This randomized, double-blind, placebo-controlled phase III clinical trial aims to evaluate the efficacy and safety of intravenous recombinant human Prourokinase (rhPro-UK) in acute ischemic stroke patients with large vessel occlusion presenting 4.5-24 hours after last known well. The study will address two primary questions: 1) Whether rhPro-UK enhances pre-thrombectomy reperfusion rates and improves 90-day functional outcomes compared to placebo; 2) Whether rhPro-UK increases the risk of symptomatic intracranial hemorrhage and mortality.
Participants will be randomized to receive an intravenous bolus of rhPro-UK or matching placebo, with a total dose of 35mg (15mg administered as an intravenous push within 5 minutes, and the remaining 20mg continuously infused intravenously over 30 minutes). Key assessments include repeat neuroimaging (CT/CTA or MRI/MRA) at 24 hours post-treatment to evaluate reperfusion, NIH Stroke Scale score at day 5-7, and modified Rankin Scale score assessment at 90 days. Safety monitoring will focus on hemorrhagic transformation and mortality events throughout the study period.
Age ≥18 years;
Acute ischemic stroke presenting within 4.5-24 hours of last known well;
No significant pre-stroke functional disability: for age <80 years, pre-stroke modified Rankin scale (mRS) ≤2; for age ≥80 years, prestroke mRS ≤1;
Baseline NIHSS score ≥6;
Intracranial hemorrhage confirmed by CT/MRI;
Onset accompanied by epileptic seizures, resulting in questionable stroke diagnosis and inability to obtain an accurate baseline NIHSS score;
Women who are pregnant or breastfeeding, or have a positive serum β-HCG test upon admission;
Already received intravenous thrombolytic after index stroke;
Parallel
Intravenous rhPro-UK
DrugPatients will receive intravenous rhPro-UK
Intravenous placebo
DrugPatients will receive intravenous placebo
Endovascular thrombectomy
Procedure/SurgeryPatients will receive endovascular thrombectomy
Proportion of patients functionally independent (mRS score 0 to 2) at 90 days
The modified Rankin Scale (mRS) is employed to assess patients' activities of daily living and the degree of disability. It grades patients' functional ability on a scale from 0 to 6, with a score of 0 indicating no symptoms and 6 representing death. An mRS score of 0-2 indicates functional independence.
Distribution of mRS scores at 90 days
The Modified Rankin Scale (mRS) is employed to assess patients' activities of daily living and the degree of disability. It grades patients' functional ability on a scale from 0 to 6, with a score of 0 indicating no symptoms and 6 representing death. The mRS score reflects the neurological functional status of stroke patients.
Shift in mRS score at 90 days
The modified Rankin Scale (mRS) is employed to assess patients' activities of daily living and the degree of disability. It grades patients' functional ability on a scale from 0 to 6, with a score of 0 indicating no symptoms and 6 representing death. An mRS score shift reflects the improvement in the patient's neurological function.
Proportion of excellent functional outcome (mRS score 0 to 1) at 90 days
The modified Rankin Scale (mRS) is employed to assess patients' activities of daily living and the degree of disability. It grades patients' functional ability on a scale from 0 to 6, with a score of 0 indicating no symptoms and 6 representing death. An mRS score of 0-1 indicates excellent functional outcome.
Score on the EQ-5D-5L scale at 90 days
The EuroQoL 5-Dimension 5-Level (EQ-5D-5L) is a standardized health-related quality of life measurement instrument developed by the EuroQoL Group, primarily used to assess an individual's health status across multiple dimensions and their overall quality of life. The EQ-5D-5L describes an individual's health state based on five dimensions: Mobility, Self-care, Usual activities, Pain/Discomfort, and Anxiety/Depression. Scores range from 0, representing "the worst imaginable health," to 100, representing "the best imaginable health."
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First Affiliated Hospital Xi'an Jiaotong University
Lead sponsor
Tasly Pharmaceutical Group Co., Ltd
Collaborator
Peking Union Medical College Hospital
Collaborator
