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

NCT ID: NCT05580510

Last Updated: 2022-11-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE2/PHASE3

Total Enrollment

160 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-06

Study Completion Date

2024-03-29

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Congenital Heart Disease Heart Failure Heart Failure With Reduced Ejection Fraction

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Open-label randomized clinical trial
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type ACTIVE_COMPARATOR

Sacubitril 49 MG / Valsartan 51 MG [Entresto] BID

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

Sacubitril 49 MG / Valsartan 51 MG [Entresto] BID

Intervention Type DRUG

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

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

Empagliflozin 10 MG OD

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Entresto Jardiance

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Boehringer Ingelheim

INDUSTRY

Sponsor Role collaborator

Instituto Nacional de Cardiologia Ignacio Chavez

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Edgar Garcia-Cruz, MD

Role: PRINCIPAL_INVESTIGATOR

National Institute of Cardiology Ignacio Chavez

Montserrat Villalobos-Pedroza, MD

Role: STUDY_CHAIR

National Institute of Cardiology Ignacio Chavez

Gian Jimenez-Rodriguez, MD

Role: STUDY_CHAIR

National Institute of Cardiology Ignacio Chávez

Carlos Guizar-Sanchez, MD

Role: STUDY_DIRECTOR

National Institute of Cardiology Ignacio Chávez

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

National Institute of Cardiology Ignacio Chavez

Mexico City, , Mexico

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Mexico

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Edgar Garcia-Cruz, MD

Role: CONTACT

+ 52 55 4340 7152

Daniel Manzur-Sandoval, MD

Role: CONTACT

+ 52 55 1291 1916

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Edgar García-Cruz, MD

Role: primary

+ 52 55 4340 7152

Daniel Manzur-Sandoval, MD

Role: backup

+ 52 55 1291 1916

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 30415601 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33030857 (View on PubMed)

McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm 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. No abstract available.

Reference Type BACKGROUND
PMID: 34447992 (View on PubMed)

Budts W, Roos-Hesselink J, Radle-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. No abstract available.

Reference Type BACKGROUND
PMID: 26787434 (View on PubMed)

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.

Reference Type BACKGROUND

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. No abstract available.

Reference Type BACKGROUND
PMID: 26787728 (View on PubMed)

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.

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 33960724 (View on PubMed)

Jhund PS, Ponikowski P, Docherty KF, Gasparyan SB, Bohm M, Chiang CE, Desai AS, Howlett J, Kitakaze M, Petrie MC, Verma S, Bengtsson O, Langkilde AM, Sjostrand M, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Sabatine MS, Solomon SD, McMurray JJV. Dapagliflozin and Recurrent Heart Failure Hospitalizations in Heart Failure With Reduced Ejection Fraction: An Analysis of DAPA-HF. Circulation. 2021 May 18;143(20):1962-1972. doi: 10.1161/CIRCULATIONAHA.121.053659. Epub 2021 Apr 9.

Reference Type RESULT
PMID: 33832352 (View on PubMed)

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, Bohm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F; EMPEROR-Reduced Trial Investigators. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020 Oct 8;383(15):1413-1424. doi: 10.1056/NEJMoa2022190. Epub 2020 Aug 28.

Reference Type RESULT
PMID: 32865377 (View on PubMed)

Bauersachs J. Heart failure drug treatment: the fantastic four. Eur Heart J. 2021 Feb 11;42(6):681-683. doi: 10.1093/eurheartj/ehaa1012. No abstract available.

Reference Type RESULT
PMID: 33447845 (View on PubMed)

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, Radjenovic A, Mark PB, McMurray JJV, Jhund PS, Petrie MC, Sattar N. Effect of Empagliflozin on Left Ventricular Volumes in Patients With Type 2 Diabetes, or Prediabetes, and Heart Failure With Reduced Ejection Fraction (SUGAR-DM-HF). Circulation. 2021 Feb 9;143(6):516-525. doi: 10.1161/CIRCULATIONAHA.120.052186. Epub 2020 Nov 13.

Reference Type RESULT
PMID: 33186500 (View on PubMed)

Nougue 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 study. Eur J Heart Fail. 2019 May;21(5):598-605. doi: 10.1002/ejhf.1342. Epub 2018 Dec 6.

Reference Type RESULT
PMID: 30520545 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

22-1333

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.