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

NCT05424315 | Completed Phase 2 DMC

• 1 other identifier: CTN1012021
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Anterior MI

Keywords

Heart Failure; Anterior MI; Dapagliflozin; Sodium Glucose Co-transporter 2 inhibitor; Anterior STEMI; Anterior ST Elevation Myocardial Infarction

Outcome Measures

Primary Outcomes (2)

• A change in NT-proBNP levels from baseline to 12 weeks post-anterior STEMI

  Difference between both groups in the change of NT-proBNP levels from baseline to 12 weeks post-anterior STEMI

  12 weeks

• A change in left ventricular ejection fraction, end-diastolic volume or left ventricular mass index assessed by transthoracic echocardiography at baseline, 4 weeks & 12 weeks post-anterior STEMI

  Difference between both groups in the change of the above mentioned echocardiographic parameters assessed at baseline, 4 weeks \& 12 weeks post-anterior STEMI

  12 weeks

Study Arms (2)

Intervention Group

ACTIVE COMPARATOR

Participants will receive Dapagliflozin 10mg once daily.

Drug: Dapagliflozin 10mg

Control Group

PLACEBO COMPARATOR

Participants will receive a glucose tab once daily.

Drug: Glucose Tab

Interventions

Dapagliflozin 10mg DRUG

10mg Tab once daily

Also known as: PubChem CID 9887712, BMS-512148, (1S)-1,5-anhydro-1-C-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}--glucitol, Forxiga, Edistride

Intervention Group

Glucose Tab DRUG

Placebo Oral Tablet

Also known as: PubChem CID 5793, D-Glucose, D-Glc

Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Patients with Diabetes Miletus (Type 1 (DMT2), Type 1 (DMT1), secondary diabetes (e.g., endocrinopathies)
• Patients already diagnosed with heart failure prior to this event
• Patients on cardiotoxic chemotherapeutic medications.
• Patients with haemoglobinopathies.
• Patients with chronic organ damage (i.e., chronic hepatitis with MELD score \>10, Stage 4 \& 5 renal disease).
• Patients already on SGLT2i.
• Patients who will require additional anticoagulant therapy (i.e.: patients with transthoracic echocardiographic evidence of left ventricular thrombus).
• 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.

Sponsors & Collaborators

• Omar Younis: lead
• Ain Shams University: collaborator

Study Sites (2)

Cardiology Department, Faculty of Medicine, Ain Shams University

Cairo, Egypt

Location

National Heart Institute

Cairo, Egypt

Location

Related Publications (14)

• 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.

  PMID: 26378978 RESULT

• Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR; CANVAS Program Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017 Aug 17;377(7):644-657. doi: 10.1056/NEJMoa1611925. Epub 2017 Jun 12.

  PMID: 28605608 RESULT

• 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.

  PMID: 20980548 RESULT

• 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.

  PMID: 25424969 RESULT

• 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.

  PMID: 31535829 RESULT

• 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.

  PMID: 32865377 RESULT

• 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.

  PMID: 32877652 RESULT

• 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.

  PMID: 9789568 RESULT

• 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.

  PMID: 30689697 RESULT

• 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.

  PMID: 30935417 RESULT

• 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.

  PMID: 8443896 RESULT

• 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.

  PMID: 18599344 RESULT

• 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.

  PMID: 21398642 RESULT

• 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.

  PMID: 36889650 DERIVED

MeSH Terms

Conditions

Anterior Wall Myocardial Infarction; Heart Failure

Interventions

dapagliflozin; Glucose

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates

Study Officials

• Khairy Abdul-Dayem, M.D.

  Cardiology Department, Faculty of Medicine, Ain Shams University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Research Coordinator

Study Record Dates

• First Submitted: June 15, 2022
• First Posted: June 21, 2022
• Study Start: October 1, 2021
• Primary Completion: April 30, 2022
• Study Completion: April 30, 2022
• Last Updated: November 19, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Access to the data will be feasible once the results are published.
• Access Criteria: Access to the data will be feasible once the results are published after a formal request to the investigators. Approval of the the investigators is a must.

Locations

EG (2)