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

This study is currently recruiting participants.
Verified May 2013 by Cedars-Sinai Medical Center
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: May 6, 2013
Last verified: May 2013

April 22, 2011
May 6, 2013
May 2011
December 2015   (final data collection date for primary outcome measure)
Angina to be measured by diary for frequency of episodes and NTG use [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Angina will be measured by the "angina stability" domain of the SAQ in 134 subjects with signs and symptoms of ischemia but no obstructive CAD
Same as current
Complete list of historical versions of study NCT01342029 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Treatment With Ranolazine in Microvascular Coronary Dysfunction (MCD): Impact on Angina Myocardial Ischemia
Treatment With Ranolazine in Microvascular Coronary Dysfunction (MCD): Impact on Angina Myocardial Ischemia

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.

This is a randomized, double-blinded, placebo- controlled, and cross-over clinical trial. 134 subjects will be enrolled at two clinical sites with 67 subjects at Cedars-Sinai Medical Center. 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, 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.
Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Microvascular Coronary Dysfunction (MCD)
  • Drug: Ranolazine

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

    1,000 mg po bid for 2 weeks

    Other Name: Ranexa
  • Drug: Placebo
    1,000 mg po bid for 2 weeks
  • Experimental: ranolazine
    134 subjects will undergo baseline testing and then be randomized into a clinical cross-over trial of stepped dosing of ranolazine or placebo 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.
    Intervention: Drug: Ranolazine
  • Placebo Comparator: Placebo
    134 subjects will undergo baseline testing and then be randomized into a clinical cross-over trial of stepped dosing of ranolazine or placebo 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.
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
134
December 2015
December 2015   (final data collection date for primary outcome measure)

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 or SPECT;
  7. Patients with 10% myocardial ischemia by CMR perfusion.

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.
Both
18 Years and older
No
Contact: C. Noel Bairey Merz, MD 310-423-9680 merz@cshs.org
Contact: Puja Mehta, MD 310-423-9666 puja.mehta@cshs.org
United States
 
NCT01342029
IN-US-259-0124 - RWISE
Yes
Noel Bairey Merz, Cedars-Sinai Medical Center
Cedars-Sinai Medical Center
University of Florida
Principal Investigator: C. Noel Bairey Merz, MD Cedars-Sinai Medical Center
Cedars-Sinai Medical Center
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP