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

NCT01342029 | Completed Results DMC

• 1 other identifier: IN-US-259-0124 - RWISE
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Microvascular Coronary Dysfunction (MCD)

Keywords

Microvascular Coronary Dysfunction (MCD)

Outcome Measures

Primary Outcomes (1)

• Seattle Angina Questionnaire (SAQ)

  Questionnaires will be completed (SAQ - Seattle Angina Questionnaire) at the end of each treatment period. The Seattle Angina Questionnaire (SAQ) is a self-administered, 19-item questionnaire, a cardiac disease-related quality-of-life measure. The SAQ is well validated and sensitive to clinical changes. It has five subscales: physical limitation, angina stability, angina frequency, treatment satisfaction, and quality of life. The possible range of scores for each of the five subscales is 0 to 100, with higher scores indicating better quality of life. A change of 10 points in any of the subscales is considered to be clinically important.

  2 weeks (first intervention) and 6 weeks (second intervention)

Secondary Outcomes (1)

• Cardiac Magnetic Resonance (CMRs)

  2 weeks (first intervention) and 6 weeks (second intervention)

Study Arms (2)

Ranolazine

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Ranolazine DRUG

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

Also known as: Ranexa

Ranolazine

Placebo DRUG

500-1,000 mg po bid for 2 weeks

Placebo

Eligibility Criteria

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

You may qualify if:

• Men or women age \>18 from diverse racial/ethnic groups;
• Competent to give informed consent;
• Patients with chronic angina or its equivalent;
• Coronary angiogram revealing MCD with no obstructive CAD (epicardial coronary stenosis \<50% luminal diameter stenosis);
• Left ventricular ejection fraction \> or = 45%;
• Objective evidence of ischemia by noninvasive methods such as exercise stress test, stress Echo, MRI, or SPECT;
• 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).

You may not qualify if:

• Acute coronary syndrome (defined by WHO), cardiogenic shock or requiring inotropic or intra-aortic balloon support;
• Planned percutaneous coronary intervention or CABG or established obstructive CAD with ischemia eligible for revascularization, acute MI;
• Prior non-cardiac illness with an estimated life expectancy \<4 years;
• Unable to give informed consent;
• 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;
• Surgically uncorrected significant congenital or valvular heart disease and other disease likely to be fatal or require frequent hospitalization within the next six months;
• Adherence or retention reasons;
• Unwilling to complete follow-up evaluation including repeat testing, documented obstructive hypertrophic cardiomyopathy;
• Aortic stenosis (valve area \<1.5cm);
• LV dysfunction (ejection fraction ≤35%);
• History of significant cocaine or amphetamine abuse;
• Taking potent CYP3A4 inhibitors (ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir);
• Women who are pregnant.

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• University of Florida: collaborator

Study Sites (2)

127 S. San Vicente Blvd, Suite A9303

Los Angeles, California, 90048, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Related Publications (3)

• Rambarat CA, Elgendy IY, Handberg EM, Bairey Merz CN, Wei J, Minissian MB, Nelson MD, Thomson LEJ, Berman DS, Shaw LJ, Cook-Wiens G, Pepine CJ. Late sodium channel blockade improves angina and myocardial perfusion in patients with severe coronary microvascular dysfunction: Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction ancillary study. Int J Cardiol. 2019 Feb 1;276:8-13. doi: 10.1016/j.ijcard.2018.09.081. Epub 2018 Sep 26.

  PMID: 30293664 DERIVED

• Birkeland K, Khandwalla RM, Kedan I, Shufelt CL, Mehta PK, Minissian MB, Wei J, Handberg EM, Thomson LE, Berman DS, Petersen JW, Anderson RD, Cook-Wiens G, Pepine CJ, Bairey Merz CN. Daily Activity Measured With Wearable Technology as a Novel Measurement of Treatment Effect in Patients With Coronary Microvascular Dysfunction: Substudy of a Randomized Controlled Crossover Trial. JMIR Res Protoc. 2017 Dec 20;6(12):e255. doi: 10.2196/resprot.8057.

  PMID: 29263019 DERIVED

• Bairey Merz CN, Handberg EM, Shufelt CL, Mehta PK, Minissian MB, Wei J, Thomson LE, Berman DS, Shaw LJ, Petersen JW, Brown GH, Anderson RD, Shuster JJ, Cook-Wiens G, Rogatko A, Pepine CJ. A randomized, placebo-controlled trial of late Na current inhibition (ranolazine) in coronary microvascular dysfunction (CMD): impact on angina and myocardial perfusion reserve. Eur Heart J. 2016 May 14;37(19):1504-13. doi: 10.1093/eurheartj/ehv647. Epub 2015 Nov 27.

  PMID: 26614823 DERIVED

MeSH Terms

Interventions

Ranolazine

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: C.Noel Bairey Merz, MD
• Organization: Cedars-Sinai Medical Center

merz@cshs.org

310-423-9680

Study Officials

• C. Noel Bairey Merz, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: April 22, 2011
• First Posted: April 26, 2011
• Study Start: May 1, 2011
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: April 24, 2019
• Results First Posted: December 12, 2017

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will share

Locations

US (2)