Evaluation of Biomarker-Driven Intensification of Cardiovascular Risk Management in Patients with High Risk for Recurrent Events Using Icosapent Ethyl and Drug Combination

The primary objective of this randomized controlled trial is to evaluate the **efficacy** of intensified residual risk management compared to standard guideline treatment in patients with high risk for recurrent cardiovascular events, specifically focusing on a composite effect. This is clinically relevant as it aims to improve outcomes in patients who have experienced an **acute myocardial infarction**, a condition associated with significant morbidity and mortality. The study seeks to determine whether a more aggressive management approach can reduce the risk of subsequent cardiovascular events.

Secondary objectives include evaluating the efficacy of intensified residual risk management versus standard guideline treatment in terms of individual components of the primary composite endpoint and other cardiovascular endpoints. This will provide a more detailed understanding of how intensified management impacts various aspects of cardiovascular health, potentially guiding future treatment protocols.

The clinical trial focuses on individuals diagnosed with **Acute Myocardial Infarction**. The study population includes both male and female participants over the age of 18, who have undergone a percutaneous coronary intervention (PCI) procedure within 48 hours to 14 days prior to inclusion. Participants are required to provide written consent after being fully informed about the study. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. The selection criteria emphasize the availability of BIO-RISK-EVENT score parameters. Participants' lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as a **randomized**, **controlled** study to evaluate the efficacy of intensified residual risk management compared to standard guideline treatment in patients with a high risk for recurrent cardiovascular events, specifically following an **acute myocardial infarction**. The trial will involve the administration of investigational medicinal products, including **icosapent ethyl**, **colchicine**, and **empagliflozin**, all administered orally. The trial is expected to commence recruitment on July 1, 2025, and conclude by June 30, 2028, with a maximum treatment period of 234 days for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age over 18, recent percutaneous coronary intervention (PCI) for acute myocardial infarction, and availability of BIO-RISK-EVENT score parameters. Following the screening, participants will be randomized into either the intensified treatment group or the standard treatment group. Regular follow-up visits will be scheduled to monitor the participants' health status, adherence to the treatment regimen, and to collect data on cardiovascular outcomes. The primary endpoint is the time to the first event of a composite of cardiovascular outcomes, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for urgent coronary revascularization, and hospitalization for heart failure. Secondary endpoints include time to first events for individual cardiovascular outcomes and all-cause mortality.

The expected length of participant involvement is up to 234 days, with conditions for early termination including withdrawal of consent, adverse events, or any medical condition that contraindicates continued participation. The trial will adhere to rigorous ethical standards, ensuring that all participants provide informed consent prior to enrollment. The study's design and procedures aim to provide robust data on the efficacy of the investigational treatments in reducing the risk of recurrent cardiovascular events in the target population.

The clinical trial involves the administration of **Vazkepa 998 mg soft capsules**, which contain the active substance **icosapent ethyl**. This medication is provided in the form of soft capsules and is administered orally. The maximum daily dose is 4 grams, with a total maximum dose of 6539 grams over a treatment period of 234 days. The pharmaceutical form is specifically designed for oral administration, ensuring optimal absorption and efficacy. The trial aims to evaluate the efficacy of this treatment in managing cardiovascular risk factors in patients at high risk for recurrent cardiovascular events.

In addition to the experimental treatment, the study includes the use of **colchicine**, which is administered in a pharmaceutical form denoted as PHF00082MIG. This medication is also taken orally, with a maximum daily dose of 0.5 milligrams and a total maximum dose of 810 milligrams over the same treatment period of 234 days. Colchicine is utilized as a comparator treatment to assess its effectiveness in conjunction with the primary experimental medication.

Another non-experimental treatment used in the study is **empagliflozin**, also provided in the PHF00082MIG form. This medication is administered orally, with a maximum daily dose of 10 milligrams and a total maximum dose of 16200 milligrams over 234 days. Empagliflozin serves as an additional comparator treatment, allowing for a comprehensive evaluation of its role in cardiovascular risk management.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed treatment regimen. The study is designed to rigorously assess the efficacy of these treatments in achieving the primary objective of intensified residual risk management compared to standard guideline treatment.

The efficacy of the clinical trial will be assessed by evaluating the time to the first event of a composite of cardiovascular outcomes. These outcomes include cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for urgent coronary revascularization, and hospitalization for heart failure. The primary endpoint focuses on the time to the first occurrence of these composite cardiovascular events.

Secondary endpoints will further assess efficacy by measuring the time to first events for individual outcomes such as cardiovascular death, all-cause mortality, non-fatal myocardial infarction, non-fatal stroke, and hospitalizations for urgent coronary revascularization and heart failure. Additional secondary endpoints include the time to first events for any urgent revascularization procedures involving coronary, carotid, or peripheral arteries, as well as major adverse limb events.

The trial aims to compare the efficacy of intensified residual risk management against standard guideline treatment in patients with high risk for recurrent cardiovascular events. The assessment will be conducted over a maximum treatment period of 234 days, with the primary and secondary endpoints being measured at specified time points throughout the trial duration. The trial will utilize a randomized controlled design to ensure the reliability and validity of the efficacy outcomes.