Comparison of Short-Term Versus 12-Month Dual Antiplatelet Therapy with Prasugrel and Acetylsalicylic Acid in Acute Coronary Syndrome Patients with Everolimus-Eluting Stents

The primary objective of this study is to evaluate the efficacy of short-term **antiplatelet therapy** compared to the standard guideline-recommended duration of dual antiplatelet therapy in patients with **acute coronary syndromes** who have been treated with an everolimus-eluting stent. The focus is on assessing the impact on bleeding and major adverse cardiovascular or cerebrovascular events. This is clinically relevant as optimizing the duration of antiplatelet therapy could potentially reduce bleeding risks while maintaining cardiovascular protection, thereby improving patient outcomes in this population.

The clinical trial involves participants diagnosed with **acute coronary syndromes** who have been treated with an everolimus-eluting stent. The study population includes both male and female subjects aged 18 years and older. The trial does not involve a vulnerable population. Participants were selected based on their ability to undergo randomization and receive prasugrel for a duration of 12 months. 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 selection criteria focus on the treatment with an everolimus-eluting stent and the capacity to adhere to the prescribed antiplatelet therapy regimen.

The clinical trial is designed to evaluate the efficacy and safety of short-term versus 12-month dual antiplatelet therapy in patients with **acute coronary syndromes** who have undergone percutaneous coronary intervention with everolimus-eluting stents. This is a randomized, double-blind, controlled trial, with participants being randomly assigned to receive either a short-term or a 12-month regimen of prasugrel plus **acetylsalicylic acid**. The trial is categorized as a phase 4 study, confirming the efficacy and safety of the investigational medicinal products in the specified setting. The estimated duration of the trial is from September 2024 to December 2028.

Participants will be involved in the study for a maximum of 11 months, with the possibility of early termination if they experience significant adverse events or if they are unable to comply with the study protocol. The sequence of study visits includes an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor safety and efficacy outcomes. The primary endpoints will be assessed between 1 and 12 months post-intervention, focusing on clinically relevant bleeding and major adverse cardiovascular or cerebrovascular events. Secondary endpoints include individual components of the primary endpoint, stent thrombosis rates, major bleeding, health-related quality of life, and angina status.

The clinical trial involves the administration of two **experimental medications**. The first medication is **Hjertemagnyl**, which contains the active substance **acetylsalicylic acid**. This medication is provided in the form of a **film-coated tablet** with a dosage strength of 75 mg. The route of administration is **oral**, and the maximum daily dose is 75 mg. The total maximum dose over the treatment period is 25,162 mg. The treatment duration is set for a maximum of 11 months. The medication is manufactured by Orifarm Healthcare A/S and is not a pediatric formulation. Compliance with the dosing schedule will be monitored throughout the trial.

The second medication used in the trial is **Prasugrel Krka**, which contains the active substance **prasugrel**. This medication is also provided as a **film-coated tablet** with a dosage strength of 10 mg. It is administered **orally**, with a maximum daily dose of 10 mg and a total maximum dose of 3,355 mg over the treatment period. The treatment duration is similarly set for a maximum of 11 months. This medication is produced by KRKA, D.D., Novo Mesto and is not intended for pediatric use. Participant adherence to the prescribed dosing regimen will be closely monitored during the study.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified for this trial. The primary objective of the study is to compare short-term antiplatelet therapy with the guideline-recommended dual antiplatelet therapy duration in patients with acute coronary syndromes treated with an everolimus-eluting stent, focusing on bleeding and major adverse cardiovascular or cerebrovascular events.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoints include the evaluation of clinically relevant bleeding, classified as BARC 2, 3, and 5, and the assessment of major adverse cardiovascular or cerebrovascular events (MACCE). These events are defined as a composite of cardiac death, myocardial infarction, definite stent thrombosis, ischemic stroke, or clinically driven target lesion revascularization. The effectiveness of the treatment will be measured for superiority in terms of bleeding and for non-inferiority concerning MACCE. These assessments will occur between 1 and 12 months following percutaneous coronary intervention (PCI).

Secondary endpoints will focus on the individual components of the primary endpoint, including the stent thrombosis rate as per the Academic Research Consortium-2 definition, major bleeding (BARC type 2, 3, and 5), health-related quality of life, and angina status based on the Canadian Cardiovascular Society classification system. The trial aims to compare short-term antiplatelet therapy with the guideline-recommended duration of dual antiplatelet therapy in patients with acute coronary syndromes treated with an everolimus-eluting stent. The trial is designed to confirm the efficacy and safety of the investigational medicinal product in this setting, as part of a phase 4 trial.