ENavogliflozin DElivering Alleviation of Ventricular Diastolic Dysfunction in nonObstRuctive Hypertrophic CardioMyopathy

NCT ID: NCT06580717

Last Updated: 2024-11-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-15
• Study Completion Date: 2026-11-30

Brief Summary

The primary objective of this study is to investigate the effect of enavogliflozin, an Sodium-glucose transporter 2 (SGLT2) inhibitor, compared with placebo on left ventricular diastolic function in patients with nonobstructive hypertrophic cardiomyopathy. The secondary objective of this study is to investigate the effect of enavogliflozin on exercise capacity, symptoms, serum biomarkers, and arrhythmic burden in patients with nonobstructive hypertrophic cardiomyopathy.

Detailed Description

Most of the medication used in HCM(hypertrophic cardiomyopathy) targets dynamic left ventricular obstruction and hypercontractility. Guidelines recommend that beta-blockers and calcum channels can also be used to lower heart rate and improve diastolic function in symptomatic nonobstructive HCM(hypertrophic cardiomyopathy), and that diuretics may be considered next, but there is a paucity of evidence supporting these recommendations. Left ventricular diastolic dysfunction is the main pathophysiological mechanism in nonobstructive HCM. SGLT2(Sodium-glucose transporter 2) inhibitors have been shown to reduce heart failure events and mortality in patients with heart failure with preserved ejection fraction, and have also been reported to improve left ventricular diastolic function. This study will investigate the efficacy and safety of enavogliflozin, an SGLT2(Sodium-glucose transporter 2) inhibitor, compared with placebo in patients with nonobstructive hypertrophic cardiomyopathy, over a period of 6 months.

Patients with hypertrophic cardiomyopathy and without evidence of dynamic left ventricular outflow tract obstruction at resting or on provocation by Valsalva maneuver or exercise will be enrolled. Participants will be randomly assigned to the enavogliflozin 0.3mg group and the placebo group in a 1:1 ratio and will continue the medication for 24 weeks. Changes in left ventricular diastolic reserve assessed by diastolic stress echocardiography will be compared between the treatment groups at 24 weeks. Changes in other parameters of diastolic function and exercise capacity will be assessed by diastolic stress echocardiography and compared between the treatment groups. Symptom status, serum biomarker levels, and arrhythmic burden on 24 hour ambulatory electrocardiogram will also be compared between the treatment groups. Post-trial follow-up will be performed at 52 weeks.

Conditions

Nonobstructive Hypertrophic Cardiomyopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Enavogliflozin 0.3mg

Patients who are eligible for all of the criteria and who do not qualify as exclusion criteria should be enrolled in the study and randomly enrolled in a 1: 1 dose of enavogliflozin 0.3 mg once daily or placebo.

Group Type: EXPERIMENTAL

enavogliflozin 0.3mg

Intervention Type: DRUG

Enavogliflozin 0.3mg, 1 tablet once a day, is prescribed for a period of 24 weeks.

Patients who are eligible for all of the criteria and who do not qualify as exclusion criteria should be enrolled in the study and randomly enrolled in a 1: 1 dose of enavogliflozin 0.3 mg once daily or placebo.

Enavogliflozin placebo

Patients who are eligible for all of the criteria and who do not qualify as exclusion criteria should be enrolled in the study and randomly enrolled in a 1: 1 dose of enavogliflozin 0.3 mg once daily or placebo.

Group Type: PLACEBO_COMPARATOR

enavogliflozin Placebo

Intervention Type: DRUG

A placebo pill identical to enavogliflozin, 1 tablet once a day, is prescribed for a period of 24 weeks.

Patients who are eligible for all of the criteria and who do not qualify as exclusion criteria should be enrolled in the study and randomly enrolled in a 1: 1 dose of enavogliflozin 0.3 mg once daily or placebo.

Interventions

enavogliflozin 0.3mg

Enavogliflozin 0.3mg, 1 tablet once a day, is prescribed for a period of 24 weeks.

Patients who are eligible for all of the criteria and who do not qualify as exclusion criteria should be enrolled in the study and randomly enrolled in a 1: 1 dose of enavogliflozin 0.3 mg once daily or placebo.

Intervention Type: DRUG

enavogliflozin Placebo

A placebo pill identical to enavogliflozin, 1 tablet once a day, is prescribed for a period of 24 weeks.

Patients who are eligible for all of the criteria and who do not qualify as exclusion criteria should be enrolled in the study and randomly enrolled in a 1: 1 dose of enavogliflozin 0.3 mg once daily or placebo.

Intervention Type: DRUG

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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yonsei University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jiwon Seo, MD

Role: PRINCIPAL_INVESTIGATOR

Gangnam Severance Hospital

Jang-Won Son, MD

Role: PRINCIPAL_INVESTIGATOR

Yeungnam University Hospital

In-Cheol Kim, MD

Role: PRINCIPAL_INVESTIGATOR

Keimyung University Dongsan Medical Center

Locations

Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine

Seoul, , South Korea

Site Status: RECRUITING

Countries

South Korea

Facility Contacts

Geu-Ru Hong, MD, PhD

Role: primary

GRHONG@yuhs.ac

82-2-2228-8443

Other Identifiers

4-2024-0089

Identifier Type: -

Identifier Source: org_study_id