HFpEF - Heart Failure With Preserved Ejection FractionPhase 2RELIEFNCT07855692
The Clinical Trial of Tamibarotene for Patients With HFpEF (RELIEF Trial)
A Phase 2 study testing Tamibarotene in people with HFpEF - Heart Failure With Preserved Ejection Fraction, run by Nagoya University at 4 sites in Japan.
Trial summary
This study will evaluate the effect of 12 weeks of treatment with tamibarotene compared with placebo on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients with heart failure with preserved ejection fraction (HFpEF). Read more about this study
- Who is it for?
- Ages 26 years and older
- Conditions the study is for
- HFpEF - Heart Failure With Preserved Ejection Fraction
- What is being tested?
- Tamibarotene
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 4 sitesJapan
- Study dates
- 1 Oct 2026to 31 Aug 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 26 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Patients who have been diagnosed with heart failure at least 12 weeks prior to providing informed consent and are classified as NYHA Class II to IV at screening.
- 2. Patients with LVEF of 50% or more as determined by echocardiography at screening.
- 3. Patients with an NT-proBNP level of 300 pg/mL or more at screening (or 600 pg/mL or more for patients with atrial fibrillation at screening).
- 4. Patients have evidence of structural heart disease (left atrial enlargement and/or left ventricular hypertrophy) based on echocardiography at screening, or who have a history of hospitalization for heart failure within 12 months prior to providing informed consent.
- 5. Patients receiving any of the following medications whose dosage regimen has remained unchanged for at least 4 weeks prior to the initiation of investigational product administration:
- ・Diuretics,SGLT2 inhibitors, ARNIs, ARBs, ACE inhibitors, MRAs, beta-blockers, digitalis preparations, HCN channel blockers, Soluble guanylate cyclase stimulators
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- 6. Patients with eGFR of 30 mL/min/1.73 m² or more at screening.
- 7. Patients with a BMI of less than 45 kg/m² at screening.
- 8. Patients with a systolic blood pressure of 160 mmHg or less and a diastolic blood pressure of 100 mmHg or less at screening, whose antihypertensive medication regimen has remained unchanged for at least 4 weeks prior to the initiation of investigational product administration.
- 9. Patients who agree to comply with the applicable requirement(s) below:
- 1) For female patients of childbearing potential, willingness to use contraceptionii from 30 days before the initiation of investigational product administration until 2 years after the end of investigational product administration.
- 2) For male patients with partners of childbearing potential, willingness to use contraceptionii from the initiation of investigational product administration until 6 months after the end of investigational product administration, and to refrain from sperm donation during this period.
- 10. Patients who are at least 26 years of age at the time informed consent is obtained.
- 11. Patients who have voluntarily provided written informed consent after receiving adequate information about the study.
Who cannot join
- 1. Patients diagnosed with acute heart failure, atrial fibrillation, or atrial flutter with a resting heart rate greater than 110 bpm within 4 weeks prior to enrollment.
- 2. Patients with a history of myocardial infarction or unstable angina within 12 weeks prior to enrollment.
- 3. Patients with chronic heart failure attributable to cardiac amyloidosis, glycogen storage disease, hypertrophic cardiomyopathy, active myocarditis, mitochondrial cardiomyopathy, cardiac sarcoidosis, arrhythmogenic right ventricular cardiomyopathy, constrictive endocarditis, cardiac tamponade, untreated severe valvular heart disease, congenital heart disease, or other similar conditions.
- 4. Patients who have undergone PCI, CABG, valvuloplasty, valve replacement surgery, catheter ablation, implantation of an ICD, CRT, or any other cardiac surgery within 12 weeks prior to enrollment, or who are expected to require any of these procedures during the study period.
- 5. Patients who have received mechanical circulatory support within 12 weeks prior to enrollment.
- 6. Patients with a history of stroke or transient ischemic attack within 12 weeks prior to enrollment.
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- 7. Patients with evidence of increased bleeding tendency or coagulation abnormalities, including thromboembolic disorders or hemorrhagic disorders (except for patients whose condition is adequately controlled with anticoagulants, antiplatelet agents, or similar medications).
- 8. Patients with pulmonary diseases, including primary pulmonary hypertension, chronic thromboembolic pulmonary hypertension, COPD, or interstitial lung disease.
- 9. Patients with hepatic impairment (AST 100 IU/L or more, or ALT 100 IU/L or more).
- 10. Patients with LDL cholesterol 180 mg/dL or more, or TG (non-fasting)300 mg/dL or more at screening.
- 11. Patients receiving maintenance dialysis or those considered likely to require initiation of dialysis within 1 year.
- 12. Patients with type 1 diabetes mellitus.
- 13. Patients with hemoglobin less than 9.0 g/dL at screening.
- 14. Patients with malignant neoplasms.
- 15. Patients whose life expectancy is anticipated to be less than 1 year.
- 16. Patients currently receiving vitamin A preparations or regularly taking supplements containing vitamin A.
- 17. Patients with hypervitaminosis A.
- 18. Breastfeeding female patients (except those who agree to discontinue breastfeeding during the investigational product treatment period and for 6 months after the last dose of investigational product).
- 19. Pregnant female patients or female patients with a positive pregnancy test result (female patients of childbearing potential who have had menstruation within 12 months prior to enrollment must undergo pregnancy testing; female patients for whom the possibility of pregnancy cannot be excluded, including those with amenorrhea for more than 12 months due to reasons such as chemical menopause, must also undergo pregnancy testing).
- 20. Patients with a history of hypersensitivity or anaphylactic reaction to any component of the investigational product.
- 21. Patients who have participated in, or are currently participating in, a clinical trial (observational clinical researches are permitted) within 4 weeks prior to enrollment.
- 22. Patients whom the Principal Investigator or Sub-Investigator considers unsuitable for participation in this study.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Japan4 sites, 4 recruiting
- Recruiting
Nagoya University
Nagoya, Aichi-ken, 4668560
RELIEF Trial Coordinating Office, +81 52 744 2942, relief-office@med.nagoya-u.ac.jp
- Not yet recruiting
National Center for Geriatrics and Gerontology
Ōbu, Aichi-ken, 474-8511
Atsuya Shimizu, MD, PhD, +81 562-46-2311, ashimizu@ncgg.go.jp
- Not yet recruiting
Juntendo University Hospital
Tokyo, 113-8431
Matsue Yuya, MD, PhD, +81-3-3813-3111, y-matsue@juntendo.ac.jp
- Not yet recruiting
Mie University Hospital
Tsu, Mie-ken, 514-8507
Keishi Moriwaki, +81 59-232-1111, kmoriwaki@clin.medic.mie-u.ac.jp
About this study
Official title: A Multicenter, Randomized, Placebo-controlled, Double-blind Clinical Trial: The Exploratory Clinical Trial to Evaluate the Efficacy and Safety of Low-dose Tamibarotene on Improving NT-proBNP in Patients With Heart Failure With Preserved Ejection Fraction (RELIEF Trial)
This study will evaluate the effect of 12 weeks of treatment with tamibarotene compared with placebo on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients with heart failure with preserved ejection fraction (HFpEF).
Read the detailed description
This is a multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy of tamibarotene in patients with HFpEF. Participants will receive tamibarotene 4 mg or matching placebo once daily for 12 weeks, in addition to standard-of-care therapy, including appropriate treatment of comorbidities.
Eligible participants will be adults aged ≥26 years with HFpEF, defined by a left ventricular ejection fraction (LVEF) ≥50%, evidence of structural heart disease, and New York Heart Association (NYHA) functional class II-IV symptoms. Participants who meet all inclusion and exclusion criteria will be randomized in a 1:1 ratio to receive either tamibarotene 4 mg or placebo.
The study will evaluate the change in NT-proBNP from baseline following 12 weeks of treatment.
- Being tested
- Tamibarotene, Placebo
- Keywords
- HFpEF
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TamibaroteneDrug
Tamibarotene 4 mg is administered orally once daily after breakfast for 12 weeks.
PlaceboDrug
Placebo is administered orally once daily after breakfast for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Tamibarotene | Experimental | Patients will be randomized 1:1 to either tamibarotene or placebo. Receives: Drug: Tamibarotene |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in serum NT-proBNP
Measured: Baseline, 4 weeks, 12 weeks, 16 weeks
Secondary outcomes (6)
Subjects Included in the Composite Endpoint of CV Death, Hospitalization Due to Heart Failure
Measured: Up to 16 weeks
Change From Baseline in Echocardiography (ECHO) Parameters: Left Ventricular End (LVE) Diastolic Diameter, LVE Systolic Diameter, Septal End Diastolic Thickness, Posterior LV Wall End Diastolic Thickness, Left Atrial Dimension.
A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters.
Measured: Baseline, 4 weeks, 12 weeks, 16 weeks
Change From Baseline in Echocardiography Parameters: Left Atrial Volume (LAV), LAV Index, Left Ventricular Ejection Fraction, Left Ventricular Mass (LVM), LVM Index, Tricuspid Regurgitation Velocity
A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters.
Measured: Baseline, 4 weeks, 12 weeks, 16 weeks
Change From Baseline in Echocardiography Parameters: Ewave Velocity, A Wave Velocity, e' at Septal Mitral Annulus, e' at Lateral Mitral Annulus, Ratio of E to A Velocity, E/e' Ratio
A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters.
Measured: Baseline, 4 weeks, 12 weeks, 16 weeks
Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score
Measured: Baseline, 12 weeks
Percentage of Participants With New York Heart Association (NYHA) Class I, II, II or IV
The NYHA Functional Classification classifies patients' heart failure according to the severity of their symptoms.
Measured: Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2026
- Study start1 Oct 2026 (estimated)
- Primary completion31 May 2029 (estimated)
- Study completion31 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HFpEF - Heart Failure With Preserved Ejection FractionStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nagoya University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Katsuhiro Kato, Nagoya University
- Investigators
- Katsuhiro Kato, M.D. Ph.D., Principal investigator, Nagoya University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07855692
- Sponsor's protocol ID
- CAMCR-029
- Other IDs
- jRCT2041260144
- Acronym
- RELIEF
- Status last verified
- Oct 2026
- First submitted
- 28 Sep 2026
- Last updated
- 30 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: If the principal investigator, clinical trial office, main stakeholder conclude that secondary use of individual data obtained in this clinical trial is beneficial for additional analysis, the secondary use of data excluding personal information will be acceptable after publication of results.
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Placebo-controlled, Double-blind Clinical Trial: The Exploratory Clinical Trial to Evaluate the Efficacy and Safety of Low-dose Tamibarotene on Improving NT-proBNP in Patients With Heart Failure With Preserved Ejection Fraction (RELIEF Trial)
- ClinicalTrials.gov ID
- NCT07855692
- Acronym / sponsor ID
- RELIEF / CAMCR-029
- Keywords
- HFpEF
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Nagoya UniversityUniversity, hospital or other
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 31 May 2029 (estimated)
- Study completion
- 31 Aug 2029 (estimated)
- First posted
- 2 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the effect of 12 weeks of treatment with tamibarotene compared with placebo on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients with heart failure with preserved ejection fraction (HFpEF).
Detailed description
This is a multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy of tamibarotene in patients with HFpEF. Participants will receive tamibarotene 4 mg or matching placebo once daily for 12 weeks, in addition to standard-of-care therapy, including appropriate treatment of comorbidities.
Eligible participants will be adults aged ≥26 years with HFpEF, defined by a left ventricular ejection fraction (LVEF) ≥50%, evidence of structural heart disease, and New York Heart Association (NYHA) functional class II-IV symptoms. Participants who meet all inclusion and exclusion criteria will be randomized in a 1:1 ratio to receive either tamibarotene 4 mg or placebo.
The study will evaluate the change in NT-proBNP from baseline following 12 weeks of treatment.
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 |
|---|---|---|
| Tamibarotene | Experimental | Drug: TamibarotenePatients will be randomized 1:1 to either tamibarotene or placebo. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 26 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 1. Patients who have been diagnosed with heart failure at least 12 weeks prior to providing informed consent and are classified as NYHA Class II to IV at screening.
- 2. Patients with LVEF of 50% or more as determined by echocardiography at screening.
- 3. Patients with an NT-proBNP level of 300 pg/mL or more at screening (or 600 pg/mL or more for patients with atrial fibrillation at screening).
- 4. Patients have evidence of structural heart disease (left atrial enlargement and/or left ventricular hypertrophy) based on echocardiography at screening, or who have a history of hospitalization for heart failure within 12 months prior to providing informed consent.
- 5. Patients receiving any of the following medications whose dosage regimen has remained unchanged for at least 4 weeks prior to the initiation of investigational product administration:
Key exclusion criteria (22 listed)
- 1. Patients diagnosed with acute heart failure, atrial fibrillation, or atrial flutter with a resting heart rate greater than 110 bpm within 4 weeks prior to enrollment.
- 2. Patients with a history of myocardial infarction or unstable angina within 12 weeks prior to enrollment.
- 3. Patients with chronic heart failure attributable to cardiac amyloidosis, glycogen storage disease, hypertrophic cardiomyopathy, active myocarditis, mitochondrial cardiomyopathy, cardiac sarcoidosis, arrhythmogenic right ventricular cardiomyopathy, constrictive endocarditis, cardiac tamponade, untreated severe valvular heart disease, congenital heart disease, or other similar conditions.
- 4. Patients who have undergone PCI, CABG, valvuloplasty, valve replacement surgery, catheter ablation, implantation of an ICD, CRT, or any other cardiac surgery within 12 weeks prior to enrollment, or who are expected to require any of these procedures during the study period.
- 5. Patients who have received mechanical circulatory support within 12 weeks prior to enrollment.
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 |
|---|---|---|
| TamibaroteneTamibarotene 4 mg is administered orally once daily after breakfast for 12 weeks. | Drug | Tamibarotene |
| PlaceboPlacebo is administered orally once daily after breakfast for 12 weeks. | Drug | Placebo |
Primary outcome
Change From Baseline in serum NT-proBNP
Time frame: Baseline, 4 weeks, 12 weeks, 16 weeks
6 secondary outcomes
Subjects Included in the Composite Endpoint of CV Death, Hospitalization Due to Heart Failure
Time frame: Up to 16 weeks
Change From Baseline in Echocardiography (ECHO) Parameters: Left Ventricular End (LVE) Diastolic Diameter, LVE Systolic Diameter, Septal End Diastolic Thickness, Posterior LV Wall End Diastolic Thickness, Left Atrial Dimension.
Time frame: Baseline, 4 weeks, 12 weeks, 16 weeks
Change From Baseline in Echocardiography Parameters: Left Atrial Volume (LAV), LAV Index, Left Ventricular Ejection Fraction, Left Ventricular Mass (LVM), LVM Index, Tricuspid Regurgitation Velocity
Time frame: Baseline, 4 weeks, 12 weeks, 16 weeks
Change From Baseline in Echocardiography Parameters: Ewave Velocity, A Wave Velocity, e' at Septal Mitral Annulus, e' at Lateral Mitral Annulus, Ratio of E to A Velocity, E/e' Ratio
Time frame: Baseline, 4 weeks, 12 weeks, 16 weeks
Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score
Time frame: Baseline, 12 weeks
Percentage of Participants With New York Heart Association (NYHA) Class I, II, II or IV
Time frame: Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2026.
- Individual participant dataSharing planned: Yes. If the principal investigator, clinical trial office, main stakeholder conclude that secondary use of individual data obtained in this clinical trial is beneficial for additional analysis, the secondary use of data excluding personal information will be acceptable after publication of results.
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Descriptive Study of Circulating Gene or Protein Inflammatory Biomarkers and Bioimpedance Parameters in a Population of Patients Hospitalized for Decompensated Heart Failure With Preserved or Mildly Reduced Cardiac Function
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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.
Katsuhiro Kato, M.D. Ph.D. principal investigator
Nagoya University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tamibarotene in people with HFpEF - Heart Failure With Preserved Ejection Fraction, run by Nagoya University at 4 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 22 exclusion criteria. 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: looking for participants now, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Japan. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Katsuhiro Kato, M.D. Ph.D. (+81 52 744 2150, kato.katsuhiro.x2@f.mail.nagoya-u.ac.jp), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in serum NT-proBNP (time frame: Baseline, 4 weeks, 12 weeks, 16 weeks). 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 30 Oct 2026.