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

October 31, 2022 updated by: Instituto Nacional de Cardiologia Ignacio Chavez

"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"

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

160

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
3D echocardiographic systemic ventricular end-diastolic volume index
Time Frame: Twelve weeks
Change of 8.2 ml or greater in systemic ventricular end-diastolic volume index measured by 3D echocardiogram.
Twelve weeks
3D echocardiographic systemic ventricular end-systolic volume index
Time Frame: Twelve weeks
Change of 6.0 ml or greater in end-systolic volume index measured by 3D echocardiogram.
Twelve weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Functional class
Time Frame: 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
Twelve weeks
Pulmonary congestion
Time Frame: 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
Twelve weeks
6-minute walking test
Time Frame: Twelve weeks
Difference in meters walked in the 6-minute walking test.
Twelve weeks
Echocardiographic ejection fraction from the systemic ventricle
Time Frame: Twelve weeks
A change in the percentage of ejection fraction from the systemic ventricle measured by echocardiogram.
Twelve weeks
Echocardiographic longitudinal overall strain
Time Frame: Twelve weeks
A change in the percentage of longitudinal overall strain measured by echocardiogram at baseline and after treatment.
Twelve weeks
NT-proBNP
Time Frame: Twelve weeks
Change in NT-proBNP values.
Twelve weeks
Systemic venous congestion
Time Frame: 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
Twelve weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Nacional de Cardiologia Ignacio Chavez

Collaborators

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 Chavez
  • Study Director: Carlos Guizar-Sanchez, MD, National Institute of Cardiology Ignacio Chavez

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

February 6, 2023

Primary Completion (Anticipated)

July 28, 2023

Study Completion (Anticipated)

March 29, 2024

Study Registration Dates

First Submitted

October 4, 2022

First Submitted That Met QC Criteria

October 11, 2022

First Posted (Actual)

October 14, 2022

Study Record Updates

Last Update Posted (Actual)

November 2, 2022

Last Update Submitted That Met QC Criteria

October 31, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22-1333

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe