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

Heart Failure Clinical Trial

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"

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05580510
• Other study ID #: 22-1333
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: February 6, 2023
• Est. completion date: March 29, 2024

Study information

• Verified date: October 2022
• Source: Instituto Nacional de Cardiologia Ignacio Chavez
• Contact: Edgar Garcia-Cruz, MD
• Phone: + 52 55 4340 7152
• Email: Edgar.garcia[@]cardiologia.org.mx
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 160
• Est. completion date: March 29, 2024
• Est. primary completion date: July 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Congenital Heart Disease
• Heart Defects, Congenital
• Heart Diseases
• Heart Failure
• Heart Failure With Reduced Ejection Fraction

Intervention

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.
• 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.

Locations

Country	Name	City	State
Mexico	National Institute of Cardiology Ignacio Chavez	Mexico City

Sponsors (2)

Lead Sponsor	Collaborator
Instituto Nacional de Cardiologia Ignacio Chavez	Boehringer Ingelheim laboratory

Country where clinical trial is conducted

Mexico, 

References & Publications (13)

Arnaert S, De Meester P, Troost E, Droogne W, Van Aelst L, Van Cleemput J, Voros G, Gewillig M, Cools B, Moons P, Rega F, Meyns B, Zhang Z, Budts W, Van De Bruaene A. Heart failure related to adult congenital heart disease: prevalence, outcome and risk factors. ESC Heart Fail. 2021 Aug;8(4):2940-2950. doi: 10.1002/ehf2.13378. Epub 2021 May 7. — View Citation

Bauersachs J. Heart failure drug treatment: the fantastic four. Eur Heart J. 2021 Feb 11;42(6):681-683. doi: 10.1093/eurheartj/ehaa1012. — View Citation

Budts W, Roos-Hesselink J, Rädle-Hurst T, Eicken A, McDonagh TA, Lambrinou E, Crespo-Leiro MG, Walker F, Frogoudaki AA. Treatment of heart failure in adult congenital heart disease: a position paper of the Working Group of Grown-Up Congenital Heart Disease and the Heart Failure Association of the European Society of Cardiology. Eur Heart J. 2016 May 7;37(18):1419-27. doi: 10.1093/eurheartj/ehv741. Epub 2016 Jan 18. Review. — View Citation

Hu J, Wu Y, Zhou X, Wang X, Jiang W, Huo J, Shan Q. Beneficial Effects of Sacubitril/Valsartan at Low Doses in an Asian Real-World Heart Failure Population. J Cardiovasc Pharmacol. 2020 Oct;76(4):445-451. doi: 10.1097/FJC.0000000000000873. — View Citation

Jhund PS, Ponikowski P, Docherty KF, Gasparyan SB, Böhm M, Chiang CE, Desai AS, Howlett J, Kitakaze M, Petrie MC, Verma S, Bengtsson O, Langkilde AM, Sjöstrand M, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Sabatine MS, Solomon SD, McMurray JJV. Dapa — View Citation

Konstatinos D. Alonso- González R, D'alto M. Heart Failure, Exercise Intolerance and Physical Training. Chapter 7, Part I General Principles. Diagnosis and Management of Adult Congenital Heart Disease. (2017): 77-87.

Lee MMY, Brooksbank KJM, Wetherall K, Mangion K, Roditi G, Campbell RT, Berry C, Chong V, Coyle L, Docherty KF, Dreisbach JG, Labinjoh C, Lang NN, Lennie V, McConnachie A, Murphy CL, Petrie CJ, Petrie JR, Speirits IA, Sourbron S, Welsh P, Woodward R, Radj — View Citation

Marelli, A. Gatzoulis, M. Gary, D. Webb, Piers E.F. Daubeney. Adults With Congenital Heart Disease: A Growing Population. Chapter 1 Part I General Principles. Diagnosis and Management of Adult Congenital Heart Disease. (2017): 2-9.

McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. Erratum in: Eur Heart J. 2021 Oct 14;:. — View Citation

Nougué H, Pezel T, Picard F, Sadoune M, Arrigo M, Beauvais F, Launay JM, Cohen-Solal A, Vodovar N, Logeart D. Effects of sacubitril/valsartan on neprilysin targets and the metabolism of natriuretic peptides in chronic heart failure: a mechanistic clinical — View Citation

Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Böhm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Jua — View Citation

Stout KK, Broberg CS, Book WM, Cecchin F, Chen JM, Dimopoulos K, Everitt MD, Gatzoulis M, Harris L, Hsu DT, Kuvin JT, Law Y, Martin CM, Murphy AM, Ross HJ, Singh G, Spray TL; American Heart Association Council on Clinical Cardiology, Council on Functional Genomics and Translational Biology, and Council on Cardiovascular Radiology and Imaging. Chronic Heart Failure in Congenital Heart Disease: A Scientific Statement From the American Heart Association. Circulation. 2016 Feb 23;133(8):770-801. doi: 10.1161/CIR.0000000000000352. Epub 2016 Jan 19. Review. — View Citation

Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCague K, Rocha R, Braunwald E; PIONEER-HF Investigators. Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure. N Engl J Med. 2019 Feb 7;380(6):539-548. doi: 10.1056/NEJMoa1812851. Epub 2018 Nov 11. Erratum in: N Engl J Med. 2019 Mar 14;380(11):1090. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	3D echocardiographic systemic ventricular end-diastolic volume index	Change of 8.2 ml or greater in systemic ventricular end-diastolic volume index measured by 3D echocardiogram.	Twelve weeks
Primary	3D echocardiographic systemic ventricular end-systolic volume index	Change of 6.0 ml or greater in end-systolic volume index measured by 3D echocardiogram.	Twelve weeks
Secondary	Functional class	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
Secondary	Pulmonary congestion	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
Secondary	6-minute walking test	Difference in meters walked in the 6-minute walking test.	Twelve weeks
Secondary	Echocardiographic ejection fraction from the systemic ventricle	A change in the percentage of ejection fraction from the systemic ventricle measured by echocardiogram.	Twelve weeks
Secondary	Echocardiographic longitudinal overall strain	A change in the percentage of longitudinal overall strain measured by echocardiogram at baseline and after treatment.	Twelve weeks
Secondary	NT-proBNP	Change in NT-proBNP values.	Twelve weeks
Secondary	Systemic venous congestion	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