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

Sponsor

Instituto Nacional de Cardiologia Ignacio Chavez (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05580510

Collaborator

Boehringer Ingelheim laboratory (Other)

160

Enrollment

Location

Arms

13.7

Anticipated Duration (Months)

11.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Congenital Heart Disease Heart Failure Heart Failure With Reduced Ejection Fraction	Drug: Sacubitril 49 MG / Valsartan 51 MG [Entresto] BID Drug: Empagliflozin 10 MG OD	Phase 2/Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Open-label randomized clinical trialOpen-label randomized clinical trial

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

"An Open-label Clinical Trial to Evaluate the Safety and Efficacy of Empagliflozin and Sacubitril/Valsartan in Adult Patients With Chronic Heart Failure With Reduced Ejection Fraction Associated With Congenital Heart Disease"

Anticipated Study Start Date :

Feb 6, 2023

Anticipated Primary Completion Date :

Jul 28, 2023

Anticipated Study Completion Date :

Mar 29, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Conventional treatment of Heart failure and Sacubitril/Valsartan 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.	Drug: Sacubitril 49 MG / Valsartan 51 MG [Entresto] BID This group of patients will receive the conventional treatment of heart failure according to the "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure" and Sacubitril/Valsartan as an active comparator. Other Names: Entresto
Experimental: Conventional treatment plus Empagliflozin and Sacubitril/valsartan 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.	Drug: Sacubitril 49 MG / Valsartan 51 MG [Entresto] BID This group of patients will receive the conventional treatment of heart failure according to the "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure" and Sacubitril/Valsartan as an active comparator. Other Names: Entresto Drug: Empagliflozin 10 MG OD This group of patients will receive the conventional treatment of heart failure according to the "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure" and Empagliflozin as an experimental drug. Other Names: Jardiance
Experimental: Conventional treatment plus Empagliflozin 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.	Drug: Empagliflozin 10 MG OD This group of patients will receive the conventional treatment of heart failure according to the "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure" and Empagliflozin as an experimental drug. Other Names: Jardiance

Arm

Intervention/Treatment

Active Comparator: Conventional treatment of Heart failure and Sacubitril/Valsartan

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.

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

This group of patients will receive the conventional treatment of heart failure according to the "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure" and Sacubitril/Valsartan as an active comparator.

Other Names:

Entresto

Experimental: Conventional treatment plus Empagliflozin and Sacubitril/valsartan

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.

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

Other Names:

Entresto

Drug: Empagliflozin 10 MG OD

Other Names:

Jardiance

Experimental: Conventional treatment plus Empagliflozin

Drug: Empagliflozin 10 MG OD

Other Names:

Jardiance

Outcome Measures

Primary Outcome Measures

3D echocardiographic systemic ventricular end-diastolic volume index [Twelve weeks]
Change of 8.2 ml or greater in systemic ventricular end-diastolic volume index measured by 3D echocardiogram.
3D echocardiographic systemic ventricular end-systolic volume index [Twelve weeks]
Change of 6.0 ml or greater in end-systolic volume index measured by 3D echocardiogram.

Secondary Outcome Measures

Functional class [Twelve weeks]
A clinically relevant change of greater than or equal to 5 points from baseline score in the functional class measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). This questionnaire evaluates 23 elements and is divided into 7 different domains. The score will interpreted as follows: 0-24 points: very poor to poor 25-49 points: poor to fair 50-74 points: fair to good 75-100 points: good to excellent
Pulmonary congestion [Twelve weeks]
Change in pulmonary B score measured by the quantification and characteristics of B-lines seen with pulmonary ultrasound assessing 8 regions total using the following scoring system: 0 points: less than 3 B-lines per zone 1 point: greater than or equal to 3 B-lines per zone
6-minute walking test [Twelve weeks]
Difference in meters walked in the 6-minute walking test.
Echocardiographic ejection fraction from the systemic ventricle [Twelve weeks]
A change in the percentage of ejection fraction from the systemic ventricle measured by echocardiogram.
Echocardiographic longitudinal overall strain [Twelve weeks]
A change in the percentage of longitudinal overall strain measured by echocardiogram at baseline and after treatment.
NT-proBNP [Twelve weeks]
Change in NT-proBNP values.
Systemic venous congestion [Twelve weeks]
Change in VExUS grading system measured by the diameter of the inferior vena cava in cm and Doppler pattern abnormalities on hepatic, portal and intra-renal veins using the following scoring system: No congestion (0): IVC less than 2 cm Mild (1): IVC greater than or equal to 2cm and any normal or mildly abnormal patterns Moderate (2): IVC greater than or equal to 2cm and ONE severely abnormal pattern Severe (3): IVC greater than or equal to 2 cm and more than or equal to TWO severely abnormal patterns

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institute of Cardiology Ignacio Chavez	Mexico City		Mexico	14080

Sponsors and Collaborators

Instituto Nacional de Cardiologia Ignacio Chavez
Boehringer Ingelheim laboratory

Investigators

Principal Investigator: Edgar Garcia-Cruz, MD, National Institute of Cardiology Ignacio Chavez
Study Chair: Montserrat Villalobos-Pedroza, MD, National Institute of Cardiology Ignacio Chavez
Study Chair: Gian Jimenez-Rodriguez, MD, National Institute of Cardiology Ignacio Chávez
Study Director: Carlos Guizar-Sanchez, MD, National Institute of Cardiology Ignacio Chávez