A phase III, multicentre, prospective, randomised, open-label, blinded-endpoint clinical trial will evaluate two thrombolytic agents for the treatment of acute large vessel occlusion stroke within 4.5 hours from symptoms onset: intravenous tenecteplase bridging mechanical thrombectomy vs. intravenous alteplase bridging mechanical thrombectomy.

Efficacy and Safety of Tenecteplase Bridging Mechanical Thrombectomy for Acute Large Vessel Occlusive Stroke(TNK-LVO) is a phase III, multicenter, prospective, randomized, open-label, blinded-endpoint clinical trial. Randomization will be 1:1 according to reperfusion treatment modalities: (A) Intravenous thrombolysis with tenecteplase (0.25 mg/kg) plus mechanical thrombectomy vs. (B) Intravenous thrombolysis with alteplase (0.9 mg/kg) plus mechanical thrombectomy. For the primary outcome, the subjects will be followed up within 90 days after randomization. The primary outcome will be the Functional independence defined as modified Rankin Score ≤ 2.

Inclusion Criteria:

1. Age is ≥18 years.
2. AIS symptom onset ≤4.5 hours, onset time refers to the time the patient was last known to be well. (Recommendation time from thrombolysis to puncture within 60 minutes).
3. Arterial occlusion of the internal carotid artery (ICA), anterior cerebral artery (ACA), posterior cerebral artery (PCA), M1 or M2 segment of the middle cerebral artery (MCA), or basilar artery on computed tomography angiography (CTA) or magnetic resonance angiography (MRA).
4. Prestroke mRS score ≤2.
5. Informed consent from the patient or legally authorised representative.

Exclusion Criteria:

1. Patients diagnosed with hemorrhagic stroke (including intraparenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/extradural hematoma, etc.) or other related conditions identified by CT.
2. Contraindication to imaging examinations involving contrast agent injection.
3. Patients presenting with clinical symptoms of coma (NIHSS Score Item 1a = 3).
4. History of intracranial hemorrhage.
5. History of severe head trauma or stroke within the past 3 months.
6. Intracranial or intraspinal surgery within the past 3 months.
7. Major surgery within the past 2 weeks.
8. Gastrointestinal or urinary tract bleeding within the past 3 weeks.
9. Intracranial tumor, arteriovenous malformation, or giant intracranial aneurysm.
10. Active visceral bleeding.
11. Aortic arch dissection.
12. Arterial puncture at a non-compressible site within the past week.
13. Uncontrolled hypertension despite active antihypertensive treatment: Systolic Blood Pressure > 180 mmHg or Diastolic Blood Pressure > 100 mmHg.
14. Acute hemorrhagic tendency, including platelet count < 100 × 10⁹/L or other conditions.
15. Heparin treatment received within the past 24 hours.
16. For patients on oral anticoagulants: INR > 1.7 or PT > 15 seconds.
17. Use of direct thrombin inhibitors or direct Factor Xa inhibitors within the past 48 hours.
18. Blood glucose < 2.8 mmol/L or > 22.2 mmol/L.
19. Hypodensity affecting > 1/3 of the middle cerebral artery territory or an equivalent proportion of the basilar artery territory on non-contrast CT.
20. Rapidly improving symptoms as determined by the investigator.
21. Participation as a subject in another research study within the past 30 days.
22. Any terminal illness where life expectancy is considered not to exceed 1 year.
23. Any condition where, in the judgment of the investigator, the study treatment might pose a risk to the patient or affect the patient's participation in the study.
24. Pregnant women.
25. Known allergy to the active ingredients (Alteplase, Tenecteplase) or any excipients.