Enavogliflozin for treating diastolic dysfunction in nonobstructive hypertrophic cardiomyopathy

ENavogliflozin DElivering Alleviation of Ventricular Diastolic Dysfunction in nonObstRuctive Hypertrophic CardioMyopathy: a Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled Study (ENDEAVOR-HCM)

This study is testing if the medication enavogliflozin can help people with nonobstructive hypertrophic cardiomyopathy feel better and improve their heart function compared to a placebo over 24 weeks.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 19 Years to 80 Years
• Sex: All
• Sponsor: Yonsei University (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Seoul)
• Trial ID: NCT06580717 on ClinicalTrials.gov

What this trial studies

This study investigates the effects of enavogliflozin, an SGLT2 inhibitor, on left ventricular diastolic function in patients with nonobstructive hypertrophic cardiomyopathy. It aims to compare the drug's efficacy against a placebo over a 24-week period, focusing on improvements in exercise capacity, symptoms, serum biomarkers, and arrhythmic burden. Participants will be randomly assigned to receive either enavogliflozin or a placebo, with their diastolic function assessed through echocardiography. The study addresses a gap in treatment options for this specific patient population.

Who should consider this trial

Good fit: Ideal candidates include adults aged 19 to 80 with nonobstructive hypertrophic cardiomyopathy and no significant dynamic left ventricular outflow tract obstruction.

Not a fit: Patients with obstructive hypertrophic cardiomyopathy or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve heart function and quality of life for patients with nonobstructive hypertrophic cardiomyopathy.

How similar studies have performed: Previous studies have shown that SGLT2 inhibitors can improve heart failure outcomes, suggesting potential for success in this novel application.

Eligibility criteria

Inclusion Criteria:

1. A patient who understands the research protocol and fills out a consent form
2. Adults over 19 years of age and under 80 years of age
3. Non-diabetic or type 2 diabetic patients (HbA1c 6.5-10.5%)
4. Patients with non-obstructive hypertrophic cardiomyopathy who do not show significant dynamic left ventricular outflow tract obstruction at rest or during Valsalva maneuver or exercise stress on echocardiography within 3 months of the screening visit.

   * Non-obstructive hypertrophic cardiomyopathy: corresponds to maximum left ventricular outflow tract pressure gradient \<30mmHg.
   * Maximum left ventricular wall thickness ≥15mm if there is no family history of hypertrophic cardiomyopathy, or maximum left ventricular wall thickness ≥13mm if there is a family history of hypertrophic cardiomyopathy or positive for related genetic mutation.
5. For hypertrophic cardiomyopathy, existing beta blockers, calcium channel blockers, diuretics and Renin-angiotension-system(RAS) blockers (beta-blocker, non-dihydropyridine Calcium Cannel Blocker, loop diuretics, thiazide and thiazide-like diuretics, mineralocorticoid receptor antagonist, angiotensin converting enzyme inhibitor/angiotensin) For patients using receptor blocker/angiotensin receptor neprilysin inhibitor), the drug dose was stable for 2 weeks before screening and no change in dose is expected throughout the study period.
6. Women of childbearing age who agree to use contraception (hormones, intrauterine device, tubal ligation, spouse's vasectomy, etc.) for 30 days from the time of screening, during the clinical trial period, and after taking the clinical trial drug.
7. New York Heart Association (NYHA) Class 1\~3

Exclusion Criteria:

1. History of hypersensitivity to clinical trial drugs
2. If you are currently taking Sodium-glucose transporter 2 (SGLT2) inhibitors or within 4 weeks

   \- For diabetic patients, any type of hypoglycemic agent other than Sodium-glucose transporter 2 (SGLT2) inhibitors can be used.
3. Patients who cannot undergo diastolic stress echocardiography
4. Patients on dialysis or with chronic renal failure with an estimated glomerular filtration rate \<30 mL/min/1.73m2
5. Patients with Cardiac implantable electronic device (CIED)
6. Currently pregnant or lactating
7. ASpartate Transaminase(AST) or ALanine Transaminase(ALT) value more than 3 times the upper limit of normal during liver function test, history of hepatic coma, history of esophageal varices, history of porto-caval anastomosis.
8. Uncontrolled hypertension (SBP≥180mmHg or DBP≥110mmHg) or severe hypotension (SBP\<90mmHg)
9. Severe aortic or mitral stenosis with the possibility of surgery during the clinical trial period
10. Those waiting for a heart transplant or those who have received a heart transplant
11. Persons with diseases that need to be differentiated from heart failure symptoms at the investigator's discretion, such as severe anemia (hemoglobin \<7 g/dL), uncontrolled arrhythmia, severe lung disease, etc.
12. If you have cancer undergoing chemotherapy/radiation/surgical treatment or if your life expectancy is expected to be less than 1 year.
13. Untreated alcohol or drug abuse
14. If you are participating in the administration of another clinical trial drug or clinical trial device test, or have completed participation for less than 30 days.
15. Patients with type 1 diabetes or diabetic ketoacidosis
16. New York Heart Association (NYHA) class 4

Where this trial is running

Seoul

• Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine — Seoul, South Korea (Recruiting)

Study contacts

• Principal investigator: Jiwon Seo, MD — Gangnam Severance Hospital

Conditions Nonobstructive Hypertrophic Cardiomyopathy; non-obstructive; SGLT2; hypertrophic cardiomyopathy; HCM; ENDEAVOR-HCM; ertugliflozin