Dapagliflozin in STEMI Randomized Clinical Trial

Study Overview
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Brief Summary
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The goal of this clinical trial is to assess the safety and efficacy of SGLT2i in limiting infarct size in patients with STEMI referred for PPCI. Eligible STEMI patients enrolled into the trial will be randomized to a SGLT2i or placebo. Cardiovascular Magnetic Resonance (CMR) imaging will be used to determine the infarct size.

Detailed Description
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DAPA STEMI is a single center, randomized, double-blind, parallel group study in which eligible participants with a STEMI and undergoing PPCI will be recruited and randomly assigned to dapagliflozin or placebo to take for 7 days. Participants will be prescribed study treatment i.e. dapagliflozin (10 mg) or placebo daily for 7 days. A CMR will be obtained at day 3-5 to assess for infarct size. Participants will have follow-up visits at 30, 90, and 180 days to assess for cardiovascular events.

Official Title
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THE UNIVERSITY of OTTAWA DAPAGLIFLOZIN in STEMI RANDOMIZED CLINICAL TRIAL

Conditions
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ST Elevation Myocardial Infarction, Myocardial Infarction

Intervention / Treatment
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* Drug: Dapagliflozin 10mg Tab
* Diagnostic Test: CMR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients referred for PPCI meeting the following criteria are eligible for the study: Ischemic chest discomfort of ≥30 minutes duration, and Onset of chest pain ≤12 hours prior to entry into the study, and One of the following High-Risk criteria on a standard 12 lead ECG: a. Anterior STEMI with ST-segment elevation ≥2mm (0.2 mV) in each of at least 2 contiguous precordial leads (V1-V6) b. Extensive non-anterior STEMI defined as ST-segment elevation of >1mm in two or more contiguous non-anterior leads accompanied by i. 8 or more leads with > 1 mm ST elevation or depression, or both; OR ii. Sum of ST- segment elevation >20mm Exclusion Criteria: 1. Age < 18 years 2. Any contraindication to undergo CMR imaging 3. Killip 4 (Cardiogenic shock on presentation) 4. Therapy with SGLT2i within last 8 weeks 5. Type 1 diabetes mellitus 6. Pregnancy 7. Nursing mother 8. Unwilling to use appropriate forms of contraception, as applicable 9. Chronic symptomatic HF with prior hospitalization for HF within the last year 10. Known LVEF <40% by any prior measure, documented before the current MI hospitalization 11. Known history of prior MI 12. Any non-CV condition with a life expectancy of less than one year 13. Previous randomization in the present study 14. Participation in a study with another investigational device or drug < four weeks 15. Inability to provide informed consent 16. Confirmed ketoacidosis at time of admission 17. Known severe hepatic impairment (Cirrhosis) 18. Severe renal impairment (eGFR < 30 mL/min1.73m2 (based on prior or baseline blood work) 19. Known severe valvular heart disease 20. Need for CABG within 90 days based on the results of the initial coronary angiogram 21. False positive STEMI (based on the results of the coronary angiogram)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: a single center, randomized, double-blind, parallel group study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Dapagliflozin 10mg daily X 7 days | Drug: Dapagliflozin 10mg Tab<br>* Dapagliflozin 10 mg daily X 7 days<br>Diagnostic Test: CMR<br>* CMR 3-5 days post randomization<br>|
| Placebo Comparator: Placebo<br>Placebo daily X 7 days | Diagnostic Test: CMR<br>* CMR 3-5 days post randomization<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infarct Size | Infarct size (% of total LV mass) measured by CMR | 3-5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multiple Cardiac Adverse Events (MACE) | A composite of death, reinfarction, stroke, or rehospitalization for HF | 3 months, and 6 months | 
| Cardiogenic Shock | Evaluated using the SCAI classification; only class C, D, or E will be adjudicated as a secondary outcome | during initial hospitalization | 
| Acute Kidney Injury | As defined according to the KDIGO definition | 3 months, and 6 months |