Effect of Dapagliflozin in Myocardial Fibrosis and Ventricular Function in Patients with a ST-segment Elevation Myocardial Infarction (DAPA-STEMI)

The DAPA-STEMI trial investigates whether dapagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), reduces heart muscle scarring (fibrosis) and improves heart function after a ST-segment elevation myocardial infarction (STEMI). The trial will use cardiac MRI to measure changes in heart structure and function over six months. Patients aged 30-85 who have had a recent STEMI will receive either dapagliflozin or a placebo. The study aims to provide mechanistic insights into heart failure prevention after heart attacks.

Study Overview

• Status: Active, not recruiting
• Conditions: Myocardial Fibrosis; Heart Failure; Diabetes Mellitus; ST-segment Elevation Myocardial Infarction (STEMI)
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Placebo

Detailed Description

The DAPA-STEMI trial is a clinical research study designed to investigate whether dapagliflozin, a medication known as a sodium-glucose cotransporter 2 inhibitor (SGLT2i), can reduce the extent of heart muscle damage and improve heart function in patients who have experienced a heart attack. Specifically, the study focuses on patients who have had a type of heart attack known as a ST-segment elevation myocardial infarction (STEMI), which is a serious condition that often leads to long-term heart damage and heart failure.

The study aims to answer whether treatment with dapagliflozin can reduce the amount of scarring (fibrosis) that develops in the heart after a heart attack, and whether this reduction in scarring improves the overall function of the heart. Scarring in the heart can lead to stiffening of the heart muscle, which affects its ability to pump blood effectively and can result in heart failure. By using advanced imaging techniques, such as cardiac magnetic resonance imaging (MRI), the study will measure changes in the heart's structure and function over time.

The primary question the study seeks to answer is whether dapagliflozin can decrease the amount of heart muscle scarring (fibrosis) and improve heart function when compared to a placebo (an inactive treatment). The study will also examine whether dapagliflozin affects other important heart health markers, such as blood levels of proteins that indicate heart muscle damage and the overall size and function of the heart chambers.

The study will enroll patients aged 30 to 85 who have recently experienced a STEMI and undergone successful treatment to open the blocked artery. Participants will be randomly assigned to receive either dapagliflozin or a placebo for six months, and their heart function and scarring will be monitored through imaging and blood tests during that time.

The results of this study may provide important insights into new ways to protect the heart after a heart attack and prevent the development of heart failure, offering potential benefits to a wide range of patients who experience heart attacks.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Catalonia
    • Barcelona, Catalonia, Spain, 08036
      • Hospital Clinic of Barcelona
    • Barcelona, Catalonia, Spain, 08025
      • Hospital De La Santa Creu I Sant Pau

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients between 30 - 85 years of age.
2. Patients with first infarction with ST-segment elevation documented in an ambulance or a cardiac catheterization laboratory (ST-segment elevation ≥2 mm in at least two contiguous leads) less than 12 hours after onset of symptoms that last ≥ 20 min, that is treated with primary percutaneous cardiac intervention.
3. The target lesion must be a de novo lesion located in a native vessel.
4. The patient understands and accepts the clinical monitoring and cardiac magnetic resonance.
5. The patient has to be hemodynamically stable (Killip classification 1) at the time of the initial cardiac magnetic resonance.
6. A left ventricular ejection fraction ≤50% in the baseline echocardiogram.

Exclusion Criteria:

1. Pregnant or lactating women.
2. Type 1 diabetes.
3. Previous treatment with SGLT2i.
4. Severe liver disease (Child-Pugh C).
5. Kidney disease defined as stage III or worse (eGFR less than 45 ml/min).
6. Systolic blood pressure less than 90 mmHg at the screening visit.
7. Malignancy (receiving active treatment) or other life-threatening diseases.
8. Any contraindication to cardiac MRI (e.g., claustrophobia, metal implants, penetrating eye injury, or exposure to metal fragments in the eye that require medical attention).
9. Previous complicated urinary tract infection in men or repeated urinary infection in women.
10. Patients treated with fibrinolytic therapy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matched placebo qd	Drug: Placebo; Matched placebo qd
Experimental: Dapagliflozin; Dapagliflozin 10 mg qd	Drug: Dapagliflozin; Dapagliflozin 10 mg qd

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extracellular volume (ECV, %)	To determine the effect of dapagliflozin compared with placebo in the change (Δ) of the extracellular volume (ECV) of the remote myocardium between the 6-month and baseline follow- up, evaluated by cardiac magnetic resonance (ΔECV dapagliflozin group versus ΔECV placebo group; [ΔECV = ECV 6-month - ECV baseline]).	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum levels of C-terminal propeptide of type I procollagen (PICP)	To determine the effect of dapagliflozin compared with placebo in the change (Δ) of the serum levels of C-terminal propeptide of type I procollagen (PICP) between the 6-month and baseline follow- up (ΔPICP dapagliflozin group versus ΔPICP placebo group; [ΔPICP = PICP 6-month - PICP baseline]).	6 months
N-terminal propeptide of type III (PIIINP)	To determine the effect of dapagliflozin compared with placebo in the change (Δ) of the serum levels of N-terminal propeptide of type III (PIIINP) between the 6-month and baseline follow- up (ΔPIIINP dapagliflozin group versus ΔPIIINP placebo group; [ΔPIIINP = PIIINP 6-month - PIIINP baseline]).	6 months
Galectin-3 procollagen (Gal-3)	To determine the effect of dapagliflozin compared with placebo in the change (Δ) of the serum levels of galectin-3 procollagen (Gal-3) between the 6-month and baseline follow- up (ΔGal-3 dapagliflozin group versus ΔGal-3 placebo group; [ΔGal-3 = Gal-3 6-month - Gal-3 baseline]).	6 months
High-Sensitivity cardiac Troponin I (hs-cTnI)	To determine the effect of dapagliflozin compared with placebo in the change (Δ) of the serum levels of High-Sensitivity cardiac Troponin I (hs-cTnI) between the 6-month and baseline follow- up (hs-cTnI dapagliflozin group versus hs-cTnI placebo group; [Δhs-cTnI = hs-cTnI 6-month - hs-cTnI baseline]).	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Indexed ventricular mass of the left ventricle (LVMI, g/m^2)	To determine the effect of dapagliflozin compared with placebo in the change (Δ) of the Indexed ventricular mass of the left ventricle (LVMI) between the 6-month and baseline follow- up, evaluated by cardiac magnetic resonance (ΔLVMI dapagliflozin group versus ΔLVMI placebo group; [ΔLVMI = LVMI 6-month - LVMI baseline]).	6 months
Indexed End-diastolic volume of the left ventricle (LVEDVI, mL/m^2)	To determine the effect of dapagliflozin compared with placebo in the change (Δ) of the Indexed End-diastolic volume of the left ventricle (LVEDVI) between the 6-month and baseline follow- up, evaluated by cardiac magnetic resonance (ΔLVEDVI dapagliflozin group versus ΔLVEDVI placebo group; [ΔLVEDVI = LVEDVI 6-month - LVEDVI baseline]).	6 months
Indexed End-systolic volume of the left ventricle (LVESVI, mL/m^2)	To determine the effect of dapagliflozin compared with placebo in the change (Δ) of the Indexed End-systolic volume of the left ventricle (LVESVI) between the 6-month and baseline follow- up, evaluated by cardiac magnetic resonance (ΔLVESVI dapagliflozin group versus ΔLVESVI placebo group; [ΔLVESVI = LVESVI 6-month - LVESVI baseline]).	6 months
Left ventricular ejection fraction (LVEF, %)	To determine the effect of dapagliflozin compared with placebo in the change (Δ) of the Left ventricular ejection fraction (LVEF) between the 6-month and baseline follow- up, evaluated by cardiac magnetic resonance (ΔLVEF dapagliflozin group versus ΔLVEF placebo group; [ΔLVEF = LVEF 6-month - LVEF baseline]).	6 months
Body weight (BW, Kgs)	To determine the effect of dapagliflozin compared with placebo in the change (Δ) of the Body weight (BW) between the 6-month and baseline follow- up, (ΔBW dapagliflozin group versus ΔBW placebo group; [ΔBW = BW 6-month - BW baseline]).	6 months
Major Adverse Cardiovascular Events (MACE)	Difference in the incidence of Major Adverse Cardiovascular Events (MACE), defined as a composite of death, non-fatal myocardial infarction, and non-fatal stroke, between the dapagliflozin and placebo groups.	6 months
Hospitalizations for Heart Failure (HHF)	Difference in the incidence of Hospitalizations for Heart Failure (HHF) between the dapagliflozin and placebo groups.	6 months
N-terminal pro-brain natriuretic peptide (NT-proBNP)	To determine the effect of dapagliflozin compared with placebo in the change (Δ) of the serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) between the 6-month and baseline follow- up (NT-proBNP dapagliflozin group versus NT-proBNP placebo group; [ΔNT-proBNP = NT-proBNP 6-month - NT-proBNP baseline]).	6 months
Soluble suppression of tumorigenicity 2 (sST2)	To determine the effect of dapagliflozin compared with placebo in the change (Δ) of the serum levels of Soluble suppression of tumorigenicity 2 (sST2) between the 6-month and baseline follow- up (sST2 dapagliflozin group versus sST2 placebo group; [ΔsST2 = sST2 6-month - sST2 baseline]).	6 months

Collaborators and Investigators

• Sponsor: Hospital Clinic of Barcelona
• Investigators: Principal Investigator: Luis Ortega, MD, PhD, Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA.; Study Chair: Salvatore Brugaletta, MD, PhD, Hospital Clínic, Cardiovascular Clinic Institute, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

Publications and helpful links

General Publications

• Perea RJ, Morales-Ruiz M, Ortiz-Perez JT, Bosch X, Andreu D, Borras R, Acosta J, Penela D, Prat-Gonzalez S, de Caralt TM, Martinez M, Morales-Romero B, Lasalvia L, Donnelly J, Jimenez W, Mira A, Mont L, Berruezo A. Utility of galectin-3 in predicting post-infarct remodeling after acute myocardial infarction based on extracellular volume fraction mapping. Int J Cardiol. 2016 Nov 15;223:458-464. doi: 10.1016/j.ijcard.2016.08.070. Epub 2016 Aug 8.
• Ortega-Paz L, Cristobal H, Ortiz-Perez JT, Garcia de Frutos P, Mendieta G, Sandoval E, Rodriguez JJ, Ortega E, Garcia-Alvarez A, Brugaletta S, Sabate M, Dantas AP. Direct actions of dapagliflozin and interactions with LCZ696 and spironolactone on cardiac fibroblasts of patients with heart failure and reduced ejection fraction. ESC Heart Fail. 2023 Feb;10(1):453-464. doi: 10.1002/ehf2.14186. Epub 2022 Oct 27.

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2021
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: September 27, 2024
• First Submitted That Met QC Criteria: September 27, 2024
• First Posted (Actual): October 1, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 17, 2025
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Heart Failure; Dapagliflozin; Myocardial Fibrosis; Cardiac Magnetic Resonance (CMR); ST-segment Elevation Myocardial Infarction (STEMI)
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Necrosis; Myocardial Ischemia; Ischemia; ST Elevation Myocardial Infarction; Heart Failure; Fibrosis; Myocardial Infarction; Infarction; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Dapagliflozin
• Other Study ID Numbers: ESR-19-14489; 2018-003105-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: To be discussed.

Drug and device information, study documents

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