemia in subjects with signs and symptoms of ischemia but no obstructive CAD. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • 4. To determine in a randomized, double-blinded, placebo-controlled, cross-over trial of 2- weeks of ranolazine 500-1,000 mg po bid compared to placebo in subset of subjects on the exploratory outcome of physical activity measured by Fitbit. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Enrollment: 101
Study Start Date: May 2011
Study Completion Date: June 2016
Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ranolazine
147 subjects, with projected 9-10% dropout and anticipated 134 completed subjects will undergo baseline testing and then be randomized into a clinical cross-over trial of stepped dosing of ranolazine or placebo 500-1,000 mg po bid for 2 weeks with exit testing followed by cross-over to the alternate ranolazine or placebo and repeat exit testing.
Drug: Ranolazine

This drug is approved by the U.S. Food and Drug Administration (FDA) for treatment of chronic angina.

500-1,000 mg po bid for 2 weeks

Other Name: Ranexa
Placebo Comparator: Placebo
147 subjects, with projected 9-10% dropout and anticipated 134 completed subjects will undergo baseline testing and then be randomized into a clinical cross-over trial of stepped dosing of ranolazine or placebo 500-1,000 mg po bid for 2 weeks with exit testing followed by cross-over to the alternate ranolazine or placebo and repeat exit testing.
Drug: Placebo
500-1,000 mg po bid for 2 weeks

Detailed Description:

This is a randomized, double-blinded, placebo- controlled, and cross-over clinical trial. 147 subjects will be enrolled at two clinical sites, with projected 9-10% dropout and anticipated 134 completed subjects. To maintain blinding of the investigators, the study randomization table will be kept in Pharmacy Service. The sponsor will ship the study drug directly to the Pharmacy Service. The pharmacy service will also be responsible for dispersing the study drug.

There are 4 study visits (2 visits in each study period) in this study. Subjects will be in this study for about 6 weeks from Week 0 - baseline visit to Week 6 - exit visit. Besides the procedure of study medication mentioned above, other study procedures include informed consent, physical exam, questionnaires, EKG for safety assessment, blood collection for laboratory testing, cardiac MRI, and follow-up events. In sum, participants will be asked to undergo 2 cardiac MRI's and fill out questionnaires 4 times. They will be asked to participate for 6 weeks with two 2-week courses (with a treatment window period of 5 days), one with ranolazine and the other with placebo (without knowing which they are taking). There is a 2-week washout period between treatments. The participants will otherwise remain on all their usual medications. The physicians will also be blinded to which medication the subject is receiving.

Participation in this study will be approximately 6 weeks, which consists of two 2-week study periods and in between a 2-week washout period:

  1. During the first 2-week period: Subjects will be randomized to first receive either the ranolazine or a placebo pill (sugar pill with no active medicine). Subjects will take the extended-release ranolazine or a placebo pill for a total of 2 weeks. Subjects will take 500 mg twice daily for the first 1 week and then 1000 mg twice daily for an additional 1 week. Subjects who are unable to take the higher dose due to side effects will remain on 500 mg twice daily for the entire study period. After the 2 weeks, the participant will have a Cardiac MRI and complete study questionnaires. These tools will allow us to evaluate if the participant is doing better on the medication.
  2. 2-week washout period: Subject will then be asked to go 2 weeks without any study medication (ranolazine or placebo).
  3. During the second 2-week period: Subject will then be given either extended release ranolazine or placebo depending on which was received the first time for a total of 2 weeks. Subjects will take 500 mg twice daily for the first 1 week and then 1000 mg twice daily for an additional 1 week. Subjects who are unable to take the higher dose due to side effects will remain on 500 mg twice daily for entire study period. This 2-week period will again be followed by a final Cardiac MRI and questionnaire completion.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men or women age >18 from diverse racial/ethnic groups;
  2. Competent to give informed consent;
  3. Patients with chronic angina or its equivalent;
  4. Coronary angiogram revealing MCD with no obstructive CAD (epicardial coronary stenosis <50% luminal diameter stenosis);
  5. Left ventricular ejection fraction > or = 45%;
  6. Objective evidence of ischemia by noninvasive methods such as exercise stress test, stress Echo, MRI, or SPECT;
  7. Patients with 10% myocardial ischemia by Cardiac magnetic resonance imaging (CMRI) myocardial perfusion reserve index ≤ 2.0 or abnormal coronary reactivity testing (CFR < 2.5, or ACH response of no dilation or constriction, determined by local site read).

Exclusion Criteria:

  1. Acute coronary syndrome (defined by WHO), cardiogenic shock or requiring inotropic or intra-aortic balloon support;
  2. Planned percutaneous coronary intervention or CABG or established obstructive CAD with ischemia eligible for revascularization, acute MI;
  3. Prior non-cardiac illness with an estimated life expectancy <4 years;
  4. Unable to give informed consent;
  5. Allergy or contra-indication to CMRI testing, including renal failure, claustrophobia, and asthma, uncontrolled moderate hypertension (sitting blood pressure >160/95mmHg with measurements recorded on at least 2 occasions), conditions likely to influence outcomes: Severe lung, creatinine >1.8 or CrCl ≤ 50ml/min) or hepatic disease;
  6. Surgically uncorrected significant congenital or valvular heart disease and other disease likely to be fatal or require frequent hospitalization within the next six months;
  7. Adherence or retention reasons;
  8. Unwilling to complete follow-up evaluation including repeat testing, documented obstructive hypertrophic cardiomyopathy;
  9. Aortic stenosis (valve area <1.5cm);
  10. LV dysfunction (ejection fraction ≤35%);
  11. History of significant cocaine or amphetamine abuse;
  12. Taking potent CYP3A4 inhibitors (ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir);
  13. Women who are pregnant.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01342029

Locations
United States, California
8631 W. 3rd St, MOT Suite 740E
Los Angeles, California, United States, 90048
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
Sponsors and Collaborators
Cedars-Sinai Medical Center
University of Florida
Investigators
Principal Investigator: C. Noel Bairey Merz, MD Cedars-Sinai Medical Center
  More Information

Responsible Party: Noel Bairey Merz, Director, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT01342029     History of Changes
Other Study ID Numbers: IN-US-259-0124 - RWISE 
Study First Received: April 22, 2011
Last Updated: October 18, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Cedars-Sinai Medical Center:
Microvascular Coronary Dysfunction (MCD)

Additional relevant MeSH terms:
Ischemia
Myocardial Ischemia
Coronary Artery Disease
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

ClinicalTrials.gov processed this record on December 02, 2016