Efficacy and Safety of Tenecteplase Bridging Mechanical Thrombectomy for Acute Large Vessel Occlusion Stroke

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.

Eligibility Criteria:
Inclusion Criteria:

1. Age is 18-80 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 on CTA of the ICA, ACA, PCA, M1, M2 or basilar.
4. Prestroke mRS score ≤2.
5. Informed consent from the patient or legally authorised representative.

Exclusion Criteria:

1. ICH, subarachnoid haemorrhage or other brain haemorrhage identified by CT.
2. NIHSS consciousness score (NIHSS 1a) \>2.
3. Contraindication to imaging with contrast agents.
4. Intraventricular haemorrhage, subarachnoid haemorrhage, subdural/external haematoma, etc) in previous 3 months.
5. Severe brain trauma or ischaemic stroke in previous 3 months.
6. Intracranial or intraspinal surgery in previous 3 months.
7. Major surgery within the previous 14 days.
8. Gastrointestinal or urinary tract haemorrhage within the previous 21 days.
9. Known malignant intracranial neoplasm, giant intracranial aneurysm or arteriovenous malformation.
10. Known active visceral bleeding.
11. Known aortic arch dissection.
12. Arterial puncture at a non-compressible site within the previous 7 days.
13. Persistent blood pressure elevation (systolic ≥180 mm Hg or diastolic ≥100 mm Hg), despite blood pressure lowering treatment.
14. Known defect of platelet or clotting function, platelet count below 100×109/L (note that patients on antiplatelet agents can be included).
15. Use of heparins during the last 48 hours.
16. Any known defect in coagulation, for example, current use of oral warfarin anticoagulant with an international normalised ratio \>1.7 or prothrombin time \>15 s.
17. Use of direct thrombin inhibitors or direct factor Xa inhibitors during the last 48 hours.
18. Blood glucose \<2.8 mmol/L or \>22.22 mmol/L (point-of-care glucose testing is acceptable).
19. Hypodensity in \>1/3 middle cerebral artery territory on non-contrast computer tomography (NCCT).
20. Rapidly improving symptoms at the discretion of the investigator.
21. Participation in another clinical trial within the previous 3 months.
22. Any terminal illness such that patient would not be expected to survive \>1 year.