Ischemic cerebrovascular disease is a common neurological disorder with high incidence, mortality, and disability. Early reperfusion to salvage the ischemic penumbra is the cornerstone of acute ischemic stroke (AIS) treatment. Current reperfusion strategies include intravenous thrombolysis (IVT) and endovascular therapy (EVT). Although alteplase is the first-line thrombolytic agent, its recanalization rate for large vessel occlusion (LVO) is only 10-20%, and for medium vessel occlusion (MeVO), approximately 50% of patients fail to achieve recanalization, leading to poor outcomes. Prourokinase has recently been shown to be non-inferior to alteplase with a better safety profile, and studies suggest that repeated thrombolysis may improve recanalization rates in patients without early clinical improvement after standard IVT. Therefore, this study aims to evaluate the efficacy and safety of an additional intravenous infusion of prourokinase in AIS patients with confirmed medium or large vessel occlusion who show no significant clinical improvement at 1 hour after standard IVT (within 4.5 hours of symptom onset). Patients without early neurological improvement (e.g., \<2-point reduction in NIHSS) and persistent vessel occlusion on imaging will receive a second dose of prourokinase. The primary outcomes include 24-hour recanalization rate (by CTA/MRA), 90-day functional outcome (modified Rankin Scale), and safety endpoints (symptomatic intracranial hemorrhage, mortality). The hypothesis is that additional prourokinase following standard IVT in non-improving patients with medium or large vessel occlusion will significantly increase recanalization rates and improve clinical outcomes without an unacceptable increase in symptomatic intracranial hemorrhage.
Age ≥ 18 year;
Acute ischemic stroke presumably caused by large or medium vessel occlusion within 4.5 hours of onset, having received intravenous thrombolysis of prourokinase, and with no planned thrombectomy;
Measurable neurological deficit before the first intravenous thrombolysis, with NIHSS ≥ 4;
Baseline pc-ASPECTS/ASPECTS ≥ 6, and for posterior circulation infarction, a Pontine-Midbrain Index ≤ 2 (assessed by CT or DWI);
Planed for endovascular treatment;
Significant white matter hyperintensities (Fazekas score 3);
Any coagulation abnormality before the first thrombolysis, including INR > 1.5;
Receipt of dual antiplatelet therapy within 24 hours prior to thrombolysis.；
Parallel
prourokinase
DrugIntravenous administration of prourokinase (20 mg infused over a 30-minute period)
rate of vessel recanalization
proportion of excellent functional outcome (modified Rankin Scale (mRS) 0-1)
The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome
proportion of favorable functional outcome (modified Rankin Scale (mRS) 0-2)
The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome
ordinal distribution of modified Rankin Scale (mRS)
The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome
occurrence of early neurological improvement (ENI)
NI is defined as more than 4-point decrease in National Institute of Health stroke scale score; the minimum and maximum values of NIHSS are 0 and 42, respectively; higher NIHSS mean a worse outcome
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