Intravenous Thrombolysis With rhTNK-tPA for Acute Non-large Vessel Occlusion in Extended Time Window

Inclusion Criteria: * Clinical diagnosis of acute ischemic stroke * Age≥18 years * Pre-stroke mRS score≤1 points * Disabling stroke defined as follows: * Baseline NIHSS score 6-25 at the time of randomization, * Or NIHSS 4-5 with disabling deficit (e.g. hemianopia, aphasia, loss of hand function) as determined by the managing clinician * Onset (last-seen-well) time to treatment time between 4.5 and 24 hours * Written informed consent from patients or legally responsible representatives * The presence of a Target Mismatch on CT perfusion: ischemic core volume\<50ml (defined as rCBF\<30%), mismatch ratio≥1.2 (Tmax\>6 sec lesion/core volume lesion), mismatch volume≥10ml Exclusion Criteria: * Treatment with a thrombolytic within the last 72 hours or intention to receive intravenous thrombolysis * Contraindication to thrombolysis * Planned or anticipated treatment with endovascular therapy * Rapidly improving symptoms, particularly if in the judgment of the managing clinician that the improvement is likely to result in a NIHSS score\<4 at randomization * Pregnancy or lactating; formal testing needed in women of childbearing potential * Brain tumor (with mass effect) * Hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency * Impairment in coagulation due to comorbid disease or anticoagulant use. If on warfarin, international normalized ratio (INR) \>1.7 or prothrombin time \>15s; if use of any direct oral anticoagulant within the last 48 hours; if use of heparin/heparinoid within the last 24 hours * Use of glycoprotein Ⅱb-Ⅲa inhibitors within the last 72 hours * Baseline platelet count \<100,000/μL * Undergoing hemodialysis or peritoneal dialysis; known severe renal insufficiency with glomerular filtration rate \<30ml/min or serum creatinine \>220mmol/L (2.5mg/dl) * Suspected aortic dissection * Major surgery or biopsy within the last 1 month * Any active bleeding within the previous 1 month (including gastrointestinal or urinary bleeding) * Known severe, life-threatening allergy (more severe than skin rash) to contrast agents * Severe, uncontrolled hypertension (systolic blood pressure \>185mmHg or diastolic blood pressure \>110mmHg) * Any terminal illness such that the patient would not be expected to survive more than half a year * Current participation in any investigational study that may confound outcome assessment of the study * Any condition that, in the judgement of the investigator, is inappropriate for participation in the trial or could impose hazards to the patient (e.g. inability to understand and/or follow the study procedures and/or follow-up due to mental disorders, cognitive or emotional disorders) Specific Neuroimaging Exclusion Criteria: * Evidence of acute intracranial hemorrhage * Acute large vessel occlusion on magnetic resonance/ computed tomography angiography, including internal carotid artery (ICA), middle cerebral artery M1 segment (MCA-M1）, vertebral artery and basilar artery