Intra-arterial Recombinant Human TNK Tissue-type Plasminogen Activator (rhTNK-tPA) Thrombolysis for Acute Large Vascular Occlusion After Successful Mechanical Thrombectomy Recanalization

The goal of this clinical trial is to evaluate whether intra-arterial (IA) rhTNK-tPA thrombolysis can improve neurological outcomes in acute large vessel occlusion patients after successful mechanical thrombectomy (MT) recanalization between 4.5- 24 hours from symptom onset. Participants enrolled will be randomly assigned to study or control arm with a 1:1ratio. Study group will receive IA rhTNK-tPA thrombolysis (0.125 mg/kg, Max 12.5mg) plus best medical management, and control receive best medical management alone.

Inclusion Criteria:Clinical Inclusion Criteria:Age >18 years;NIHSS ≥2;Onset of symptoms to baseline CT imaging time: 4.5 to 24 hours, including wake-up stroke and unwitnessed stroke; Time of onset of symptoms is defined as "last known well" (LKW);Pre-stroke mRS score 0-1;Signed informed consent from patient or their health care proxy.Neuroimaging Inclusion Criteria:CTA/MRA proven intracranial artery occlusion: Intracranial Internal Carotid Artery (ICA)、M1 of Middle cerebral artery (MCA)、dominant M2 of MCA;ASPECTS ≥6 on non-contrast CT (NCCT) scan or DWI MRI;CT perfusion or MR perfusion: ischemic infarct core <70ml, mismatch ratio≥1.2, mismatch volume ≥15ml;Treated with MT resulting in an eTICI score 2b50-3 at end of the procedure. Patients with an eTICI score 2b50-3 on the diagnostic cerebral angiography before the onset of MT are also eligible for the study.Exclusion Criteria:Clinical Exclusion Criteria:IV thrombolysis used on admission;Contraindications to intravenous thrombolysis;Balloon angioplasty, permanent stenting and other situations during the endovascular procedure that require antiplatelet therapy or anticoagulant within the first 24h;IV heparin (heparinized saline allowed);Females who are pregnant, or those of child-bearing potential with positive urine or serum beta Human Chorionic Gonadotropin (HCG) test;Brain tumor (with mass effect);Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiencyKnown coagulopathy, INR>1.7 or use of novel anticoagulants < 48h from symptom onsetPlatelets < 50*109/L;Suspicion of septic emboli or endocarditisRenal Failure as defined by a serum creatinine > 2.5 mg/dl (or 220μmol/l) or glomerular Filtration Rate [GFR] < 30ml/min;Patient who requires hemodialysis or peritoneal dialysis, or who has a contraindication to angiogram for whatever reason;Suspicion of aortic dissection;Parenchymal organ surgery and biopsy were performed in the past one month;Any active bleeding or recent bleeding (gastrointestinal bleeding, urinary bleeding, etc.) in the past 1 month;History of life-threatening allergy (more than rash) to contrast medium;SBP >185 mmHg or DBP >110 mmHg refractory to treatment;Serious, advanced, terminal illness with anticipated life expectancy < 6 months;Participation in another randomized clinical trial that could confound the evaluation of the study;Other circumstances that the investigator considers inappropriate for participation or may pose a significant risk to patients (e.g. inability to understand and/or comply with study procedures and/or follow-up due to mental disorders, cognitive or mood disorders).Specific Neuroimaging Exclusion CriteriaMidline shift or herniation, mass effect with effacement of the ventriclesEvidence of acute intracranial hemorrhage on CT/MRIAcute bilateral strokes or multiple intracranial vessel occlusionsIsolated extracranial ICA occlusion or tandem carotid / MCA occlusionDissection of occluded artery on DSA after thrombectomy