Evaluation of Antiplatelet Therapy Discontinuation Versus Continuation in Young Patients Post-Cryptogenic Stroke: A Comparative Analysis of Carbasalate Calcium, Clopidogrel, and Dipyridamole

The primary objective of the study is to evaluate whether the **discontinuation** of antiplatelet therapy is non-inferior to its continuation in preventing major cardiovascular events three to ten years after a cryptogenic transient ischemic attack (TIA) or ischemic **stroke** at a young age. This is clinically relevant as it may influence long-term management strategies for young patients who have experienced a cryptogenic stroke or TIA, potentially reducing unnecessary medication use and associated risks.

Secondary objectives include:

• Investigating whether discontinuation of antiplatelet therapy reduces the risk of major bleeding.
• Assessing whether discontinuation reduces all-cause mortality.
• Evaluating the impact of discontinuation on quality of life.
• Determining the cost-effectiveness of discontinuation.

The clinical trial focuses on individuals who have experienced a **stroke** or transient ischemic attack (TIA) with evidence of ischemia on imaging, occurring three to ten years prior to study participation. The study population includes both male and female subjects, aged 18 to 49 years at the time of their TIA or ischemic stroke. Participants are selected based on a cryptogenic etiology, meaning no other cause was identified after a comprehensive standard work-up, which includes brain and cervical artery imaging, routine blood tests, cardiac rhythm monitoring, and echocardiography. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the non-inferiority of discontinuing **antiplatelet therapy** compared to its continuation in preventing major cardiovascular events in patients who have experienced a cryptogenic **stroke** or transient ischemic attack (TIA) at a young age. This study is a randomized, double-blind, controlled trial, categorized as a low-intervention clinical trial. The trial will span from the estimated recruitment start date in September 2024 to the estimated end date in September 2031, with a maximum treatment period of 260 days for participants.

Participants will be randomly assigned to either continue or discontinue antiplatelet therapy, which includes medications such as **clopidogrel** and **acetylsalicylic acid**. The trial will involve several study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, history of ischemic stroke or TIA, and cryptogenic etiology. Follow-up visits will be scheduled to monitor the participants' health status, adherence to the treatment protocol, and any adverse events. The end-of-study visit will assess the primary endpoint, which is a composite of major vascular events, including TIA, stroke, myocardial infarction, or death from vascular causes. Secondary endpoints include major bleeding, all-cause mortality, cost-effectiveness, and quality of life.

The expected length of participant involvement is up to 260 days, with conditions for early termination including significant adverse events or withdrawal of consent. The trial's methodology ensures that the additional monitoring procedures do not pose more than minimal additional risk or burden compared to normal clinical practice. The study aims to provide evidence-based insights into the safety and efficacy of antiplatelet therapy discontinuation in this specific patient population.

The clinical trial involves the administration of several **antiplatelet therapies** to evaluate their efficacy in preventing major cardiovascular events following a cryptogenic stroke in young patients. The experimental medication, **Carbasalate Calcium**, is administered orally in a pharmaceutical form denoted as PHF00059MIG. The maximum daily dose is 80 mg, with a total maximum dose of 146,000 mg over a treatment period of 60 days. This compound is chemically derived and serves as a comparator in the trial.

**Clopidogrel**, marketed as Plavix 75 mg film-coated tablets, is another treatment used in the study. It is administered orally with a maximum daily dose of 75 mg and a total maximum dose of 19,500 mg over a 260-day treatment period. This medication is also chemically derived and acts as a comparator in the trial. Another formulation of Clopidogrel, branded as Clopidogrel Viatris 75 mg film-coated tablets, is included in the study. It is administered orally, but specific dosing information is not provided, indicating a role as a test product in the trial.

The trial also includes a combination therapy of **Dipyridamole** and **Acetylsalicylic Acid** (ASA), administered orally in a pharmaceutical form identified as PHF00131MIG. The maximum daily dose for this combination is 400 mg, with a total maximum dose of 730,000 mg over a 60-day treatment period. This combination therapy is chemically derived and serves as a comparator in the study.

All treatments are administered orally, and participant compliance is monitored throughout the trial. The study aims to determine whether discontinuation of antiplatelet therapy is non-inferior to its continuation in preventing major cardiovascular events in the specified patient population.

The efficacy of the clinical trial titled "Stopping or continuing platelet inhibitors after cryptogenic stroke at young age: STOP trial" will be assessed using a composite primary endpoint. This endpoint includes major vascular events, defined as transient ischemic attack (TIA) with imaging confirmation, stroke, myocardial infarction, or death from vascular causes. Secondary endpoints will include major bleeding, all-cause mortality, cost-effectiveness, and quality of life. These parameters will be measured and collected at specified intervals throughout the trial duration, which is estimated to conclude by September 2, 2031.

The trial aims to evaluate whether discontinuation of antiplatelet therapy is non-inferior to its continuation in preventing major cardiovascular events three to ten years after a cryptogenic TIA or ischemic stroke in young adults. The study will involve the use of antiplatelet therapies such as **carbasalate calcium**, **clopidogrel**, and **dipyridamole**. The trial is categorized as a low-intervention study, with additional monitoring procedures that do not pose more than minimal additional risk or burden compared to normal clinical practice. The trial is set to begin recruitment on September 1, 2024.