Treatment With Ranolazine in Microvascular Coronary Dysfunction (MCD): Impact on Angina Myocardial Ischemia (RWISE)
Microvascular Coronary Dysfunction (MCD)
About this trial
This is an interventional treatment trial for Microvascular Coronary Dysfunction (MCD) focused on measuring Microvascular Coronary Dysfunction (MCD)
Eligibility Criteria
Inclusion Criteria:
- 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).
Exclusion Criteria:
- 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.
Sites / Locations
- 127 S. San Vicente Blvd, Suite A9303
- University of Florida
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Ranolazine
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.
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.