Efficacy and Safety of Acetylsalicylic Acid Versus Acetylsalicylic Acid and Fondaparinux Sodium in Non-ST-Elevation Myocardial Infarction Patients

The primary objective of this study is to compare the **efficacy** of treatment with aspirin alone versus combination therapy with fondaparinux and aspirin prior to an early invasive strategy in patients with Non-ST-Elevation Myocardial Infarction (**NSTEMI**). This comparison is clinically relevant as it aims to determine the optimal therapeutic approach to improve patient outcomes in NSTEMI, a condition characterized by partial blockage of blood flow to the heart, which can lead to significant morbidity and mortality.

Secondary objectives include evaluating and comparing the relative **bleeding risk** associated with the use of aspirin alone and in combination with fondaparinux prior to an invasive strategy in patients with NSTEMI. Understanding the bleeding risk is crucial for balancing the benefits of antithrombotic therapy with its potential adverse effects, thereby guiding clinical decision-making in the management of NSTEMI.

The clinical trial involves participants diagnosed with **Non-ST-Elevation Myocardial Infarction (NSTEMI)**. The study population includes both male and female subjects, with an age range starting from 18 years and above. Participants are required to have a verified diagnosis of NSTEMI, characterized by a rise or fall in cardiac troponin levels, symptoms of acute ischemia, or ECG changes compatible with acute ischemia. The trial does not include vulnerable populations, and participants must have an expected remaining lifespan of more than one year, as well as the independent capacity to provide informed consent. The sponsor has not provided information regarding the total number of participants. The selection criteria ensure that individuals are capable of understanding and consenting to the study, and no specific lifestyle considerations such as diet or physical activity are highlighted as part of the trial requirements.

The clinical trial is designed to evaluate the **efficacy** and safety of **acetylsalicylic acid** alone versus a combination therapy of **acetylsalicylic acid** and **fondaparinux sodium** in patients diagnosed with Non-ST-Elevation Myocardial Infarction (NSTEMI). This study is structured as a randomized, double-blind, controlled trial, ensuring that neither the participants nor the investigators are aware of the treatment allocations, thereby minimizing bias. The trial is expected to commence on January 1, 2025, and conclude by July 1, 2027, with an estimated duration of 2.5 years.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a verified diagnosis of NSTEMI, age over 18 years, and an expected lifespan exceeding one year. Following randomization, participants will receive either the test or control treatment. The trial includes follow-up visits to monitor the primary endpoint, which is a composite of 30-day mortality, new myocardial infarction, and refractory ischemia necessitating acute coronary angiography before the scheduled time. Secondary endpoints include the occurrence of death or new myocardial infarction over various timeframes, incidence of cerebrovascular accidents within 30 days, length of hospital stay, and left ventricular ejection fraction at discharge.

The expected length of participant involvement is approximately one year, with conditions for early termination including withdrawal of consent, adverse events, or any situation where continued participation is deemed unsafe by the investigator. The trial aims to provide valuable insights into the comparative benefits of the treatment regimens, adhering strictly to current guidelines for the use and dosing of the medications involved.

The clinical trial involves the administration of **acetylsalicylic acid**, a synthetic non-steroidal anti-inflammatory drug, in the form of a film-coated tablet. The dosage for this medication is set at a maximum daily dose of 300 mg, with a total maximum dose of 750 mg over the treatment period. The route of administration is oral, and the treatment period is limited to one day. This medication is not a pediatric formulation and is used as a standard-of-care therapy in the study.

**Fondaparinux sodium** is also utilized in this clinical trial as a synthetic, selective inhibitor of Factor Xa. It is provided as a solution for injection, administered via subcutaneous injection. The trial includes two dosing regimens for fondaparinux sodium. The first regimen involves a maximum daily dose of 1.5 mg, with a total maximum dose of 10.5 mg over the treatment period. The second regimen allows for a maximum daily dose of 2.5 mg, with a total maximum dose of 17.5 mg. Both regimens are administered over a one-day treatment period. The reduced dose of fondaparinux sodium is specifically used for patients with an estimated glomerular filtration rate (eGFR) of 20-50 ml/min. This medication is not a pediatric formulation and serves as a comparator treatment in the study.

The clinical trial aims to assess the efficacy of **acetylsalicylic acid** alone versus a combination therapy of **fondaparinux sodium** and **acetylsalicylic acid** in patients with Non-ST-Elevation Myocardial Infarction (NSTEMI) prior to an early invasive strategy. Efficacy will be evaluated using both primary and secondary endpoints. The primary endpoint is a composite measure that includes 30-day mortality, 30-day new myocardial infarction (MI), and refractory ischemia leading to acute coronary angiography (CAG) before it is scheduled. Secondary endpoints include a composite of death or new MI occurrences within 180 days, 1 year, 3 years, 5 years, and 10 years, incidence of cerebrovascular accidents (CVA) within 30 days, including ischemic stroke and transient ischemic attack (TIA), length of hospital stay, and left ventricular ejection fraction (LVEF) at discharge.

The trial will follow a structured schedule for measuring and collecting data on these endpoints. The primary endpoint will be assessed at the 30-day mark, while secondary endpoints will be evaluated at multiple timepoints, including 180 days, 1 year, 3 years, 5 years, and 10 years. The trial is designed to ensure that the use and doses of the medications strictly adhere to current guidelines, as both fondaparinux and aspirin are approved treatments for NSTEMI. The trial is categorized as low intervention, focusing on the evaluation of efficacy and safety of these already approved medications.