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

Inclusion Criteria: The clinical diagnosis is acute ischemic stroke (the criteria followed the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018). Age≥18 years Pre-stroke mRS score≤1 points Baseline NIHSS 4-25 (both included) at the time of randomization Onset (last-seen-well) time to treatment time between 4.5 and 24 hours Informed consent from the patient or surrogate 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: Treated with intravenous thrombolysis within 72 hours Have a clear contraindication for intravenous thrombolysis Intended to proceed endovascular treatment 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 Woman of childbearing potential who is known to be pregnant or who has a positive pregnancy test on admission Brain tumor (with mass effect) Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency Coagulation Disorders caused by diseases or anticoagulants: warfarin was used with International Normalized Ratio (INR)>1.7 or PT>15s; heparin was administered within 24 hours; novel oral anticoagulants were used within 48 hours Glycoprotein IIb-IIIa inhibitors were used within the past 72 hours Baseline platelet count <100×109/L Known severe renal insufficiency with eGFR<30ml/min or serum creatinine>2.5mg/dl Undergoing hemodialysis or peritoneal dialysis; known severe intolerance to contrast media Suspected aortic dissection Parenchymal organ surgery or biopsy within the previous 1 month Any active bleeding within the previous 1 month (including gastrointestinal or urinary bleeding) Known severe allergy (more than a rash) to contrast media uncontrolled by medications Refractory hypertension (defined as persistent systolic blood pressure>185mmHg or diastolic blood pressure>110mmHg) Expected survival time<0.5 year (such as complicated with malignant tumor, serious heart and lung diseases, etc.) Participants in other interventional randomized trials that may confound the outcome assessment Other circumstances that the investigator considers inappropriate for participation in the trial or that may pose significant risks to patients (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 Presence of proximal arterial occlusion on CTA/MRA (e.g., intracranial ICA, MCA-M1 and dominant M2 segments, and vertebrobasilar arteries) Ischemic core volume>1/3 of the MCA territory defined on CT/MRI