Impact of DApagliflozin on Cardiac Function Following Anterior Myocardial Infarction in Non-Diabetic Patients

NCT ID: NCT05424315

Last Updated: 2024-11-19

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

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-01

Study Completion Date

2022-04-30

Brief Summary

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Sodium glucose co-transporter 2 inhibitors (SGLT2i) proved their favorable outcomes in heart failure. However, it is still unknown if their role extent into preventing heart failure, especially after acute myocardial infarction. This study aimed at identifying if there is such role for SGLT2i.

Detailed Description

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A notable breakthrough in the management of heart failure is the use of a class of anti-diabetic medications known as, gliflozins. Gliflozins act by inhibiting the sodium glucose co-transporter 2 (SGLT-2). This is a transmembrane protein found at the luminal border of tubular cells of the proximal convoluted tubules of the kidney. It accounts for around 90% of glucose re-absorption. Inhibiting the SGLT-2 results in better glycemic control in patient with diabetes mellitus type 2 (DMT2).

In heart failure, sodium glucose co-transporter 2 inhibitors (SGLT2i - i.e., gliflozins) were found to have a favorable cardiovascular outcome independent of their anti-glycemic effect. In patients with acute myocardial infarction, the heart function as a pump is affected \& heart failure develops. In particular, patients with anterior ST-elevation myocardial infarction (STEMI) are at a higher risk of remodeling \& heart failure. This is due to the cutoff in blood supply in the left anterior descending (LAD) coronary artery which supplies a great area of left ventricle.

A question that rises: is there a role for SGLT2i, \& in particular dapagliflozin, in acute myocardial infarction in improving post-infarction cardiac function \& preventing heart failure? especially in patients who experience Anterior ST-Elevation Myocardial Infarction (STEMI).

Conditions

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Anterior MI

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Intervention Group

Participants will receive Dapagliflozin 10mg once daily.

Group Type ACTIVE_COMPARATOR

Dapagliflozin 10mg

Intervention Type DRUG

10mg Tab once daily

Control Group

Participants will receive a glucose tab once daily.

Group Type PLACEBO_COMPARATOR

Glucose Tab

Intervention Type DRUG

Placebo Oral Tablet

Interventions

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Dapagliflozin 10mg

10mg Tab once daily

Intervention Type DRUG

Glucose Tab

Placebo Oral Tablet

Intervention Type DRUG

Other Intervention Names

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PubChem CID 9887712 BMS-512148 (1S)-1,5-anhydro-1-C-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}--glucitol Forxiga Edistride PubChem CID 5793 D-Glucose D-Glc

Eligibility Criteria

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Inclusion Criteria

* Patients admitted with ECG Criteria for Anterior ST-elevation myocardial infarction according to the fourth universal definition of myocardial infarction\*, \*\* \& show echocardiographic evidence of reduced LV ejection fraction \<50% \& have undergone successful reperfusion by primary percutaneous coronary angiography (pPCI).

* New ST segment elevation in contagious precordial leads consistent anatomically with the anterior wall of myocardium:

* Men ≥ 40 years: 2 mV in leads V2-V3 \&/or 1 mV in other precordial leads
* Men \<40 years: 2.5 mV in leads V2-V3 \&/or 1 mV in other precordial leads
* Women (regardless of age): 1.5 mV in leads V2-V3 \&/or 1 mV in other precordial leads \*\* Patients with admission ECG showing DeWinter's Syndrome, Wellen Syndrome, New onset left bundle branch block, new onset right bundle branch block will also be included.

Exclusion Criteria

1. Patients with Diabetes Miletus (Type 1 (DMT2), Type 1 (DMT1), secondary diabetes (e.g., endocrinopathies)
2. Patients already diagnosed with heart failure prior to this event
3. Patients on cardiotoxic chemotherapeutic medications.
4. Patients with haemoglobinopathies.
5. Patients with chronic organ damage (i.e., chronic hepatitis with MELD score \>10, Stage 4 \& 5 renal disease).
6. Patients already on SGLT2i.
7. Patients who will require additional anticoagulant therapy (i.e.: patients with transthoracic echocardiographic evidence of left ventricular thrombus).
8. Patients with contraindications for use of dapagliflozin including patients with severely impaired renal function (eGFR \<30ml/min/1.73m2) \&/OR previous history of genitourinary infections (i.e.: urosepsis, pyelonephritis \& fournier's gangrene) \&/OR at high risk of such infections.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ain Shams University

OTHER

Sponsor Role collaborator

Omar Younis

OTHER_GOV

Sponsor Role lead

Responsible Party

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Omar Younis

Clinical Research Coordinator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Khairy Abdul-Dayem, M.D.

Role: PRINCIPAL_INVESTIGATOR

Cardiology Department, Faculty of Medicine, Ain Shams University

Locations

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Cardiology Department, Faculty of Medicine, Ain Shams University

Cairo, , Egypt

Site Status

National Heart Institute

Cairo, , Egypt

Site Status

Countries

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Egypt

References

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Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28. doi: 10.1056/NEJMoa1504720. Epub 2015 Sep 17.

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Hummel CS, Lu C, Loo DD, Hirayama BA, Voss AA, Wright EM. Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2. Am J Physiol Cell Physiol. 2011 Jan;300(1):C14-21. doi: 10.1152/ajpcell.00388.2010. Epub 2010 Oct 27.

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Kalra S. Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors: A Review of Their Basic and Clinical Pharmacology. Diabetes Ther. 2014 Dec;5(2):355-66. doi: 10.1007/s13300-014-0089-4. Epub 2014 Nov 26.

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McMurray JJV, Solomon SD, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Belohlavek J, Bohm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukat A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjostrand M, Langkilde AM; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019 Nov 21;381(21):1995-2008. doi: 10.1056/NEJMoa1911303. Epub 2019 Sep 19.

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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)

Zannad F, Ferreira JP, Pocock SJ, Anker SD, Butler J, Filippatos G, Brueckmann M, Ofstad AP, Pfarr E, Jamal W, Packer M. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet. 2020 Sep 19;396(10254):819-829. doi: 10.1016/S0140-6736(20)31824-9. Epub 2020 Aug 30.

Reference Type RESULT
PMID: 32877652 (View on PubMed)

Wright EM, Loo DD, Panayotova-Heiermann M, Hirayama BA, Turk E, Eskandari S, Lam JT. Structure and function of the Na+/glucose cotransporter. Acta Physiol Scand Suppl. 1998 Aug;643:257-64.

Reference Type RESULT
PMID: 9789568 (View on PubMed)

Shi L, Zhu D, Wang S, Jiang A, Li F. Dapagliflozin Attenuates Cardiac Remodeling in Mice Model of Cardiac Pressure Overload. Am J Hypertens. 2019 Apr 22;32(5):452-459. doi: 10.1093/ajh/hpz016.

Reference Type RESULT
PMID: 30689697 (View on PubMed)

Lee HC, Shiou YL, Jhuo SJ, Chang CY, Liu PL, Jhuang WJ, Dai ZK, Chen WY, Chen YF, Lee AS. The sodium-glucose co-transporter 2 inhibitor empagliflozin attenuates cardiac fibrosis and improves ventricular hemodynamics in hypertensive heart failure rats. Cardiovasc Diabetol. 2019 Apr 1;18(1):45. doi: 10.1186/s12933-019-0849-6.

Reference Type RESULT
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Gaudron P, Eilles C, Kugler I, Ertl G. Progressive left ventricular dysfunction and remodeling after myocardial infarction. Potential mechanisms and early predictors. Circulation. 1993 Mar;87(3):755-63. doi: 10.1161/01.cir.87.3.755.

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Santoro GM, Carrabba N, Migliorini A, Parodi G, Valenti R. Acute heart failure in patients with acute myocardial infarction treated with primary percutaneous coronary intervention. Eur J Heart Fail. 2008 Aug;10(8):780-5. doi: 10.1016/j.ejheart.2008.06.004. Epub 2008 Jul 2.

Reference Type RESULT
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Masci PG, Ganame J, Francone M, Desmet W, Lorenzoni V, Iacucci I, Barison A, Carbone I, Lombardi M, Agati L, Janssens S, Bogaert J. Relationship between location and size of myocardial infarction and their reciprocal influences on post-infarction left ventricular remodelling. Eur Heart J. 2011 Jul;32(13):1640-8. doi: 10.1093/eurheartj/ehr064. Epub 2011 Mar 12.

Reference Type RESULT
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Dayem KA, Younis O, Zarif B, Attia S, AbdelSalam A. Impact of dapagliflozin on cardiac function following anterior myocardial infarction in non-diabetic patients - DACAMI (a randomized controlled clinical trial). Int J Cardiol. 2023 May 15;379:9-14. doi: 10.1016/j.ijcard.2023.03.002. Epub 2023 Mar 6.

Reference Type DERIVED
PMID: 36889650 (View on PubMed)

Other Identifiers

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CTN1012021

Identifier Type: -

Identifier Source: org_study_id

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