Evaluation of Cangrelor Tetrasodium with Mechanical Thrombectomy in Perfusion Imaging-Selected Acute Ischemic Stroke Patients: A Multicenter Randomized Controlled Trial

The primary objective of this study is to evaluate the efficacy of the **P2Y12 inhibitor** cangrelor, in addition to mechanical thrombectomy (MT) and best medical management (BMM), compared to MT and BMM alone, on the functional outcome at 3 months in patients with acute ischemic stroke (AIS) selected based on perfusion imaging within 0 to 24 hours after stroke onset. This objective is clinically relevant as it aims to determine whether the addition of cangrelor can improve long-term functional recovery in AIS patients, potentially leading to enhanced treatment protocols and better patient outcomes.

Secondary objectives include: - Evaluating the efficacy of cangrelor in addition to MT and BMM compared to MT and BMM on functional outcome at 3 months ("shift analysis"). - Assessing the efficacy of cangrelor on reperfusion results at the end of treatment. - Determining the efficacy of cangrelor on early neurological improvement at 24 hours. - Evaluating the impact of cangrelor on stroke volume at 24-36 hours.

The clinical trial focuses on evaluating the efficacy of a **P2Y12 inhibitor** (cangrelor) in patients with **acute ischemic stroke**. The study population includes both male and female participants aged 18 years and older. Participants are selected based on specific criteria, including anterior circulation intracranial large artery occlusion confirmed by CTA or MRA, and symptoms onset within 24 hours at imaging. The trial involves a vulnerable population, and participants must have a pre-stroke mRS score of 2 or less and an NIHSS score of 6 or more. The sponsor has not provided information regarding the total number of participants. The trial does not specify any particular lifestyle considerations such as diet or physical activity. Key inclusion criteria involve specific brain imaging results, but these are not the primary focus of this description.

The clinical trial is designed to evaluate the efficacy of **cangrelor tetrasodium**, a P2Y12 inhibitor, in addition to mechanical thrombectomy (MT) and best medical management (BMM) compared to MT and BMM alone in patients with **acute ischemic stroke**. This study is a multicentric, randomized, controlled trial with an estimated duration from March 2022 to March 2026. The trial will involve a double-blind methodology to ensure unbiased results. Participants will be randomly assigned to either the treatment group receiving cangrelor or the control group receiving standard care without the investigational drug.

The trial will include several study visits, beginning with a screening visit to confirm eligibility based on criteria such as age (18 or older), anterior circulation large artery occlusion, and specific imaging findings. Following successful screening, participants will be enrolled and undergo baseline assessments. The primary endpoint is a favorable functional outcome defined by a modified Rankin Scale (mRS) score of 2 or less at 3 months. Secondary endpoints include mRS shift analysis, rates of reperfusion, changes in NIHSS, and mortality rates.

Participants will be involved in the study for a period of up to 3 months, with follow-up visits scheduled at 24-36 hours post-treatment and at 3 months to assess outcomes. The study may be terminated early for individual participants if they experience adverse events, fail to adhere to the protocol, or withdraw consent. The trial aims to provide valuable insights into the potential benefits of adding cangrelor to the treatment regimen for acute ischemic stroke, with the ultimate goal of improving patient outcomes.

The clinical trial involves the administration of **Kengrexal**, a pharmaceutical product containing the active substance **cangrelor tetrasodium**. Kengrexal is formulated as a **powder for concentrate for solution for injection/infusion**. The product is intended for intravenous infusion, with a maximum daily dose of 150 mg. The treatment period is limited to a maximum of one day. The product is manufactured by Chiesi Limited and is used off-label in this study. The chemical origin of the active substance ensures its purity and consistency for clinical use.

In addition to the experimental treatment with Kengrexal, participants in the study may receive standard-of-care therapy, which includes mechanical thrombectomy (MT) and best medical management (BMM). These non-experimental treatments are provided to all participants as part of the study protocol to ensure comprehensive care for patients with acute ischemic stroke (AIS). The combination of these therapies aims to evaluate the efficacy of the P2Y12 inhibitor, cangrelor, in improving functional outcomes at three months post-stroke onset.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the achievement of a favorable functional outcome, defined by a **modified Rankin Scale (mRS)** score of 2 or less at 3 months post-treatment. This scale is a widely used and validated tool for measuring the degree of disability or dependence in daily activities of people who have suffered a stroke.

Secondary endpoints include several measures: a shift analysis of the mRS at 3 months, the rate of near or complete reperfusion at the end of treatment as defined by a modified treatment in cerebral infarction (mTICI) score of 2c or 3, and the rate of successful reperfusion with mTICI scores of 2b, 2c, or 3. Additionally, changes in the National Institutes of Health Stroke Scale (NIHSS) from baseline to 24 hours after treatment will be evaluated. The volume of the infarct will be assessed using the ASPECTS score at 24-36 hours. Other secondary endpoints include the rate of all-cause mortality at 3 months, the rate of symptomatic intracranial hemorrhage according to the Heidelberg definition with at least a 4-point worsening in NIHSS at 24-36 hours post-treatment, and the rate of any intracranial hemorrhage according to the Heidelberg definition at 24-36 hours post-treatment.