Heart Failure With Preserved Ejection FractionRAZENCT01505179
The Effects of Ranolazine on Exercise Capacity in Patients With Heart Failure With Preserved Ejection Fraction
A study testing Ranolazine in people with Heart Failure With Preserved Ejection Fraction, run by University of California, San Diego at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction
- What is being tested?
- Ranolazine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2011to Jan 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Diego
San Diego, California, 92037
About this study
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.
Read the 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.
Currently, ranolazine carries FDA approval for the treatment of chronic angina only. We intend to study ranolazine in patients with HFPEF, in the absence of documented ischemia, to determine whether the drug's lusitropic properties can improve exercise capacity in HFPEF patients.
Previous trials of ranolazine in patients with chronic angina found that there was a dose-dependent relationship between improvements in exercise capacity and ranolazine. However, there did appear to be a plateau in which 1500 mg of ranolazine twice daily improved exercise capacity only slightly more than 1000 mg of ranolazine given twice daily. Additionally, there was a substantially higher rate of adverse events (mainly nausea, dizziness, and asthenia) with the higher dose. Given the desire to maximize benefit and minimize the risk of adverse events, ranolazine 1000 mg by mouth twice daily was chosen as the target dose.
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.
- Being tested
- Ranolazine, Placebo
- Keywords
- HFPEF, Heart Failure, HF w/ preserved EF, Preserved EF, Preserved Ejection Fraction, Diastolic Dysfunction
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RanolazineDrug
Also called Ranexa
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)
PlaceboDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 6 weeks
Secondary outcomes (2)
Change in Quality of Life (QOL) Score
The Minnesota Living with Heart Failure (HF) Questionnaire was re-administered at the 6 week time point. The total quality of life (QOL) scores were compared to the baseline score. The well-validated Minnesota Living with Heart Failure questionnaire is self-administered, has 21 questions and takes 5-10 minutes to complete. The test measures perceived health-related QOL. Each question is scored from 0 to 5 on the Likert scale, where 0 is 'none', and 5 is 'very much'. QOL scores range from 0 to 105; a lower score represents a better quality of life. After an intervention, a decrease in score reflects an improvement in QOL. A minimally important difference in the total score is 5 points.
Measured: 6 weeks
Change in Doppler Echocardiographic Parameters, Septal E/e' Ratio (E/e')
Doppler echo allows non-invasive evaluation of diastolic cardiac function. The mitral inflow velocity (E) correlates with LV filling pressure, but is influenced by myocardial relaxation time (RT) and filling pressure. The early diastolic septal mitral annular tissue velocity (e') varies with RT alone. The unitless ratio of the E to e' velocities (E/e') is considered a reliable surrogate of LV filling pressure. Prediction of normal diastolic filling pressure is most reliable when E/e' is < 8; and of abnormal filling pressure when E/e' is > 15. The percent change is reported.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2012 (estimated)
- Study startFeb 2011
- Primary completionDec 2014
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heart Failure With Preserved Ejection FractionStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences
- Responsible party
- Principal investigator, Denise Barnard, University of California, San Diego
- Investigators
- Denise D Barnard, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01505179
- Sponsor's protocol ID
- IN-US-259-0109
- Other IDs
- 110344
- Acronym
- RAZE
- Status last verified
- Jan 2020
- First submitted
- 8 Dec 2011
- Last updated
- 18 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Ranolazine on Exercise Capacity in Patients With Heart Failure With Preserved Ejection Fraction
- ClinicalTrials.gov ID
- NCT01505179
- Acronym / sponsor ID
- RAZE / IN-US-259-0109
- Keywords
- HFPEF, Heart Failure, HF w/ preserved EF, Preserved EF, Preserved Ejection Fraction, Diastolic Dysfunction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- Gilead Sciences
- Study start
- Feb 2011
- Primary completion
- Dec 2014 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 6 Jan 2012 (estimated)
- Results
- Posted 18 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Currently, ranolazine carries FDA approval for the treatment of chronic angina only. We intend to study ranolazine in patients with HFPEF, in the absence of documented ischemia, to determine whether the drug's lusitropic properties can improve exercise capacity in HFPEF patients.
Previous trials of ranolazine in patients with chronic angina found that there was a dose-dependent relationship between improvements in exercise capacity and ranolazine. However, there did appear to be a plateau in which 1500 mg of ranolazine twice daily improved exercise capacity only slightly more than 1000 mg of ranolazine given twice daily. Additionally, there was a substantially higher rate of adverse events (mainly nausea, dizziness, and asthenia) with the higher dose. Given the desire to maximize benefit and minimize the risk of adverse events, ranolazine 1000 mg by mouth twice daily was chosen as the target dose.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ranolazine | Active comparator | Drug: RanolazinePatients 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) |
| Placebo | Placebo comparator | Drug: PlaceboPatients 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RanolazineAlso: RanexaPatients 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 |
| PlaceboPatients 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 |
Primary outcome
Change in Exercise Capacity at 6 Weeks
Time frame: 6 weeks
Exercise capacity in terms of exercise duration (time in seconds) as described for the baseline value, is repeated at 6 weeks.
Change in Oxygen Consumption (VO2) at 6 Weeks
Time frame: 6 weeks
Oxygen consumption (VO2) as described at baseline is remeasured after 6 weeks of drug vs placebo.
2 secondary outcomes
Change in Quality of Life (QOL) Score
Time frame: 6 weeks
Change in Doppler Echocardiographic Parameters, Septal E/e' Ratio (E/e')
Time frame: 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Denise D Barnard, MD principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ranolazine in people with Heart Failure With Preserved Ejection Fraction, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Exercise Capacity at 6 Weeks (time frame: 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2020.