Congenital Heart Disease, Heart Failure, Heart Failure With Reduced Ejection Fraction
Conditions
Keywords
Adult congenital heart disease, Heart Failure with Reduced Ejection Fraction, Empagliflozin, Sacubitril-valsartan
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.
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.
Interventions
DRUGSacubitril 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.
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.
Sponsors
Boehringer Ingelheim
Instituto Nacional de Cardiologia Ignacio Chavez
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label randomized clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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 |
| Echocardiographic longitudinal overall strain | Twelve weeks | A change in the percentage of longitudinal overall strain measured by echocardiogram at baseline and after treatment. |
| 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 |
Countries
Mexico
Contacts
Primary ContactEdgar Garcia-Cruz, MD
Backup ContactDaniel Manzur-Sandoval, MD
Outcome results
None listed