Dapagliflozin in STEMI Randomized Clinical Trial (DAPA STEMI)

THE UNIVERSITY of OTTAWA DAPAGLIFLOZIN in STEMI RANDOMIZED CLINICAL TRIAL

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Myocardial Infarction; ST Elevation Myocardial Infarction
• Intervention / Treatment: Drug: Dapagliflozin 10mg Tab; Diagnostic test: CMR

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 256
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Poppy MacPhee, BScN; Phone Number: 14646 6136967000; Email: pmacphee@ottawaheart.ca
• Study Contact Backup: Name: Tanya Abarbanel; Phone Number: 613-696-7000; Email: tabarbanel@ottawaheart.ca

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients referred for PPCI meeting the following criteria are eligible for the study:

1. Ischemic chest discomfort of ≥30 minutes duration, and
2. Onset of chest pain ≤12 hours prior to entry into the study, and

3. 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Dapagliflozin 10mg daily X 7 days	Drug: Dapagliflozin 10mg Tab; Dapagliflozin 10 mg daily X 7 days; Diagnostic test: CMR; CMR 3-5 days post randomization
Placebo Comparator: Placebo; Placebo daily X 7 days	Diagnostic test: CMR; CMR 3-5 days post randomization

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ottawa Heart Institute Research Corporation
• Investigators: Principal Investigator: Michel LeMay, MD, Ottawa Heart Institute Research Corporation

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: December 7, 2023
• First Submitted That Met QC Criteria: December 7, 2023
• First Posted (Actual): December 18, 2023

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: 20230332-01H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No