Tailored antiplatelet secondary prevention in non-cardioembolic ischemic stroke: a phase IV gender-stratified randomized controlled trial (TAILOR trial)

The primary objective is to demonstrate that a tailored prescription of antiplatelet drugs can reduce the rate of 12-month major cardiovascular events compared to usual care in patients with non-cardioembolic ischemic stroke. This approach aims to optimize secondary prevention strategies by individualizing antiplatelet therapy selection, potentially improving clinical outcomes in this patient population.

The secondary objectives include:

• Assessment of adverse events, including major and minor bleeding complications associated with antiplatelet therapy

• Evaluation of treatment adherence to the prescribed antiplatelet regimen

• Exploration of gender-based differences in treatment response and outcomes

• Evaluation of the rate of CYP2C19*2 and CYP2C19*17 polymorphisms, which may influence antiplatelet drug metabolism and efficacy

• Comparison of the rate of 3-month major cardiovascular events between the tailored approach and usual care

The sponsor did not provide information regarding the total number of participants enrolled in this clinical trial. The study population included both **male** and **female** adults aged 18 years and older who experienced **non-cardioembolic ischemic stroke** within 14 days prior to enrollment. Participants were selected based on their eligibility to initiate or continue **secondary prevention** treatment with single or double **anti-platelet therapy** following the index stroke event. The trial population comprised individuals classified within adult and elderly age categories. Written **informed consent** was required from all participants, with provisions allowing consent to be obtained from incapacitated patients in accordance with applicable national legislation. The study included a vulnerable population as defined by regulatory standards.

This study is a phase IV, gender-stratified, randomized controlled trial designed to evaluate tailored antiplatelet secondary prevention in patients with non-cardioembolic ischemic stroke. The trial is classified as a low-intervention clinical trial, as the investigational medicinal products are used within the indication and dosages recommended by international guidelines and according to good clinical practice. The primary objective is to demonstrate that a tailored prescription of antiplatelet drugs can reduce the rate of 12-month major cardiovascular events compared to usual care. The study will compare three antiplatelet agents administered via the oral route: ticlopidine hydrochloride (maximum daily dose 250 mg, maximum total dose 500 mg), clopidogrel (maximum daily dose 75 mg, maximum total dose 75 mg), and acetylsalicylic acid (maximum daily dose 100 mg, maximum total dose 100 mg). Each treatment period is planned for a maximum of 3 months. The estimated recruitment start date is February 16, 2026, with an estimated end date of August 31, 2029.

The primary endpoint is the 12-month cumulative incidence (time to first event) of the composite of ischemic stroke, myocardial infarction, or cardiovascular death. Secondary endpoints include adherence to treatment assessed at 3-month and 12-month follow-up visits using the 5-item Medication Adherence Report Scale (MARS-5) and responder status at follow-up aggregation testing, good functional status at 12 months defined according to modified Rankin Scale 0-2, 12-month incidence of single-items of the composite primary outcome, 12-month incidence of major and minor bleeding (composite safety outcome), gender differences in primary and secondary outcomes, prevalence of CYP2C19*2 and CYP2C19*17 polymorphisms between responders and non-responders, and 3-month cumulative incidence of the composite of ischemic stroke, myocardial infarction, or cardiovascular death.

Principal inclusion criteria are: aged 18 years or older, males and females, non-cardioembolic ischemic stroke within the previous 14 days, starting or continuing secondary prevention with single or double antiplatelet therapy after the index stroke, and written informed consent (informed consent can be obtained from incapacitated patients in accordance with national legislation). Participants will undergo a screening visit to assess eligibility, followed by scheduled follow-up visits at 3 months and 12 months to evaluate treatment adherence, functional status, and clinical outcomes. The expected length of participant involvement is 12 months from enrollment. Conditions that may lead to early termination from the study include withdrawal of consent, occurrence of serious adverse events requiring discontinuation of treatment, loss to follow-up, or investigator decision based on safety concerns or protocol violations.

The trial investigates three antiplatelet agents administered orally as part of a tailored secondary prevention strategy for non-cardioembolic ischemic stroke. All experimental medications are administered for a maximum treatment period of 3 months.

**Ticlopidine hydrochloride** is administered as TICLOPIDINA MYLAN GENERICS in the form of **coated tablets** containing 250 mg of the active substance. The medication is administered via the **oral route**. The maximum daily dose is 250 mg, with a maximum total dose of 500 mg, indicating a twice-daily dosing regimen.

**Clopidogrel** is administered as Clopidogrel Zentiva in the form of **film-coated tablets** containing 75 mg of the active substance. The medication is administered via the **oral route**. Both the maximum daily dose and maximum total dose are 75 mg, indicating once-daily administration.

**Acetylsalicylic acid** is administered as Acido Acetilsalicilico Aurobindo in the form of **gastro-resistant tablets** containing 100 mg of the active substance. The medication is administered via the **oral route**. Both the maximum daily dose and maximum total dose are 100 mg, indicating once-daily administration. The gastro-resistant formulation is designed to prevent dissolution in the stomach and ensure release in the intestinal tract.

Efficacy will be assessed through a primary endpoint measuring the 12-month cumulative incidence of the composite outcome consisting of **ischemic stroke**, **myocardial infarction**, or **cardiovascular death**, evaluated as time to first event. Secondary efficacy endpoints include adherence to treatment assessed at 3-month and 12-month follow-up visits using the 5-item Medication Adherence Report Scale (MARS-5), with good adherence defined as a score of 20 or greater on the total scale ranging from 5 to 25. Responder status will be determined through aggregation testing based on ASPI/ADP measurements appropriate to the administered antiplatelet drug. Good functional status at 12 months will be evaluated and adjudicated using the **modified Rankin Scale** with scores of 0 to 2 indicating favorable outcome. Additional secondary endpoints comprise the 12-month incidence of individual components of the composite primary outcome, the 3-month cumulative incidence of the composite outcome consisting of ischemic stroke, myocardial infarction, or cardiovascular death, and gender differences in both primary and secondary outcomes. The prevalence of **CYP2C19*2** and **CYP2C19*17** polymorphisms will be analyzed comparing responders and non-responders. Safety will be monitored through the 12-month incidence of major and minor bleeding as a composite safety outcome, with the incidence of individual components of this composite safety outcome also evaluated as a secondary endpoint.