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Congenital Heart DiseasePhase 2/3NCT05580510

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

A Phase 2/3 study testing Sacubitril 49 MG / Valsartan 51 MG [Entresto] BID and Empagliflozin 10 MG OD in people with Congenital Heart Disease and Heart Failure, run by Instituto Nacional de Cardiologia Ignacio Chavez at 1 site in Mexico.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Sacubitril 49 MG / Valsartan 51 MG [Entresto] BID and Empagliflozin 10 MG OD
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
160 participants
Where
1 siteMexico
Study dates
6 Feb 2023to 29 Mar 2024
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Edgar Garcia-Cruz, MD contact

+ 52 55 4340 7152

Edgar.garcia@cardiologia.org.mx

Daniel Manzur-Sandoval, MD contact

+ 52 55 1291 1916

drdanielmanzur@gmail.com

Mexico1 site

  • National Institute of Cardiology Ignacio Chavez

    Mexico City, 14080

    Edgar García-Cruz, MD, + 52 55 4340 7152, Edgar.garcia@cardiologia.org.mx

    Daniel Manzur-Sandoval, MD, + 52 55 1291 1916, drdanielmanzur@gmail.com

Other trials in Mexico

About this study

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"

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.

Read the 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.

Being tested
Sacubitril 49 MG / Valsartan 51 MG [Entresto] BID, Empagliflozin 10 MG OD
Keywords
Adult congenital heart disease, Heart Failure with Reduced Ejection Fraction, Empagliflozin, Sacubitril-valsartan
Medical subject headings
Heart Defects, Congenital, Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sacubitril 49 MG / Valsartan 51 MG [Entresto] BIDDrug

    Also called Entresto

    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 ODDrug

    Also called Jardiance

    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.

Study groups in NCT05580510
Study groupRoleWhat they receive
Conventional treatment of Heart failure and Sacubitril/ValsartanActive comparatorPatients 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.
Receives: Drug: Sacubitril 49 MG / Valsartan 51 MG [Entresto] BID
Conventional treatment plus Empagliflozin and Sacubitril/valsartanExperimentalPatients 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.
Receives: Drug: Sacubitril 49 MG / Valsartan 51 MG [Entresto] BID; Drug: Empagliflozin 10 MG OD
Conventional treatment plus EmpagliflozinExperimentalPatients 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.
Receives: Drug: Empagliflozin 10 MG OD

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Twelve weeks

  2. 3D echocardiographic systemic ventricular end-systolic volume index

    Change of 6.0 ml or greater in end-systolic volume index measured by 3D echocardiogram.

    Measured: Twelve weeks

Secondary outcomes (7)

  1. 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

    Measured: Twelve weeks

  2. 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

    Measured: Twelve weeks

  3. 6-minute walking test

    Difference in meters walked in the 6-minute walking test.

    Measured: Twelve weeks

  4. Echocardiographic ejection fraction from the systemic ventricle

    A change in the percentage of ejection fraction from the systemic ventricle measured by echocardiogram.

    Measured: Twelve weeks

  5. Echocardiographic longitudinal overall strain

    A change in the percentage of longitudinal overall strain measured by echocardiogram at baseline and after treatment.

    Measured: Twelve weeks

  6. NT-proBNP

    Change in NT-proBNP values.

    Measured: Twelve weeks

  7. 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

    Measured: Twelve weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Oct 2022
  2. Study start6 Feb 2023 (estimated)
  3. Primary completion28 Jul 2023 (estimated)
  4. Study completion29 Mar 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Open-label randomized clinical trial
Masking
None (open label)
Enrolment
160 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05580510
Sponsor's protocol ID
22-1333
Status last verified
Oct 2022
First submitted
4 Oct 2022
Last updated
2 Nov 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 30415601

  • 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.

    PubMed 33030857

  • 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.

    PubMed 34447992

  • 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.

    PubMed 26787434

  • 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.

  • 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.

    PubMed 26787728

  • 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.

  • 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.

    PubMed 33960724

  • 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.

    PubMed 33832352

  • 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.

    PubMed 32865377

  • 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.

    PubMed 33447845

  • 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.

    PubMed 33186500

  • 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.

    PubMed 30520545

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Sacubitril 49 MG / Valsartan 51 MG [Entresto] BID and Empagliflozin 10 MG OD in people with Congenital Heart Disease and Heart Failure, run by Instituto Nacional de Cardiologia Ignacio Chavez at 1 site in Mexico.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 2 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Edgar Garcia-Cruz, MD (+ 52 55 4340 7152, Edgar.garcia@cardiologia.org.mx), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

3D echocardiographic systemic ventricular end-diastolic volume index (time frame: Twelve weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05580510, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2022.

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