Evaluation of Hemodynamic Optimization Protocols Using Urapidil, Phenylephrine Hydrochloride, and Labetalol Hydrochloride in Acute Ischemic Stroke Post-Endovascular Therapy

The primary objective of the HOPE study is to evaluate the **clinical benefit** of standard blood pressure management compared to a specific protocol aimed at **hemodynamic optimization** following mechanical thrombectomy in patients with **acute ischemic stroke**. This protocol involves adjusting blood pressure targets based on the degree of recanalization achieved during the procedure. The clinical relevance of this study lies in its potential to improve patient outcomes by optimizing cerebral perfusion, thereby reducing the risk of further neurological damage and enhancing recovery post-stroke.

The clinical trial involves participants diagnosed with **Acute Ischemic Stroke**. The study population includes both male and female subjects, with an age range encompassing adults and the elderly. The trial does not involve a vulnerable population. Participants were selected based on specific criteria, including having experienced a large intracranial vessel occlusion within 24 hours of symptom onset and having undergone mechanical thrombectomy. Successful recanalization, defined by a TICI score of 2b, 2c, or 3, is required. Additionally, participants must have had a prior score on the modified Rankin Scale (mRS) of 0, 1, or 2. The total number of participants is not provided by the sponsor. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the **hemodynamic optimization** of cerebral perfusion following endovascular therapy in patients with **acute ischemic stroke**. This is a randomized, double-blind, controlled trial aimed at comparing the clinical benefits of standard blood pressure management post-mechanical thrombectomy against a specific protocol that targets blood pressure based on the degree of recanalization achieved. The trial is categorized as a Phase IV study, indicating it involves drugs that are already approved and used in accordance with their marketing authorization. The trial is expected to run from April 2021 to September 2025, with a total duration of approximately four years and five months.

Participants will be involved in the study for a maximum treatment period of three days. The study includes several key visits: an initial screening visit to confirm eligibility, follow-up visits to monitor progress, and an end-of-study visit to assess outcomes. The inclusion criteria require participants to have experienced an acute ischemic stroke with large intracranial vessel occlusion within 24 hours of symptom onset and to have undergone successful mechanical thrombectomy, defined by a TICI score of 2b, 2c, or 3. Participants must also have a prior modified Rankin Scale (mRS) score of 0, 1, or 2, and provide informed consent.

The primary endpoint of the trial is a direct comparison between the two arms regarding the mRS score at 90 days post-randomization, analyzed on an intention-to-treat basis. The main effect parameter will be the odds ratio of change in the direction of a better result in the mRS, with a 95% confidence interval. Participants may be terminated early from the study if they do not meet the inclusion criteria, experience adverse effects, or withdraw consent. The investigational drugs used in the trial include **urapidil**, **phenylephrine hydrochloride**, and **labetalol hydrochloride**, all administered intravenously. These drugs are used as per their approved indications, ensuring minimal additional risk or burden compared to usual practice.

The clinical trial involves the administration of **Urapidil Accord 5 mg/ml**, a **solution for injection/infusion**. The active substance is **urapidil**, classified under the ATC code C02CA06 as an alpha-adrenergic receptor antagonist. The pharmaceutical form is a solution intended for intravenous administration. The maximum daily dose is 5 mg/ml, with a total dose not exceeding 5 mg/ml over a treatment period of up to 3 days. The product is manufactured by Accord Healthcare S.L.U. and is not a pediatric formulation. Participant compliance will be monitored through standard clinical trial procedures.

Another treatment used in the trial is **Fenilefrina Altan 0.1 mg/ml**, also a **solution for injection/infusion**. The active substance is **phenylephrine hydrochloride**, categorized under the ATC code C01CA06 as a cardiac stimulant. This medication is administered intravenously, with a maximum daily dose of 100 µg/kg and a total dose not exceeding 100 µg/kg over a 3-day treatment period. The product is provided by Altan Pharmaceuticals S.A. and is not formulated for pediatric use. Compliance monitoring will be conducted as per the trial protocol.

The trial also includes the administration of **Trandate 5 mg/ml Solution for Injection**, containing the active substance **labetalol hydrochloride**. This medication is classified under the ATC code C07AG01 as an alpha and beta blocking agent. It is available as a solution for injection and is administered intravenously. The maximum daily dose is 0.8 mg/l, with a total dose not exceeding 0.8 mg/l over a treatment period of up to 3 days. The product is manufactured by RPH Pharmaceuticals AB and is not intended for pediatric use. Participant adherence to the dosing schedule will be monitored throughout the trial.

The efficacy of the clinical trial titled "A randomized trial on Hemodynamic Optimization of cerebral Perfusion after Endovascular therapy in patients with acute ischemic stroke (HOPE study)" will be assessed primarily through a direct comparison of the **modified Rankin Scale (mRS)** scores at 90 days post-randomization between the two arms of the trial. This will involve an intention-to-treat analysis, focusing on the odds ratio (OR) of change in the direction of a better result in the mRS, along with its 95% confidence interval. The mRS is a widely recognized scale used to measure the degree of disability or dependence in daily activities of people who have suffered a stroke.