Efficacy of Dapagliflozin on Cardiac Systolic Function and Remodeling in Acute Myocardial Infarction Patients with Left Ventricular Dysfunction

The primary objective of the study is to assess the **efficacy** of dapagliflozin, in addition to standard recommended therapy, compared to standard recommended therapy alone (i.e., with placebo) on cardiac systolic function and remodeling at 6 months from randomization by transthoracic echocardiography (TTE) in patients with acute myocardial infarction (AMI) and left ventricular (LV) dysfunction. This is clinically relevant as it aims to determine whether dapagliflozin can improve cardiac function and structure, potentially reducing the risk of cardiac failure in this patient population.

Secondary objectives include evaluating the efficacy and safety of dapagliflozin compared to placebo in addition to optimal secondary prevention in preventing cardiac dysfunction after AMI with LV dysfunction. This will be assessed through changes in several parameters from baseline to Month 6 (+4 weeks), including pulmonary congestion by TTE, clinical outcomes, biomarkers, and severe complications related to dapagliflozin. Additionally, cardiac remodeling will be assessed by TTE using changes in cardiac volumes and strain.

The clinical trial focuses on patients diagnosed with **cardiac failure**, specifically targeting those with left ventricular (LV) dysfunction following an acute myocardial infarction (AMI). The study population includes both male and female participants aged 18 years and older. Participants are required to have a systolic blood pressure greater than 100 mmHg and/or a diastolic blood pressure greater than 70 mmHg before the first dosing. The trial does not include a vulnerable population. Participants must be affiliated with a national healthcare system, excluding those under AME. The sponsor has not provided the total number of participants involved in the study. The selection criteria emphasize the inclusion of individuals who have undergone percutaneous coronary intervention (PCI) or angiography procedures and have an estimated glomerular filtration rate (eGFR) of at least 25 mL/min per 1.73m². The trial does not specify any particular lifestyle considerations such as diet or physical activity. Participants must be capable of providing written informed consent and commit to a 6-month follow-up period.

The clinical trial is designed to evaluate the efficacy of **dapagliflozin** in addition to standard recommended therapy compared to standard therapy alone, using a **randomized**, **double-blind**, and **controlled** methodology. The trial aims to assess the impact on cardiac systolic function and remodeling in patients with acute myocardial infarction (AMI) and left ventricular (LV) dysfunction. The study will span approximately 6 months from the date of randomization, with the primary endpoints being changes in left ventricular ejection fraction (LVEF) and left atrium volume (LAV) as measured by transthoracic echocardiography (TTE).

Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, medical history, and ability to provide informed consent. Following randomization, participants will receive either dapagliflozin or a placebo, administered orally. Follow-up visits will occur periodically to monitor the participants' health status, adherence to the treatment regimen, and any adverse events. The end-of-study visit will take place at the conclusion of the 6-month period, where final assessments will be conducted to evaluate the primary and secondary endpoints.

The expected length of participant involvement is approximately 6 months, with conditions for early termination including significant adverse events, withdrawal of consent, or non-compliance with the study protocol. Secondary endpoints will include changes in left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and other cardiac parameters, as well as the duration of hospital stay, all-cause mortality, and cardiovascular outcomes. The trial will also monitor adverse events related to dapagliflozin, such as volume depletion and renal function changes, to ensure participant safety throughout the study duration.

The clinical trial involves the administration of **Dapagliflozin**, a pharmaceutical agent classified as a **film-coated tablet**. The active substance, **Dapagliflozin**, is of chemical origin and is administered orally. The dosage is set at 10 mg per day, with a maximum total dose of 1825 mg over the course of the study. The treatment period is defined as 6 months, during which the efficacy of Dapagliflozin in addition to standard recommended therapy will be assessed. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in this study. The placebo is designed to mimic the appearance and administration route of the Dapagliflozin tablet, ensuring blinding of the participants and investigators. The placebo is administered orally at a frequency matching that of the active treatment, maintaining the integrity of the study design. The use of a placebo allows for the evaluation of Dapagliflozin's efficacy in comparison to standard recommended therapy alone. Compliance with placebo administration will be similarly monitored to maintain consistency across the study arms.

The efficacy of dapagliflozin in the clinical trial titled "DAPAgliflozine to attenuate cardiac RemOdeling afTEr aCuTe myocardial infarction (DAPA-PROTECTOR)" will be assessed through several primary and secondary endpoints. The primary endpoints focus on evaluating two independent predictors of mortality after acute myocardial infarction (AMI): cardiac systolic function and remodeling. Cardiac systolic function will be assessed by the change in left ventricular ejection fraction (LVEF) from baseline to Month 6 (+4 weeks) using transthoracic echocardiography (TTE). Remodeling will be evaluated by the change in left atrium volume (LAV) over the same period, also using TTE.

Secondary endpoints include a comparison of changes from baseline to Month 6 (+4 weeks) in left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), left ventricular global longitudinal strain (LS), and left atrial strain (LAS) using TTE. Additional secondary endpoints involve comparisons between the experimental and placebo groups regarding the duration of hospital stay, all-cause mortality at 6 months, cardiovascular death or worsening heart failure at 6 months, and the number of re-admissions due to heart failure at 6 months. Changes in pulmonary congestion, plasma levels of NT-pro BNP and HBA1C, and body weight from baseline to Month 6 (+4 weeks) will also be measured. Adverse events, particularly those potentially related to dapagliflozin complications, will be monitored at Month 6.