Effect of Dapagliflozin Administration on the Apoptosis Levels of Patients With Acute Myocardial Infarction

NCT06615674 | Completed Phase 4 DMC

• 1 other identifier: S5121020014865
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The currently known Sodium-Glucose Transporter 2 (SGLT-2) inhibitors are recognized not only for their effects on improving intravascular glucose levels but also for their cardioprotective effects, including improvements in endothelial dysfunction, inhibition of platelet activation, reduction in autophagy processes, oxidative stress, and inflammation, as well as inhibition of the Na+/H+ exchanger pathway, which potentially reduces cell damage and death resulting from ischemia and reperfusion processes. Research on the benefits of SGLT-2 inhibitors in pre-clinical studies with myocardial infarction has shown a significant reduction in myocardial apoptosis, indicated by reduced levels of caspase-3 and the apoptosis index. Additionally, there was an increase in ketone bodies and myocardial ATP, reduced levels of inflammatory cytokines, free radicals, and infarct area, as well as improvements in left ventricular ejection fraction. However, large-scale studies in humans have thus far been limited to investigating the effects of SGLT-2 inhibitors on mortality, rehospitalization rates due to heart failure, cardiometabolic factors, and improvements in remodeling parameters in myocardial infarction patients, with the use of empagliflozin or dapagliflozin. Based on literature reviews, there have been no studies to date that directly demonstrate the effects of dapagliflozin on apoptosis (caspase-3 levels) in myocardial infarction patients.

Conditions

Acute Myocardial Infarction (AMI); STEMI - ST Elevation Myocardial Infarction (MI); NSTEMI - Non-ST Segment Elevation Myocardial Infarction (MI)

Keywords

AMI; STEMI; NSTEMI; Dapagliflozin; Apoptosis; Caspase-3; Myocardial Work

Outcome Measures

Primary Outcomes (1)

• Change in Biomolecular Parameters

  Change in Caspase-3 (ng/L) level in blood serum patients

  14 days

Secondary Outcomes (1)

• Change in Echocardiographic Parameters

  14 days

Study Arms (2)

Dapagliflozin

EXPERIMENTAL

The intervention group will have dapagliflozin 10mg once a day every morning besides standard treatment of Acute Coronary Syndrome for 14 days before further evaluation

Drug: Forxiga® 10 mg Film-Coated Tablet, manufactured by AstraZeneca Pharmaceuticals LP, USA for AstraZeneca Pharmaceuticals Co. Ltd., China imported by PT AstraZeneca Indonesia, Indonesia

Control

EXPERIMENTAL

The first group is the Dapagliflozin group, which will get Dapagliflozin 10mg once a day every morning for 14 days. And the second group will have placebo for 14 days.

Drug: Forxiga® 10 mg Film-Coated Tablet, manufactured by AstraZeneca Pharmaceuticals LP, USA for AstraZeneca Pharmaceuticals Co. Ltd., China imported by PT AstraZeneca Indonesia, Indonesia

Interventions

Forxiga® 10 mg Film-Coated Tablet, manufactured by AstraZeneca Pharmaceuticals LP, USA for AstraZeneca Pharmaceuticals Co. Ltd., China imported by PT AstraZeneca Indonesia, Indonesia DRUG

The first group is the Dapagliflozin group, which will get Dapagliflozin 10mg once a day every morning for 14 days. And the second group will have placebo for 14 days.

Control; Dapagliflozin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with Acute Myocardial Infarction (STEMI or NSTEMI) according to the Fourth Universal Definition of Myocardial Infarction from the European Society of Cardiology, American College of Cardiology, American Heart Association, and World Heart Federation.
• Aged 18-75 years
• Willing to participate in the study and sign informed consent.

You may not qualify if:

• Patients with cardiogenic shock (SBP ≤ 80 mmHg, cold extremities, urine output \<0.5 ml/kg/hr) \<24 hours before randomization
• Patients with ketoacidosis (arterial pH \<7.30, serum bicarbonate \<18 mEq/l, positive ketonuria)
• Patients with impaired renal function with an estimated glomerular filtration rate (eGFR) \<20 ml/min or requiring dialysis
• Patients with a history of chronic heart failure before the onset of Acute Myocardial Infarction
• Patients scheduled for coronary artery bypass surgery
• Patients with type 1 diabetes mellitus
• Patients with severe valvular disease
• Patients with sepsis
• Patients with symptomatic acute urinary tract infection
• Pregnant patients
• Patients with severe aortic stenosis or LVOT obstruction

Sponsors & Collaborators

• Yoga Yudhistira: lead

Study Sites (1)

Dr. Moewardi General Hospital, Jebres, Surakarta, Central of Java, 57126

Surakarta, Central of Java, 57126, Indonesia

Location

Related Publications (7)

• James S, Erlinge D, Storey RF, McGuire DK, de Belder M, Eriksson N, Andersen K, Austin D, Arefalk G, Carrick D, Hofmann R, Hoole SP, Jones DA, Lee K, Tygesen H, Johansson PA, Langkilde AM, Ridderstrale W, Parvaresh Rizi E, Deanfield J, Oldgren J. Dapagliflozin in Myocardial Infarction without Diabetes or Heart Failure. NEJM Evid. 2024 Feb;3(2):EVIDoa2300286. doi: 10.1056/EVIDoa2300286. Epub 2023 Nov 11.

  PMID: 38320489 BACKGROUND

• Hernandez AF, Udell JA, Jones WS, Anker SD, Petrie MC, Harrington J, Mattheus M, Seide S, Zwiener I, Amir O, Bahit MC, Bauersachs J, Bayes-Genis A, Chen Y, Chopra VK, A Figtree G, Ge J, G Goodman S, Gotcheva N, Goto S, Gasior T, Jamal W, Januzzi JL, Jeong MH, Lopatin Y, Lopes RD, Merkely B, Parikh PB, Parkhomenko A, Ponikowski P, Rossello X, Schou M, Simic D, Steg PG, Szachniewicz J, van der Meer P, Vinereanu D, Zieroth S, Brueckmann M, Sumin M, Bhatt DL, Butler J. Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights From the EMPACT-MI Trial. Circulation. 2024 May 21;149(21):1627-1638. doi: 10.1161/CIRCULATIONAHA.124.069217. Epub 2024 Apr 6.

  PMID: 38581389 BACKGROUND

• Tanajak P, Sa-Nguanmoo P, Sivasinprasasn S, Thummasorn S, Siri-Angkul N, Chattipakorn SC, Chattipakorn N. Cardioprotection of dapagliflozin and vildagliptin in rats with cardiac ischemia-reperfusion injury. J Endocrinol. 2018 Feb;236(2):69-84. doi: 10.1530/JOE-17-0457. Epub 2017 Nov 15.

  PMID: 29142025 BACKGROUND

• Jin W, Wang L, Zhu T, Ma Y, Yu C, Zhang F. Usefulness of echocardiographic myocardial work in evaluating the microvascular perfusion in STEMI patients after revascularization. BMC Cardiovasc Disord. 2022 May 13;22(1):218. doi: 10.1186/s12872-022-02648-z.

  PMID: 35562649 BACKGROUND

• Chen S, Coronel R, Hollmann MW, Weber NC, Zuurbier CJ. Direct cardiac effects of SGLT2 inhibitors. Cardiovasc Diabetol. 2022 Mar 18;21(1):45. doi: 10.1186/s12933-022-01480-1.

  PMID: 35303888 BACKGROUND

• McIlwain DR, Berger T, Mak TW. Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol. 2015 Apr 1;7(4):a026716. doi: 10.1101/cshperspect.a026716. No abstract available.

  PMID: 25833847 BACKGROUND

• Teringova E, Tousek P. Apoptosis in ischemic heart disease. J Transl Med. 2017 May 1;15(1):87. doi: 10.1186/s12967-017-1191-y.

  PMID: 28460644 BACKGROUND

MeSH Terms

Conditions

ST Elevation Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Spinocerebellar Ataxias

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Cerebellar Ataxia; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Ataxia; Dyskinesias; Neurologic Manifestations; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Yoga Yudhistira MD

  Dr. Moewardi General Hospital, Jebres, Surakarta, Central of Java, 57126

  PRINCIPAL INVESTIGATOR

• Ahmad Yasa MD

  Dr. Moewardi General Hospital, Jebres, Surakarta, Central of Java, 57126

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized Controlled Trial and Double Blind (Researcher \& Patients)

Study Record Dates

• First Submitted: September 21, 2024
• First Posted: September 26, 2024
• Study Start: September 21, 2024
• Primary Completion: November 30, 2024
• Study Completion: December 7, 2024
• Last Updated: February 27, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)