The purpose of this study is to investigate the safety and efficacy of endovascular treatment with or without preceding intravenous Tenecteplase in patients with late-window (4.5-24 hours of symptom onset) acute ischemic stroke due to middle cerebral artery (MCA) M1 or proximal M2 occlusion.

After being informed about the study and potential risks, patients who meet the inclusion criteria will be randomized to endovascular treatment with preceding intravenous Tenecteplase (0.25mg/kg, maximum 25mg) or without preceding intravenous Tenecteplase in a 1:1 ratio. Written informed consent will be needed.

Inclusion criteria

1. Age≥18 years old;
2. 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';
3. 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;
4. 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];
5. Pre-morbid mRS score ≤2;
6. Baseline NIHSS 6-25 (both included);
7. Written informed consent from patients or their legally authorized representative.

Exclusion criteria

1. Patients who decline interventional therapy or intravenous thrombolysis (IVT)；
2. Patients allergic to tenecteplase；
3. Rapidly improving symptoms at the discretion of the investigators；
4. 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；
5. Persistent blood pressure elevation (systolic > 185 mmHg or diastolic >110 mmHg), despite blood pressure lowering treatment；
6. Blood glucose < 2.8 or > 22.2 mmol/L (point of care glucose testing is acceptable)；
7. 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；
8. 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；
9. Known defect of platelet function or platelet count below 100*109/L (patients on antiplatelet agents can be included)；
10. 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；
11. Patients who would not be expected to survive more than 1 year；
12. Unable to perform CTP or MRP；
13. Large infarct on non-contrast CT brain or MRI (infarct size >1/3 MCA territory)；
14. Acute or past intracerebral hemorrhage (ICH) identified by CT or MRI, including cerebral parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid haemorrhage, and subdural / extradural hematoma；
15. Multiple arterial occlusions (bilateral MCA occlusion, MCA occlusion accompanied by basilar artery occlusion)；
16. Pregnant women, nursing mothers, or reluctant to take contraceptive measures during the trial period；
17. Unlikely to adhere to the trial protocol or follow-up；
18. 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；
19. Participation in any other interventional clinical trials within the previous 3 months.

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