Efficacy and Safety of Tirofiban Versus Intravenous Acetylsalicylic Acid in Endovascular Treatment of Acute Ischemic Stroke with Tandem Lesion

The primary objective of this randomized multi-center clinical trial is to assess the **efficacy** and **safety** of tirofiban versus aspirin in patients with **acute ischemic stroke** secondary to tandem injury. This will be evaluated by determining the rate of **reocclusion** and the rate of symptomatic bleeding, defined as any hemorrhagic transformation associated with a worsening of 4 or more points on the National Institutes of Health Stroke Scale. This is clinically relevant as it aims to identify a more effective and safer treatment option for patients undergoing recanalization therapy through endovascular treatment.

Secondary objectives include:

• Determining the rescue therapy rate in the presence of intra-stent aggregation phenomena during the procedure.
• Detection of good functional prognosis rates at 90 days in different subgroups, defined as a score on the modified Rankin scale (mRS) between 0-2.
• Improving the pathophysiological knowledge of complications associated with the endovascular treatment of tandem lesions (reocclusion) through the identification of related plasma biomarkers.
• Assessment of any identified biomarkers as a therapeutic target for reocclusion.
• Evaluating reocclusion or significant restenosis at 30 days.

The clinical trial focuses on evaluating the efficacy and safety of tirofiban versus aspirin in patients with **acute ischemic stroke** secondary to tandem injury. The study population includes both male and female participants aged 18 years and older. The trial does not involve a vulnerable population. Participants are required to have an acute ischemic stroke of the anterior territory secondary to a tandem lesion, with an indication for thrombectomy treatment and the need for cervical stent placement. The trial does not specify the total number of participants, as the sponsor has not provided this information. The selection criteria include specific intracranial occlusion locations and an ASPECTS score of 6 or higher. Participants must provide signed informed consent. The study does not highlight any specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the **efficacy** and safety of **tirofiban** compared to **aspirin** in patients with **acute ischemic stroke** secondary to tandem injury. This is a randomized, double-blind, controlled trial with a multi-center approach. The trial aims to determine the rate of reocclusion and symptomatic bleeding, defined as any hemorrhagic transformation associated with a worsening of 4 or more points on the National Institutes of Health Stroke Scale. The trial is expected to last until December 2024, with recruitment having started in May 2022.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, stroke characteristics, and informed consent. Follow-up visits will be scheduled to monitor the participants' response to treatment and any adverse events. The end-of-study visit will assess the primary and secondary endpoints, including carotid reocclusion, platelet aggregation phenomena, and symptomatic intracranial hemorrhage. The secondary endpoint focuses on the functional prognosis, defined as a score on the modified Rankin Scale between 0-2 at 90 days.

The expected length of participant involvement is up to 90 days, depending on the treatment arm. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or protocol violations. The trial will adhere to the current recommendations of the Clinical Practice Guidelines, ensuring that all procedures align with ethical standards and regulatory requirements.

The clinical trial involves the administration of **Tirofiban Hydrochloride Monohydrate**, marketed as AGRASTAT 50 microgrammes/ml, solution for perfusion. This experimental medication is provided in the form of a **solution for infusion** and is administered via **intravenous infusion**. The maximum daily dose is 500 micrograms, with a total maximum dose of 5283.4 micrograms, and the treatment period is limited to one day. The product is manufactured by CORREVIO and is authorized in France.

**D,L-Lysine Acetylsalicylate**, marketed as Inyesprin, is used as a comparator treatment in the study. It is available in the form of an **injection** and is administered through **intravenous infusion**. The maximum daily and total dose is 500 milligrams, with a treatment period of one day. This product is manufactured by ARISTO PHARMA IBERIA, S.L. and is authorized in Spain.

**Acetylsalicylic Acid**, commonly known as aspirin and marketed as A.A.S. 100 mg comprimidos, is another comparator treatment. It is provided in **tablet** form and administered **orally**. The maximum daily dose is 300 milligrams, with a total maximum dose of 9200 milligrams over a treatment period of 90 days. This product is manufactured by OPELLA HEALTHCARE SPAIN, S.L. and is authorized in Spain.

**Clopidogrel**, marketed as Clopidogrel TecniGen 75 mg comprimidos recubiertos con película EFG, is used as an auxiliary treatment. It is available as a **film-coated tablet** and administered **orally**. The maximum daily dose is 300 milligrams, with a total maximum dose of 2475 milligrams over a treatment period of 30 days. This product is manufactured by TECNIMEDE ESPAÑA IND. FCA., S.A. and is authorized in Spain.

The efficacy of the clinical trial will be assessed by evaluating both primary and secondary endpoints. The primary endpoints include the rate of carotid reocclusion, **platelet aggregation phenomena**, and symptomatic intracranial hemorrhage (sICH). These parameters will be measured to determine the effectiveness of tirofiban versus aspirin in patients with acute ischemic stroke secondary to tandem injury. The secondary endpoint focuses on the functional prognosis, defined as a score on the modified Rankin Scale (mRS) between 0-2 at 90 days, indicating a good functional outcome.

The trial will utilize validated scales and clinical assessments to measure these endpoints. The National Institutes of Health Stroke Scale (NIHSS) will be employed to assess symptomatic bleeding, specifically any hemorrhagic transformation associated with a worsening of 4 or more points on the NIHSS. The modified Rankin Scale will be used to evaluate the functional prognosis at the 90-day mark. These assessments will be conducted at specified timepoints throughout the trial to ensure comprehensive data collection and analysis.