The Effects of Ranolazine on Exercise Capacity in Patients With Heart Failure With Preserved Ejection Fraction (RAZE)
Heart Failure With Preserved Ejection Fraction
About this trial
This is an interventional treatment trial for Heart Failure With Preserved Ejection Fraction focused on measuring HFPEF, Heart Failure, HF w/ preserved EF, Preserved EF, Preserved Ejection Fraction, Diastolic Dysfunction
Eligibility Criteria
I. Inclusion Criteria
- Age > 18 years old
Diagnosis of Heart Failure (HF) with Preserved Ejection Fraction (PEF)
- Signs or symptoms of heart failure (breathlessness, pulmonary congestion, edema, fatigue), NYHA (New York Heart Association) Class II-III HF AND
- LVEF (Left Ventricular Ejection Fraction) > 45% AND
Evidence of elevated LV filling pressures
- E/e-prime (E/e') mitral ratio > 8. Mitral E/e' ratio has been proposed as a noninvasive measure of left ventricular filling pressure.
- Brain natiuretic peptide (BNP) > 80 pg/mL. BNP is biomarker of ventricular wall stress.
- Pulmonary Artery systolic pressure estimated at > 35 mm Hg on echocardiography
- Stable medical management for at least 1 month
II. Exclusion Criteria
- Inability to perform 6 minute walk (6MW) test or 6 minute walk distance > 550 meters at baseline
- Inability to perform the Naughton protocol exercise test, or an absolute contraindication to exercise testing
- Decompensated heart failure
- Clinically significant valvular disease or congenital cardiac defects
- Clinical diagnosis of Chronic obstructive pulmonary disease (COPD) or significant lung pathology
- Prior treatment with ranolazine
- Percutaneous coronary intervention within the past 6 months or planned intervention during the study period
- Acute coronary syndrome within the prior 2 months
- Presence of uncorrected perfusion defects on stress testing
- Presence of angina
- Any rhythm other than sinus
- Electrocardiogram measured QTc interval > 500 msec
- Clinically significant hepatic impairment (ALT/AST > 3x upper limit of normal)
- Participation in another investigational drug or device study within 1 month prior to screening
- Females of childbearing potential
- Current treatment with potent inhibitors of hepatic cytochrome P450 (CYP) enzyme complex pathways affecting drug metabolism (e.g. ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir)
- Current treatment with CYP3A and/or P-Glycoprotein (Pgp) inducers (e.g. rifampin, rifampicin, carbamazepine, St. John's wort)
- Any other conditions that in the opinion of the investigators are likely to prevent compliance with the study protocol or pose a safety concern if the subject participates in the study.
Sites / Locations
- University of California, San Diego
Arms of the Study
Arm 1
Arm 2
Active Comparator
Placebo Comparator
Ranolazine
Placebo
Patients with be given 500 mg by mouth twice a day for three days, and then the dose will be increased to 1000 mg by mouth twice daily thereafter. (patients who concurrently take moderate CYP3A inhibitors including diltiazem, verapamil, aprepitant, erythromycin, and fluconazole will continue to 500 mg by mouth twice a day for the entire dosing period)
Patients will be given 1 tab twice a day for 3 days, then increasing to 2 tabs twice a day thereafter (patients who concurrently take moderate CYP3A inhibitors, will be given 1 tab twice daily for the entire dosing period)