Evaluation of Modified Antiplatelet Therapy with Prasugrel, Ticagrelor, and Acetylsalicylic Acid in Acute Myocardial Infarction Patients Post-Revascularization

The primary objective of this study is to evaluate a **modified Anti-Platelet Therapy** associated with low-dose rapamycin DES Firehawk in patients with **Acute Myocardial Infarction** who have undergone a complete revascularization strategy. The aim is to determine the therapy's effectiveness in achieving non-inferior NACCE (net adverse clinical and cerebral events) among clinically stable patients with low to moderate complexity acute myocardial infarction. This is clinically relevant as it may offer a safer alternative to current anti-platelet regimens, potentially reducing the risk of adverse events while maintaining therapeutic efficacy.

The secondary objective is to assess the same modified Anti-Platelet Therapy in conjunction with low-dose rapamycin DES Firehawk for its ability to reduce bleeding events in the same patient population. This evaluation is crucial for understanding the therapy's safety profile, particularly in terms of bleeding risk, which is a significant concern in the management of acute myocardial infarction patients.

The clinical trial involves participants diagnosed with **Acute Myocardial Infarction**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. The participants are clinically stable and exhibit low to moderate complexity in their acute myocardial infarction condition. The trial does not include a vulnerable population. The sponsor has not provided the total number of participants. Selection criteria for the trial population include individuals who are troponin-positive with Non-ST-Elevation Myocardial Infarction requiring early invasive treatment or ST-Elevation Myocardial Infarction requiring primary percutaneous coronary intervention (PCI), with PCI having occurred within the last 7 days. Participants must be eligible for per-protocol antiplatelet treatments and have provided written informed consent. The angiographic criteria specify successful revascularization in native coronary arteries with certain dimensional and procedural constraints. The trial does not focus on any specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate a modified **anti-platelet therapy** in patients with **acute myocardial infarction** who have undergone complete revascularization. This study employs a randomized, double-blind, controlled trial design to ensure the reliability and validity of the results. The trial is expected to last until April 2025, with participant recruitment having commenced in March 2021. The primary objective is to assess the non-inferiority of the modified therapy in achieving non-adverse clinical and cerebral events (NACCE) among clinically stable patients with low to moderate complexity acute myocardial infarction.

Participants will be involved in the study for a maximum treatment period of 52 weeks. The sequence of study visits includes an initial screening visit to confirm eligibility based on criteria such as troponin-positive non-ST-elevation myocardial infarction requiring early invasive treatment or ST-elevation myocardial infarction requiring primary percutaneous coronary intervention (PCI). Following successful revascularization, participants will be randomized to receive either the test or comparator treatments. Follow-up visits will be scheduled to monitor the participants' health status and adherence to the treatment protocol. The end-of-study visit will occur at 12 months post-index procedure to evaluate the primary and secondary endpoints, including NACCE and bleeding events as defined by the Bleeding Academic Research Consortium (BARC).

Participants may be withdrawn from the study if they experience significant adverse events, fail to adhere to the treatment protocol, or withdraw consent. The trial will utilize oral administration of the study drugs, which include prasugrel, ticagrelor, acetylsalicylic acid, and clopidogrel, all in the form of film-coated or gastro-resistant tablets. The study aims to provide valuable insights into the efficacy and safety of the modified anti-platelet therapy in the specified patient population.

The clinical trial involves the administration of **Efient** 10 mg film-coated tablets, which contain the active substance **prasugrel**. This medication is provided in the form of film-coated tablets and is administered orally. The maximum daily dose is 10 mg, with a total maximum dose of 520 mg over a treatment period of up to 52 weeks. The tablets are manufactured by SUBSTIPHARM and are not formulated for pediatric use. The chemical origin of the active substance is confirmed.

Another experimental treatment in the trial is **Brilique** 90 mg film-coated tablets, containing the active substance **ticagrelor**. These tablets are also administered orally, with a maximum daily dose of 180 mg and a total maximum dose of 9360 mg over a 52-week period. The manufacturer of Brilique is ASTRAZENECA AB, and the formulation is not intended for pediatric patients. The active substance is of chemical origin.

The comparator treatment in the study is **ASPIRINE PROTECT** 100 mg, which is a gastro-resistant tablet containing **acetylsalicylic acid**. This medication is administered orally, with a maximum daily dose of 75 mg and a total maximum dose of 3900 mg over the course of 52 weeks. The tablets are produced by BAYER HEALTHCARE and are chemically derived. This formulation is not designed for pediatric use.

Additionally, the trial includes **Plavix** 75 mg film-coated tablets, which contain the active substance **clopidogrel**. These tablets are administered orally, with a maximum daily dose of 75 mg and a total maximum dose of 3900 mg over a 52-week period. SANOFI WINTHROP INDUSTRIE is the manufacturer, and the active substance is of chemical origin. The formulation is not suitable for pediatric patients.

Efficacy in this clinical trial will be assessed primarily through the evaluation of **Net Adverse Clinical and Cerebral Events (NACCE)**. This composite endpoint includes all-cause death, non-fatal myocardial infarction, definite/probable stent thrombosis, stroke, or Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. The assessment will occur at 11 months post-randomization, which corresponds to 12 months following the index procedure. The primary objective is to determine if the modified Anti-Platelet Therapy, in conjunction with low-dose rapamycin DES Firehawk, is non-inferior in achieving these outcomes among clinically stable, low to moderate complexity acute myocardial infarction patients.

Secondary efficacy will be evaluated by monitoring BARC type 2, 3, or 5 bleeding events, also at 11 months post-randomization. The trial will involve the use of film-coated tablets containing active substances such as **prasugrel**, **ticagrelor**, **acetylsalicylic acid**, and **clopidogrel**, administered orally. The trial is designed to ensure complete revascularization in patients with acute myocardial infarction, with a focus on those who have undergone successful revascularization in native coronary arteries. The efficacy assessments will be conducted in accordance with the trial's protocol, ensuring rigorous data collection and analysis to support the study's objectives.