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

Inclusion Criteria:

1. Age≥18 years old.

2. Acute ischemic stroke symptom onset between 4.5 to 24 hours prior to enrollmentincluding wake-up stroke and unwitnessed stroke; Onset time refers to 'last seenwell time'.

3. MCA-M1 or M2 occlusions confirmed by Computer Tomography Angiography (CTA)/MagneticResonance Angiography (MRA) that was responsible for signs and symptoms of acuteischemic stroke.

4. Neuroimaging: target mismatch profile on CT perfusion (CTP) or MRI + perfusionweighted imaging (PWI) (analyzed by perfusion analysis software with Class II andabove medical device certificates) [ischemic core volume (defined as CBF<30%) <70mL,mismatch ratio≥1.8, mismatch volume≥15mL].

5. Pre-stroke 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 Recombinant Human TNK Tissue-type Plasminogen Activator forInjection (rhTNK-tPA).

3. Rapidly improving symptoms at the discretion of the investigators.

4. NIHSS consciousness score 1a>2, or epileptic seizure, hemiplegia after seizures orcombined with other nervous/mental illness not able to cooperate or unwilling tocooperate.

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 (on random glucose testing is acceptable).

7. Active internal bleeding or at high risk of bleeding, e.g.: Major surgery, trauma orgastrointestinal or urinary tract hemorrhage within the previous 21 days, orarterial 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>1.7or prothrombin time >15 seconds; if use of any direct thrombin inhibitors or neworal anticoagulants (NOACs) during the last 48 hours unless reversal of effect canbe achieved with idarucizumab; values in sensitivity laboratory tests exceed theupper limit of normal [including activated partial thromboplastin time (aPTT),international normalized ratio (INR), platelet count, thrombin time (TT), orappropriate factor Xa activity assays, etc.]; if on heparin during the last 24 hoursor 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 onantiplatelet agents can be included).

10. Ischemic stroke or myocardial infarction in previous 3 months, previous intracranialhemorrhage, severe traumatic brain injury, intracranial or intraspinal operation inprevious 3 months, or known intracranial neoplasm (neuroectodermal tumor excludedlike 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 PWI.

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, includingcerebral parenchymal hemorrhage, intraventricular hemorrhage, subarachnoidhemorrhage, and subdural/extradural hematoma.

15. Multiple arterial occlusions (bilateral MCA occlusion, MCA occlusion accompanied bybasilar artery occlusion).

16. Pregnant women, nursing mothers, or reluctant to take contraceptive measures duringthe 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 thepatient if study therapy is initiated or could impact the patient's ability toparticipate in the study.

19. Participation in any other interventional clinical trials within the previous 3months.