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

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Denise Barnard, University of California, San Diego
ClinicalTrials.gov Identifier:
NCT01505179
First received: December 8, 2011
Last updated: January 11, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention
Heart Failure With Preserved Ejection Fraction
Drug: Ranolazine
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effects of Ranolazine on Exercise Capacity in Patients With Heart Failure With Preserved Ejection Fraction

Resource links provided by NLM:


Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • Change in Exercise Capacity from Baseline at 6 Weeks [ Time Frame: Baseline and 6 weeks ] [ Designated as safety issue: No ]
    The primary endpoint for this study is the change in exercise capacity measured primarily by a treadmill test, but also by a six minute walk and oxygen uptake under stress.


Secondary Outcome Measures:
  • Echocardiographic Changes from Baseline at 6 Weeks [ Time Frame: Baseline and 6 weeks ] [ Designated as safety issue: No ]
    In order to determine any change in cardiac function, echocardiograms will be performed at baseling and the termination of the study drug.

  • Change in Quality of Life [ Time Frame: Baseline, 6-weeks, 8-weeks ] [ Designated as safety issue: No ]
    Questionnaires will be administered to assess quality of life prior and post treatment. These questionnaires are the Minnesota Living with Heart Failure Questiannaire and the Kansas City Cardiomyopathy Questionnaire.


Estimated Enrollment: 40
Study Start Date: February 2011
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ranolazine
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)
Drug: Ranolazine
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)
Other Names:
  • Ranexa
  • Ranolazine
Placebo Comparator: Placebo
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)
Drug: Placebo
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)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01505179

Locations
United States, California
University of California, San Diego
San Diego, California, United States, 92037
Sponsors and Collaborators
University of California, San Diego
Gilead Sciences
Investigators
Principal Investigator: Denise D Barnard, MD University of California, San Diego
  More Information

No publications provided

Responsible Party: Denise Barnard, Clinical Professor of Medicine, University of California, San Diego
ClinicalTrials.gov Identifier: NCT01505179     History of Changes
Other Study ID Numbers: IN-US-259-0109, 110344
Study First Received: December 8, 2011
Last Updated: January 11, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Diego:
HFPEF
Heart Failure
HF w/ preserved EF
Preserved EF
Preserved Ejection Fraction
Diastolic Dysfunction

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Ranolazine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 20, 2014