Clinical trial NCT06619600: Effect of Dapagliflozin in Myocardial Fibrosis and Ventricular Function in Patients With a ST-segment Elevation Myocardial Infarction
Official title: Effect of Dapagliflozin in Myocardial Fibrosis and Ventricular Function in Patients With a ST-segment Elevation Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: ST-segment Elevation Myocardial Infarction (STEMI)
Diabetes Mellitus
Heart Failure
Myocardial Fibrosis
Keywords: Dapagliflozin
Myocardial Fibrosis
ST-segment Elevation Myocardial Infarction (STEMI)
Cardiac Magnetic Resonance (CMR)
Heart Failure
Lead sponsor: Hospital Clinic of Barcelona
Sponsor class: OTHER
First posted: 2024-10-01
Enrollment: 54
Sex: ALL
Minimum age (years): 30
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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\&amp;#39;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.

Eligibility criteria: 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.

Primary outcomes:
measure: Extracellular volume (ECV, %)
timeFrame: 6 months
Secondary outcomes:
measure: Serum levels of C-terminal propeptide of type I procollagen (PICP)
timeFrame: 6 months
measure: N-terminal propeptide of type III (PIIINP)
timeFrame: 6 months
measure: Galectin-3 procollagen (Gal-3)
timeFrame: 6 months
measure: High-Sensitivity cardiac Troponin I (hs-cTnI)
timeFrame: 6 months
Other outcomes:
measure: N-terminal pro-brain natriuretic peptide (NT-proBNP)
timeFrame: 6 months
measure: Soluble suppression of tumorigenicity 2 (sST2)
timeFrame: 6 months
measure: Indexed ventricular mass of the left ventricle (LVMI, g/m^2)
timeFrame: 6 months
measure: Indexed End-diastolic volume of the left ventricle (LVEDVI, mL/m^2)
timeFrame: 6 months
measure: Indexed End-systolic volume of the left ventricle (LVESVI, mL/m^2)
timeFrame: 6 months
measure: Left ventricular ejection fraction (LVEF, %)
timeFrame: 6 months
measure: Body weight (BW, Kgs)
timeFrame: 6 months
measure: Major Adverse Cardiovascular Events (MACE)
timeFrame: 6 months
measure: Hospitalizations for Heart Failure (HHF)
timeFrame: 6 months
Locations:
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
state: Catalonia
city: Barcelona
country: Spain
facility: Hospital Clinic of Barcelona
state: Catalonia
Study officials:
affiliation: Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA.
name: Luis Ortega, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clínic, Cardiovascular Clinic Institute, Institut d&#39;Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
name: Salvatore Brugaletta, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.