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

NCT01505179 | Completed Results

• 2 other identifiers: IN-US-259-0109110344
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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, or HFPEF.

Conditions

Heart Failure With Preserved Ejection Fraction

Keywords

HFPEF; Heart Failure; HF w/ preserved EF; Preserved EF; Preserved Ejection Fraction; Diastolic Dysfunction

Outcome Measures

Primary Outcomes (2)

• Change in Exercise Capacity at 6 Weeks

  Exercise capacity in terms of exercise duration (time in seconds) as described for the baseline value, is repeated at 6 weeks.

  6 weeks

• Change in Oxygen Consumption (VO2) at 6 Weeks

  Oxygen consumption (VO2) as described at baseline is remeasured after 6 weeks of drug vs placebo.

  6 weeks

Secondary Outcomes (2)

• Change in Quality of Life (QOL) Score

  6 weeks

• Change in Doppler Echocardiographic Parameters, Septal E/e' Ratio (E/e')

  6 weeks

Study Arms (2)

Ranolazine

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Ranolazine DRUG

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)

Also known as: Ranexa

Ranolazine

Placebo DRUG

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)

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Diego: lead
• Gilead Sciences: collaborator

Study Sites (1)

University of California, San Diego

San Diego, California, 92037, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Ranolazine

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Due to slower than anticipated enrollment, only 10 subjects out of an intended 40 completed the study in the time allowed by the sponsor. The statistical analyses and inferences are restricted by low sample size and population baseline differences.

Results Point of Contact

• Title: Denise Barnard, MD
• Organization: UCSD MED CLINICAL TRIALS

dbarnard@ucsd.edu

858 246-2996

Study Officials

• Denise D Barnard, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor of Medicine

Study Record Dates

• First Submitted: December 8, 2011
• First Posted: January 6, 2012
• Study Start: February 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: January 1, 2015
• Last Updated: January 18, 2020
• Results First Posted: January 18, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)