The Clinical Trial of Tamibarotene for Patients With HFpEF (RELIEF Trial)

NCT07855692 | Not Yet Recruiting Phase 2

• 1 other identifier: CAMCR-029
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 4

Brief 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).

Conditions

HFpEF - Heart Failure With Preserved Ejection Fraction

Keywords

HFpEF

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in serum NT-proBNP

  Baseline, 4 weeks, 12 weeks, 16 weeks

Secondary Outcomes (6)

• Subjects Included in the Composite Endpoint of CV Death, Hospitalization Due to Heart Failure

  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.

  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

  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

  Baseline, 4 weeks, 12 weeks, 16 weeks

• Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score

  Baseline, 12 weeks

Other Outcomes (2)

• sST2、serum TIMP-1、serum Meflin

  Baseline, 4 weeks, 12 weeks, 16 weeks

• Grip strength

  Baseline, 4 weeks, 12 weeks, 16 weeks

Study Arms (2)

Tamibarotene

EXPERIMENTAL

Patients will be randomized 1:1 to either tamibarotene or placebo.

Drug: Tamibarotene

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Tamibarotene DRUG

Tamibarotene 4 mg is administered orally once daily after breakfast for 12 weeks.

Tamibarotene

Placebo DRUG

Placebo is administered orally once daily after breakfast for 12 weeks.

Placebo

Eligibility Criteria

• Age: 26 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.
• \. Patients with LVEF of 50% or more as determined by echocardiography at screening.
• \. 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).
• \. 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.
• \. 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
• \. Patients with eGFR of 30 mL/min/1.73 m² or more at screening.
• \. Patients with a BMI of less than 45 kg/m² at screening.
• \. 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.
• \. Patients who agree to comply with the applicable requirement(s) below:
• \) 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.
• \) 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.
• \. Patients who are at least 26 years of age at the time informed consent is obtained.
• \. Patients who have voluntarily provided written informed consent after receiving adequate information about the study.

You may not qualify if:

• \. 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.
• \. Patients with a history of myocardial infarction or unstable angina within 12 weeks prior to enrollment.
• \. 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.
• \. 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.
• \. Patients who have received mechanical circulatory support within 12 weeks prior to enrollment.
• \. Patients with a history of stroke or transient ischemic attack within 12 weeks prior to enrollment.
• \. 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).
• \. Patients with pulmonary diseases, including primary pulmonary hypertension, chronic thromboembolic pulmonary hypertension, COPD, or interstitial lung disease.
• \. Patients with hepatic impairment (AST 100 IU/L or more, or ALT 100 IU/L or more).
• \. Patients with LDL cholesterol 180 mg/dL or more, or TG (non-fasting)300 mg/dL or more at screening.
• \. Patients receiving maintenance dialysis or those considered likely to require initiation of dialysis within 1 year.
• \. Patients with type 1 diabetes mellitus.
• \. Patients with hemoglobin less than 9.0 g/dL at screening.
• \. Patients with malignant neoplasms.
• \. Patients whose life expectancy is anticipated to be less than 1 year.

Sponsors & Collaborators

• Nagoya University: lead

Study Sites (4)

Nagoya University

Nagoya, Aichi-ken, 4668560, Japan

Location

National Center for Geriatrics and Gerontology

Ōbu, Aichi-ken, 474-8511, Japan

Location

Mie University Hospital

Tsu, Mie-ken, 514-8507, Japan

Location

Juntendo University Hospital

Tokyo, 113-8431, Japan

Location

MeSH Terms

Interventions

tamibarotene

Study Officials

• Katsuhiro Kato, M.D. Ph.D.

  Nagoya University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katsuhiro Kato, M.D. Ph.D.

CONTACT

+81 52 744 2150; kato.katsuhiro.x2@f.mail.nagoya-u.ac.jp

RELIEF Trial Coordinating Office

CONTACT

+81 52 744 2942; relief-office@med.nagoya-u.ac.jp

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: Dr.

Study Record Dates

• First Submitted: September 28, 2026
• First Posted: October 2, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): August 31, 2029
• Last Updated: October 2, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share

Locations

JP (4)