Endovascular Treatment With or Without Preceding Intravenous Tenecteplase (TNK) in Patients With Late-window acUte Ischemic Stroke Due to Middle Cerebral Artery Occlusion

Prior treatment

• Patients who decline interventional therapy or intravenous thrombolysis (IVT)；
• Active internal bleeding or at high risk of bleeding, e.g.: Major surgery, trauma or gastrointestinal or urinary tract haemorrhage within the previous 21 days, or arterial puncture at a non-compressible site within the previous 7 days；
• Ischemic stroke or myocardial infarction in previous 3 months, previous intracranial hemorrhage, severe traumatic brain injury, intracranial or intraspinal operation in previous 3 months, or known intracranial neoplasm (excluding neuroectodermal tumors such as meningioma), arteriovenous malformation or giant aneurysm；
• Participation in any other interventional clinical trials within the previous 3 months.

Other illness

• Patients allergic to tenecteplase；
• NIHSS consciousness score 1a\>2, or epileptic seizure, hemiplegia after seizures or combined with other nervous/mental illness not able to cooperate or unwilling to cooperate；
• Acute or past intracerebral hemorrhage (ICH) identified by CT or MRI, including cerebral parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid haemorrhage, and subdural / extradural hematoma；
• Any condition that, in the investigator's judgment, could pose a hazard to the patient if study therapy is initiated or could impact the patient's ability to participate in the study；

Lab values

• Blood glucose \< 2.8 or \> 22.2 mmol/L (point of care glucose testing is acceptable)；
• Any known impairment in coagulation, e.g.: If on vitamin K antagonists, then INR \>1.7 or prothrombin time \>15 seconds; if use of any direct thrombin inhibitors or new oral anticoagulants (NOACs) during the last 48 hours unless reversal of effect can be achieved with idarucizumab; values in sensitivity laboratory tests exceed the upper limit of normal \[including activated partial thromboplastin time (APTT), international normalized ratio (INR), platelet count, thrombin time (TT), or appropriate factor Xa activity assays, etc.\]; if on heparin during the last 24 hours or with an elevated aPTT greater than the upper limit of normal；
• Known defect of platelet function or platelet count below 100\*109/L (patients on antiplatelet agents can be included)；

Other

• Rapidly improving symptoms at the discretion of the investigators；
• Persistent blood pressure elevation (systolic \> 185 mmHg or diastolic \>110 mmHg), despite blood pressure lowering treatment；
• Patients who would not be expected to survive more than 1 year；
• Unable to perform CTP or MRP；
• Large infarct on non-contrast CT brain or MRI (infarct size \>1/3 MCA territory)；
• Multiple arterial occlusions (bilateral MCA occlusion, MCA occlusion accompanied by basilar artery occlusion)；
• Pregnant women, nursing mothers, or reluctant to take contraceptive measures during the trial period；
• Unlikely to adhere to the trial protocol or follow-up；

• Age≥18 years old;
• Acute ischemic stroke symptom onset between 4.5 to 24 hours prior to enrollment including wake-up stroke and unwitnessed stroke; onset time refers to 'last seen well time';
• MCA-M1 or proximal M2 occlusions confirmed by Computer Tomography Angiography (CTA)/Magnetic Resonance Angiography (MRA) that was responsible for signs and symptoms of acute ischemic stroke;
• Neuroimaging: target mismatch profile on CT perfusion (CTP) or MRI + MR perfusion imaging (MRP) (analyzed by perfusion analysis software with Class II and above medical device certificates) \[ischemic core volume (defined as CBF\<30% or apparent diffusion coefficient value \< 620×10-6 mm2/s) \<70mL, mismatch ratio≥1.8, mismatch volume≥15mL\];
• Pre-morbid mRS score ≤2;
• Baseline NIHSS 6-25 (both included);
• Written informed consent from patients or their legally authorized representative.