Evaluation of De-escalation from Prasugrel and Ticagrelor to Clopidogrel in Acute Coronary Syndrome Using VerifyNow® Platelet Aggregation Measurement

The primary objective of the study is to evaluate whether **de-escalation** from potent antiplatelet agents, such as prasugrel and ticagrelor, to clopidogrel, guided by the VerifyNow® platelet aggregation measurement device, provides a beneficial effect in the management of **Acute Coronary Syndrome (ACS)**. This is clinically relevant as optimizing antiplatelet therapy can potentially reduce adverse cardiovascular events and improve patient outcomes in those with ACS.

Secondary objectives include assessing the occurrence of ischemic events over a one-year period, which encompasses: cardiovascular death, death from any cause, non-fatal acute myocardial infarction (AMI), acute cerebrovascular events (ACV), definitive stent thrombosis, and the need for unscheduled revascularization. These outcomes are critical for understanding the broader impact of antiplatelet therapy adjustments on patient health and long-term cardiovascular risk management.

The clinical trial involves participants diagnosed with **cardiovascular diseases**, specifically those experiencing Acute Coronary Syndrome (ACS). The study population includes both male and female subjects aged 18 years and above. Participants are required to have undergone Percutaneous Coronary Intervention (PCI) during their admission and must have been discharged on double antiplatelet therapy with Acetylsalicylic Acid and either Ticagrelor or Prasugrel. The trial does not include vulnerable populations. The sponsor has not provided information regarding the total number of participants. Selection criteria emphasize the ability of participants to understand the study's nature and provide written informed consent. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of de-escalating from more potent **antiplatelet agents** such as **prasugrel** and **ticagrelor** to **clopidogrel** in patients with **acute coronary syndrome** (ACS). This is a randomized, double-blind, controlled trial with a duration of 12 months. The trial aims to assess whether this de-escalation, guided by the VerifyNow® platelet aggregation measurement device, has a beneficial effect on treatment outcomes. The primary endpoint is the incidence of Net Adverse Cardiac Events (NACE), which includes death from vascular causes, non-fatal myocardial infarction (MI), non-fatal stroke, and bleeding classified as BARC type ≥ 2. Secondary endpoints include the incidence of cardiovascular death, non-fatal MI, stroke, thrombosis in the target lesion, and revascularization on the target lesion, all evaluated at 12 months.

Participants will be involved in the study for a maximum of 12 months. The study begins with a screening visit to confirm eligibility, which includes patients aged 18 years or older who have undergone percutaneous coronary intervention (PCI) with an absorbable polymer stent and are discharged on double antiplatelet therapy with acetylsalicylic acid and either ticagrelor or prasugrel. Following the screening, participants will be randomized to receive either the test or comparator treatment. Regular 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 the 12-month mark, where final assessments will be conducted to evaluate the primary and secondary endpoints.

Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or withdraw consent. The trial is categorized as a Phase IV clinical trial and is considered low-intervention. The estimated recruitment start date was July 2, 2021, with an anticipated end date of December 2, 2025. The trial involves the use of film-coated tablets administered orally, with the maximum daily doses being 180 mg for ticagrelor, 10 mg for prasugrel, and 75 mg for clopidogrel. The trial is conducted under the authorization of relevant regulatory bodies, ensuring compliance with ethical standards and scientific rigor.

The clinical trial involves the administration of **Brilique** 90 mg film-coated tablets, which contain the active substance **ticagrelor**. This medication is provided in the form of film-coated tablets and is administered orally. The maximum daily dose is 180 mg, divided into two doses of 90 mg each, taken twice daily. The treatment period for this medication is up to 12 months. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

Another treatment used in the trial is **Efient** 10 mg film-coated tablets, containing the active substance **prasugrel**. This medication is also administered orally in the form of film-coated tablets. The maximum daily dose is 10 mg, taken once daily. The treatment duration for Efient is also up to 12 months. Compliance with the dosing schedule will be closely monitored to ensure participants adhere to the prescribed treatment plan.

The trial also includes the use of **Plavix** 75 mg film-coated tablets, which contain the active substance **clopidogrel**. This medication is administered orally in the form of film-coated tablets. The maximum daily dose is 75 mg, taken once daily. The treatment period for Plavix is up to 12 months. Participant adherence to the dosing schedule will be monitored to ensure compliance with the treatment protocol.

In this clinical trial, the de-escalation from the more potent antiplatelet agents, prasugrel and ticagrelor, to clopidogrel is guided by the VerifyNow® platelet aggregation measurement device. This approach aims to evaluate the potential beneficial effects in the treatment of Acute Coronary Syndrome (ACS). The trial does not involve the use of a placebo or any other non-experimental treatments. All medications are chemically derived and have been authorized for use in the European Union.

Efficacy in the clinical trial titled "VerifyNow to Optimise Platelet Inhibition in Coronary Acute Syndrome (VERONICA)" will be assessed using specific primary and secondary endpoints. The primary endpoint is the incidence of **Net Adverse Cardiac Events (NACE)**, which is a composite measure including death from vascular causes, non-fatal myocardial infarction (MI), non-fatal stroke, and bleeding classified as BARC type ≥ 2, evaluated at 12 months. Secondary endpoints include the incidence of cardiovascular death, overall death, non-fatal MI, stroke, thrombosis in the target lesion, revascularization on the target lesion, and bleeding (BARC criteria ≥ 2), all assessed at 12 months.

The trial aims to determine the efficacy of de-escalating from more potent antiplatelet agents, **prasugrel** and **ticagrelor**, to **clopidogrel**, guided by the VerifyNow® platelet aggregation measurement device, in the treatment of Acute Coronary Syndrome (ACS). The efficacy parameters will be collected and analyzed at the 12-month mark to evaluate the outcomes of the treatment strategy. The use of the VerifyNow® device is integral to the trial, as it guides the de-escalation process based on platelet aggregation measurements.