" Evaluation of Safety and Efficacy of Empagliflozin and Sacubitril/Valsartan for CHF With Reduced Ejection Fraction in ACHD "

National Institute of Cardiology Ignacio Chavez

Status and phase: Not yet enrolling; Phase 3; Phase 2

Conditions: Heart Failure With Reduced Ejection Fraction; Heart Failure; Congenital Heart Disease

Treatments: Drug: Sacubitril 49 MG / Valsartan 51 MG [Entresto] BID; Drug: Empagliflozin 10 MG OD

Study type: Interventional

Funder types: Other

Identifiers

NCT05580510

22-1333

Details and patient eligibility

About

The treatment of adult patients with congenital heart disease (ACHD) and heart failure (HF) represents a great challenge since, to date, there is no standardized guideline for this specific population. Although new treatments for HF have been proposed, such as Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors and neprilisin and angiotensin receptor inhibitors, the benefit of these drugs in patients with HF associated with congenital heart disease in adults has not yet been demonstrated. For this reason, this study pretends to evaluate the efficacy of empagliflozin and sacubitril/valsartan in this population.

Full description

A 12-week randomized, open label, active-controlled trial to explore the effects of once-daily empagliflozin 10 mg and/or sacutril/valsartan 49 mg/51 mg in the reduction of systemic ventricular volumes (end-diastolic and end-systolic) in adult patients with HF associated with congenital heart disease.

Enrollment: 160 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• NYHA functional class II-IV
• Diagnosis of CHD: repaired, palliated or without previous treatment
• Systemic ventricular ejection fraction <40%
• Without unplanned hospital admissions within 3 months prior to randomization
• The participant is willing and able to give informed consent for participation in the study

Exclusion criteria

• Pregnant and postpartum women
• Breastfeeding women during the study
• History of drug allergy to any SGLT-2 inhibitor and/or sacubitril/valsartan
• Previous administration of a drug regimen including an SGLT-2 inhibitor and/or sacubitril/valsartan
• Intellectual or physical disability that impedes the subject to perform the 6 minute walk-test
• Patients with any contraindication to SGLT-2 inhibitor and/or sacubitril/valsartan
• Medical history of myocardial infarction, cardiac surgery or fulminant myocarditis within the last three months
• Medical history of type 1 diabetes mellitus
• Medical history of hypertensive crisis in the previous 6-months
• Medical history of cardiogenic shock or heart failure decompensation in the previous 6-months
• Medical history of heart transplantation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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160 participants in 3 patient groups

Conventional treatment of Heart failure and Sacubitril/Valsartan

Active Comparator group

Description:

Patients will receive conventional treatment consisting of spironolactone 25 mg orally every 24 hours (maximum dose 50 mg every 24 hours) or eplerenone 25 mg orally every 24 hours (maximum dose 50 mg every 24 hours); beta-blockers: bisoprolol 1.5 mg orally every 24 hours (maximum dose 10 mg every 24 hours) or metoprolol succinate 12.5 mg every 24 hours orally (maximum dose 200 mg every 24 hours) or carvedilol 3125 mg every 24 hours (maximum dose 25 mg every 24 hours) or ivabradine 5 mg every 12 hours (maximum dose 7.5 mg every 12 hours); diuretics: furosemide 20 to 400 mg orally every 24 hours or bumetanide 1 to 15 mg orally every 24 hours and/or chlorthalidone 25 mg orally every 24 hours. Additionally, patients will receive Sacubitril/Valsartan, with the intention to titrate up to 49 mg/51 mg orally every 12 hours.

Treatment:

Drug: Sacubitril 49 MG / Valsartan 51 MG [Entresto] BID

Conventional treatment plus Empagliflozin and Sacubitril/valsartan

Experimental group

Description:

Patients will receive conventional treatment consisting of spironolactone 25 mg orally every 24 hours (maximum dose 50 mg every 24 hours) or eplerenone 25 mg orally every 24 hours (maximum dose 50 mg every 24 hours); beta-blockers: bisoprolol 1.5 mg orally every 24 hours (maximum dose 10 mg every 24 hours) or metoprolol succinate 12.5 mg every 24 hours orally (maximum dose 200 mg every 24 hours) or carvedilol 3125 mg every 24 hours (maximum dose 25 mg every 24 hours) or ivabradine 5 mg every 12 hours (maximum dose 7.5 mg every 12 hours); diuretics: furosemide 20 to 400 mg orally every 24 hours or bumetanide 1 to 15 mg orally every 24 hours and/or chlorthalidone 25 mg orally every 24 hours. Additionally, patients will use Sacubitril/Valsartan, with the intention to titrate up to 49 mg/51 mg orally every 12 hours and Empagliflozin 10 mg orally every 24 hours.

Treatment:

Drug: Empagliflozin 10 MG OD

Drug: Sacubitril 49 MG / Valsartan 51 MG [Entresto] BID

Conventional treatment plus Empagliflozin

Experimental group

Description:

Patients will receive conventional treatment consisting of spironolactone 25 mg orally every 24 hours (maximum dose 50 mg every 24 hours) or eplerenone 25 mg orally every 24 hours (maximum dose 50 mg every 24 hours); beta-blockers: bisoprolol 1.5 mg orally every 24 hours (maximum dose 10 mg every 24 hours) or metoprolol succinate 12.5 mg every 24 hours orally (maximum dose 200 mg every 24 hours) or carvedilol 3125 mg every 24 hours (maximum dose 25 mg every 24 hours) or ivabradine 5 mg every 12 hours (maximum dose 7.5 mg every 12 hours); diuretics: furosemide 20 to 400 mg orally every 24 hours or bumetanide 1 to 15 mg orally every 24 hours and/or chlorthalidone 25 mg orally every 24 hours. Additionally, patients will use Empagliflozin 10 mg orally every 24 hours.

Treatment:

Drug: Empagliflozin 10 MG OD