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

This study is currently recruiting participants. (see Contacts and Locations)
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
  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:
  • 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


Estimated Enrollment: 134
Study Start Date: May 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
Drug: Placebo
1,000 mg po bid for 2 weeks

Detailed Description:

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
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 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.
  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

Contacts
Contact: C. Noel Bairey Merz, MD 310-423-9680 merz@cshs.org
Contact: Puja Mehta, MD 310-423-9666 puja.mehta@cshs.org

Locations
United States, California
8631 W. 3rd St, MOT Suite 740E Recruiting
Los Angeles, California, United States, 90048
Contact: Ying Mou, PhD    310-248-7669    Ying.Mou@cshs.org   
Contact: Rosario Ando    310-423-9666    Rosario.Ando@cshs.org   
Principal Investigator: C. Noel Bairey Merz, MD         
Sub-Investigator: Puja Mehta, MD         
Sub-Investigator: Chrisandra Shufelt, MD         
Sub-Investigator: Louise Thomson, MD         
Sub-Investigator: Daniel Berman, MD         
Sub-Investigator: Debiao Li, MD         
Sub-Investigator: Piotr Slomka, PhD         
Sub-Investigator: Margo Minissian, NP         
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32610
Contact: Carl Pepine, MD    352-273-9082    Carl.Pepine@medicine.ufl.edu   
Contact: Kristi Cromwell-Cain    3522738945    kristi.cromwell-cain@medcine.ufl.edu   
Sub-Investigator: Eileen M Handberg, PhD         
Principal Investigator: Carl Pepine, MD         
Sponsors and Collaborators
Cedars-Sinai Medical Center
University of Florida
Investigators
Principal Investigator: C. Noel Bairey Merz, MD Cedars-Sinai Medical Center
  More Information

No publications provided

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: May 6, 2013
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Myocardial Ischemia
Coronary Artery Disease
Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Coronary Disease
Arteriosclerosis
Arterial Occlusive Diseases
Pathologic Processes
Ranolazine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014