The Effects of Ranolazine on Exercise Capacity in Patients With Heart Failure With Preserved Ejection Fraction

Condition(s) targeted: Heart Failure With Preserved Ejection Fraction

Intervention: Ranolazine (Drug); Placebo (Drug)

Phase: N/A

Status: Enrolling by invitation

Sponsored by: University of California, San Diego

Official(s) and/or principal investigator(s):
Denise D Barnard, MD, Principal Investigator, Affiliation: University of California, San Diego

The purpose of this study is to determine whether treatment with Ranolazine will improve exercise capacity in patients with Heart Failure with preserved left ventricular ejection fraction.

Official title: The Effects of Ranolazine on Exercise Capacity in Patients With Heart Failure With Preserved Ejection Fraction

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Change in Exercise Capacity from Baseline at 6 Weeks

Secondary outcome:

Echocardiographic Changes from Baseline at 6 Weeks

Change in Quality of Life

Detailed description: Denise Barnard, M. D., and her associates, are conducting a research study to find out more about ways to improve symptoms in patients with Heart Failure with Preserved Ejection Fraction (HFPEF). Heart failure with preserved ejection fraction is a condition where the heart squeezes well but is stiff. This stiffness in the heart muscle makes the heart unable to fill, leading to shortness of breath and decreased exercise tolerance. Subjects with HFPEF are asked to participate in this study. There will be approximately 40 participants enrolled in this study. The purpose of this study is to investigate the effects of Ranolazine (Ranexa) in patients with HFPEF. The study is sponsored by the manufacturers of the drug, Gilead Pharmaceuticals. Ranolazine is a drug that affects the ion channels in the heart. In patients with heart failure, these ion channels do not work properly, and contribute to make the heart stiff. A stiff heart leads to the symptoms of shortness of breath which patients with HFPEF experience. Due to its properties, Ranolazine may improve this stiffness. Ranolazine could improve subject's shortness of breath and ability to exercise. Ranolazine is approved for patients who suffer from chest pain and has been shown to help these patients be able to exercise longer and have less chest pain. Ranolazine has not been approved for improvement in exercise in patients with HFPEF. The investigators hope to study whether Ranolazine can help patients with HFPEF in this study. To properly evaluate the effects of Ranolazine, this research study is set up as a double blind, placebo controlled study. Subjects will be randomly assigned (like rolling a dice) to either Ranolazine or placebo (inactive substance). Subjects will have a 50% chance of getting the study drug and 50% chance of getting placebo.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

I. Inclusion Criteria

- Age > 18 years old

- Diagnosis of HFPEF:

- Signs or symptoms of heart failure (breathlessness, pulmonary congestion, edema,

fatigue), NYHA Class II-III CHF AND

- LVEF > 45% AND

- Evidence of elevated LV filling pressures

1. E/E'mitral > 8 2. BNP > 80 pg/mL

- PA systolic pressure > 35 mm Hg on echocardiography

- Stable medical management for at least 1 month

II. Exclusion Criteria

- Inability to perform 6 minute walk 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 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

- QTc > 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 CYP3A (e. g. ketoconazole, itraconazole,

clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir)

- Current treatment with CYP3A and P-GP 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.

University of California, San Diego, San Diego, California 92037, United States

Starting date: February 2011
Last updated: January 11, 2013