Tenecteplase for Late-Window Stroke Guided by DWI-FLAIR Mismatch

The goal of this clinical trial is to evaluate the efficacy and safety of tenecteplase administered 4.5-9 hours after stroke onset (defined as the time the patient was first found with symptoms, including wake-up stroke and unwitnessed stroke) in patients with acute ischemic stroke (AIS) guided by DWI-FLAIR mismatch on MRI. The main questions it aims to answer are: 1. Does tenecteplase improve functional outcomes at 90 days compared with standard treatments in AIS patients administered 4.5-9 hours after stroke onset guided by DWI-FLAIR mismatch? 2. The safety of tenecteplase thrombolysis for AIS patients in the 4.5-9 hours guided by DWI-FLAIR mismatch. Researchers will compare tenecteplase to placebo to see if it is effective and safe for these patients. Participants will be randomly assigned (1:1) immediately after randomization: * Tenecteplase group: received tenecteplase, intravenously as a bolus administered over a period of 5 to 10 seconds at a dose of 0.25 mg per kilogram (maximum dose, 25 mg), plus aspirin placebo (300 mg). * Control group: aspirin (300 mg) plus tenecteplase placebo. From day 2 to day 90, all patients will be conformed to the 2023 Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke.

Inclusion Criteria: 1. Age ≥ 18 years; 2. AIS with symptom onset 4.5-9 hours before enrollment, including wake-up stroke and unwitnessed stroke (onset time defined as when symptoms were first noticed); 3. Imaging criteria: 1. DWI-FLAIR mismatch: visible lesion on DWI with no marked visible lesion on FLAIR; 2. DWI infarct core not exceeding one-third of the middle cerebral artery territory, one-half of the anterior cerebral artery territory, or one-half of the posterior cerebral artery territory; 4. NIHSS score 4-25; 5. First-ever stroke or previous stroke without significant disability (pre-stroke mRS ≤ 1); 6. Signed informed consent from the patient or legally authorized representative. Exclusion Criteria: 1. Planned endovascular treatment; 2. Contradictory to MRI examination; 3. MRI image not qualified for evaluation; 4. Obvious head injuries or strokes within 3 months; 5. Subarachnoid or intracranial hemorrhage; 6. History of intracranial hemorrhage; 7. Intracranial tumor, arteriovenous malformation or aneurysm; 8. Intracranial or spinal cord surgery within 3 months; 9. Active internal hemorrhage; 10. platelet count of \1.6 or APTT abnormal; 14. Oral anticoagulation therapy; 15. Systolic pressure≥185 mmHg or diastolic pressure≥110 mmHg; 16. Blood glucose \< 50 mg/dl (2.7mmol/L); 17. Pregnancy; 18. Neurological deficit after epileptic seizures; 19. Major surgery within 1 month; 20. Gastrointestinal or urinary tract hemorrhage within the previous 30 days; 21. Myocardial infarction within 3 months; 22. Allergy to study drugs; 23. Unlikely to adhere to the trial protocol or follow-up; 24. Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study; 25. Participation in other interventional clinical trials within the previous 3 months.