Recombinant Human Prourokinase for Acute Ischemic Stroke in the Extended Window Selected by CT-Based Artificial Intelligence

This multicenter, prospective, randomized, double-blind, placebo-controlled trial aims to evaluate the efficacy and safety of intravenous recombinant human prourokinase (rhPro-UK) in patients with acute ischemic stroke treated more than 4.5 hours and up to 24 hours after stroke onset, selected using a noncontrast computed tomography-based artificial intelligence (CT-AI) tissue-window algorithm. A total of 826 participants will be randomly assigned in a 1:1 ratio to receive intravenous rhPro-UK or matching placebo, in addition to guideline-recommended standard stroke care. The primary outcome is the proportion of participants achieving a modified Rankin Scale (mRS) score of 0-1 at 90 ± 7 days. Secondary outcomes include functional outcomes, changes in neurological deficits, early neurological improvement at 24 hours and 7 days, and tissue reperfusion at 24-48 hours. Safety outcomes include symptomatic intracranial hemorrhage, parenchymal hematoma, all-cause mortality, and serious systemic bleeding.

Inclusion Criteria 1. Age ≥18 years. 2. Clinically diagnosed acute ischemic stroke. 3. Time from stroke onset to randomization \>4.5 hours and ≤24 hours. For patients with unknown onset time or wake-up stroke, the estimated onset time will be defined as the midpoint between the last known well time and symptom discovery time. 4. Baseline National Institutes of Health Stroke Scale (NIHSS) score of 4-25. 5. Pre-stroke modified Rankin Scale (mRS) score of 0-1. 6. No planned endovascular treatment at randomization. Patients with large vessel occlusion who are eligible for endovascular treatment must undergo independent evaluation and discussion before study enrollment. Patients who are planned to receive endovascular treatment will not be enrolled. 7. Meeting the CT-AI tissue-window selection criteria: * Predicted ischemic core volume ≤70 mL; * Hypoperfusion-to-core volume ratio \>1.2; * Difference between hypoperfusion and ischemic core volumes ≥10 mL. 8. Written informed consent provided by the participant or their legally authorized representative. Exclusion Criteria 1. Baseline CT showing intracranial hemorrhage, subarachnoid hemorrhage, brain tumor, brain abscess, or other non-ischemic lesions. 2. Baseline CT showing an extensive infarction, severe cerebral edema, or mass effect, or the investigator determines that the risks of intravenous thrombolysis substantially outweigh the potential benefits. 3. Contraindications specified in the prescribing information for recombinant human prourokinase for injection or current intravenous thrombolysis guidelines, other than the extended treatment time window specifically evaluated in this trial, including but not limited to: * Any history of intracranial hemorrhage; * Severe head trauma or stroke, including ischemic stroke, within the previous 3 months; * Recent major surgery or severe trauma; * Active internal bleeding; * Significant coagulation abnormalities; * Platelet count \