Intravenous rhPro-UK Before Stroke Thrombectomy in the Extended Time Window (BRIDGE-PUK EXTEND)

Prior treatment

• Already received intravenous thrombolytic after index stroke;
• History of prior intracranial hemorrhage, including cerebral parenchymal hemorrhage, subarachnoid hemorrhage, and subdural/extradural hematoma;
• Concurrent participation in other investigation clinical trials;

Other illness

• 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;
• Active bleeding or bleeding tendency, such as gastrointestinal bleeding, urinary tract bleeding, retinal hemorrhage, etc., or presence of coagulation dysfunction;
• History of major recent surgery or trauma, such as intracranial or spinal surgery within the past 3 months, major surgery within the past 2 weeks, or severe head trauma within the past 3 weeks;
• Pre-existing neurological/psychiatric disorders interfering with neurological assessment;
• Terminal illness with life expectancy \<6 months;
• Presence of other conditions deemed by the investigator as unsuitable for participation in the study.

Lab values

• Women who are pregnant or breastfeeding, or have a positive serum β-HCG test upon admission;
• Baseline blood glucose \<2.8 mmol/L or \>22.2 mmol/L;
• Received low molecular weight heparin within 24 hours, or oral anticoagulants with an International Normalized Ratio (INR) \>1.7, or thrombin inhibitors within 48 hours, among others;

Other

• Arterial tortuosity or other vascular anomalies precluding endovascular access to target vessel;
• Space-occupying intracranial tumors (except for small meningiomas);
• Intracranial aneurysm or arteriovenous malformation;

• 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;
• Imaging criteria of BOTH:
  • 1\. Occlusion on CTA/MRA in one of the following vessels: M1/M2 segment of middle cerebral artery, A1 segment of anterior cerebral artery, V4 segment of vertebral artery, basilar artery, or P1 segment of posterior cerebral artery. For A1, or P1 occlusions, vessel diameter must be ≥0.75 mm; 2. For anterior circulation occlusion: CTP/MRP demonstrating mismatch ratio ≥1.8, absolute mismatch volume ≥15 mL, and ischemic core volume \<70 mL; OR have a mismatch between the presence of an abnormal signal on MRI diffusion-weighted imaging and no visible signal change on FLAIR. For posterior circulation occlusion: pc-ASPECTS score ≥6.
  • 6\. Plan to received endovascular thrombectomy; 7. The patient or their legal representative provides written informed consent.