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

Phase 4

Completed

• Conditions: Acute Myocardial Infarction (AMI); STEMI - ST Elevation Myocardial Infarction (MI); NSTEMI - Non-ST Segment Elevation Myocardial Infarction (MI)
• Interventions: 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

• Registration Number: NCT06615674
• Lead Sponsor: Yoga Yudhistira

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.

Detailed Description

The study is a randomized controlled trial, single-center study in Acute Myocardial Infarction (AMI) patients held in Moewardi General Hospital, Central Java, Indonesia. The investigator divided 40 patients with AMI into two groups, the first is the Dapagliflozin group, which will get 10mg of Dapagliflozin once a day every morning and the second group will have a placebo once a day every morning also for 14 days. Each patient will be checked for Caspase-3 level from blood serum as primary outcome and Global Work (GW) echocardiographic parameters such as GWI, GCW, GWW, and GWE as secondary outcome at admission and 14 days after intervention. The study was approved by the hospital ethics committee. The clinical parameters above will then be analyzed. To determine the mean difference between unpaired groups (treatment and control), an independent T-test is used if the distribution is normal (if not, the Mann-Whitney test is used). Normality testing is performed using the Shapiro-Wilk test, considering the sample size is less than 50.

Study Timeline

• Study Start: 2024-09-21
• Study First Submitted: 2024-09-21
• Study First Submitted QC: 2024-09-24
• Study First Posted: 2024-09-26
• Primary Completion: 2024-11-30
• Study Completion: 2024-12-07
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-24
• Last Update Posted: 2025-02-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. 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.
2. Aged 18-75 years
3. Willing to participate in the study and sign informed consent.

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dapagliflozin	Forxiga® 10 mg Film-Coated Tablet, manufactured by AstraZeneca Pharmaceuticals LP, USA for AstraZeneca Pharmaceuticals Co. Ltd., China imported by PT AstraZeneca Indonesia, Indonesia	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
Control	Forxiga® 10 mg Film-Coated Tablet, manufactured by AstraZeneca Pharmaceuticals LP, USA for AstraZeneca Pharmaceuticals Co. Ltd., China imported by PT AstraZeneca Indonesia, Indonesia	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.

Primary Outcome Measures

Name	Time	Method
Change in Biomolecular Parameters	14 days	Change in Caspase-3 (ng/L) level in blood serum patients

Secondary Outcome Measures

Name	Time	Method
Change in Echocardiographic Parameters	14 days	Change in Global Work Index (GWI) (mmHg%), Global Constructive Work (GCW) (mmHg%), Global Wasted Work (GWW) (mmHg%), Global Work Efficiency (GWE) (%) parameter from patients

Trial Locations

Locations (1)

Dr. Moewardi General Hospital, Jebres, Surakarta, Central of Java, 57126; 🇮🇩 Surakarta, Central of Java, Indonesia