Evaluation of Immediate Versus Delayed Administration of Bisoprolol, Ramipril, and Dapagliflozin in Patients with ST-Elevation Myocardial Infarction

The primary objective of the STAMI-BAS trial is to evaluate the effect of immediate versus delayed administration of **beta blockers**, **angiotensin converting enzyme inhibitors (ACEI)**, and **sodium/glucose cotransporter 2 (SGLT2) inhibitors** on echocardiographic parameters and biomarkers in patients with **ST-elevation myocardial infarction (STEMI)**. This is clinically relevant as optimizing the timing of these medications could potentially improve cardiac function and patient outcomes following a myocardial infarction.

The clinical trial involves participants diagnosed with **ST-elevation myocardial infarction (STEMI)**, a condition characterized by a significant blockage of blood flow to the heart. The study population includes both male and female subjects, with an age range that spans from young adults to older adults. The trial does not focus on a vulnerable population. Participants were selected based on their medical condition, specifically those who have undergone primary percutaneous coronary intervention (PCI) within six hours of symptom onset, excluding prodromal symptoms. Informed consent was a prerequisite for inclusion. The sponsor has not provided information regarding the total number of participants. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The study aims to assess the impact of immediate versus delayed administration of specific medications on echocardiographic parameters and biomarkers in the target population.

The clinical trial is designed to evaluate the effects of immediate versus delayed administration of **beta blockers**, **angiotensin converting enzyme inhibitors (ACEI)**, and **sodium/glucose cotransporter 2 (SGLT2) inhibitors** on echocardiographic parameters and biomarkers in patients with ST-elevation myocardial infarction (STEMI). This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know which treatment the participants are receiving, thereby minimizing bias. The trial is expected to commence recruitment on June 30, 2024, and conclude by December 31, 2027, with an estimated duration of participant involvement being one month.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as undergoing primary percutaneous coronary intervention (PCI) within six hours of symptom onset and providing informed consent. Following the screening, participants will be randomized to receive either immediate or delayed treatment with the investigational drugs. The primary endpoint will be assessed by measuring the global longitudinal strain (GLS) at day 7, adjusted for baseline GLS. Secondary endpoints include left ventricular ejection fraction (LVEF), NT-proBNP levels, and cardiac troponin levels, with assessments conducted at various intervals, including day 7 and day 30 post-PCI.

Follow-up visits will be scheduled to monitor the participants' response to the treatment and to collect data on the primary and secondary endpoints. The end-of-study visit will occur at the conclusion of the treatment period, where final assessments will be made, including the evaluation of infarct size using cardiac magnetic resonance imaging (CMRI) at 30 days. Participants may be withdrawn from the study early if they experience adverse effects, fail to comply with the study protocol, or withdraw consent. The trial aims to provide valuable insights into the optimal timing of drug administration in the management of STEMI, potentially influencing future treatment guidelines.

The clinical trial involves the administration of three experimental medications: **Ramipril**, **Bisoprolol**, and **Dapagliflozin**. Each medication is administered in the form of a tablet, with a maximum daily dose of 10 mg and a total maximum dose of 300 mg over the treatment period. The treatment period for each medication is limited to one month. All medications are administered orally.

**Ramipril** is provided in tablet form and is a chemical substance used as an angiotensin-converting enzyme inhibitor. The administration of Ramipril is conducted orally, with a maximum daily dose of 10 mg. The total dose over the treatment period should not exceed 300 mg. Compliance with the dosing schedule is monitored to ensure adherence to the protocol.

**Bisoprolol** is administered as a film-coated tablet. It is a beta-blocker, also of chemical origin, and is given orally. The maximum daily dose is set at 10 mg, with a total maximum dose of 300 mg for the duration of the study. Participant compliance is monitored to ensure the correct dosing schedule is followed.

**Dapagliflozin** is also administered as a film-coated tablet. It functions as a sodium-glucose cotransporter 2 inhibitor and is administered orally. The dosing schedule allows for a maximum daily dose of 10 mg, with a total maximum dose of 300 mg over the treatment period. Monitoring of participant compliance is conducted to ensure adherence to the prescribed dosing regimen.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in this trial. The focus is on the immediate versus late administration of the experimental medications to assess their effects on echocardiographic parameters and biomarkers in subjects with ST-elevation myocardial infarction.

The efficacy of the clinical trial titled "STunning in Acute Myocardial Infarction – Beta blockers, Angiotensin converting enzyme inhibitors and Sodium/glucose cotransporter 2 inhibitors trial (STAMI-BAS)" will be assessed using specific primary and secondary endpoints. The primary endpoint is the **Global Longitudinal Strain (GLS)** percentage at day 7 ± 24 hours after percutaneous coronary intervention (PCI), adjusted for baseline GLS measured on day 0. Secondary endpoints include the left ventricular ejection fraction (LVEF), adjusted for baseline LVEF, and NT-proBNP levels on day 7, adjusted for baseline NT-proBNP. Additionally, the area under the curve (AUC) of cardiac troponin-T and cardiac troponin-I will be evaluated at day 30, along with infarct size at 30 days, assessed by cardiac magnetic resonance imaging (CMRI).

The trial aims to examine the effect of immediate versus late administration of beta blockers, angiotensin converting enzyme inhibitors (ACEI), and sodium/glucose cotransporter 2 (SGLT2) inhibitors on echocardiographic parameters and biomarkers in subjects with ST-elevation myocardial infarction (STEMI). The efficacy parameters will be collected and analyzed at specified timepoints, including day 7 and day 30, using validated laboratory tests and imaging techniques. The trial is designed to ensure that all investigational medicinal products are used in accordance with current European Society of Cardiology treatment guidelines, and the study is categorized as low intervention.