Multicentre, prospective, Multi-arm Multi-stage (MAMS) seamless phase 2b/3 interventional randomized placebo-controlled double-blinded parallel-assignment (2 arms with 1:1 randomization) efficacy and safety trial to test intra-arterial tenecteplase at the completion of thrombectomy versus best practice in participants with anterior circulation LVO receiving mechanical thrombectomy within 24 hours of symptoms onset.

Inclusion Criteria:

• Adult participants (age≥18 years) presenting with ischemic stroke with arterial LVO on CT/MR Angiogram of the intracranial internal carotid or middle cerebral artery (MCA) first segment (M1) or proximal second segment (M2) committed to thrombectomy using standard criteria within 24 hours of onset:
• For 0-6 hours of symptom onset: Presence of arterial occlusion as defined above and ASPECTS≥3 on NCCT
• For 6-24 hours of symptom onset: Additional imaging criteria on CTP or MRI perfusion of core volume <100ml.
• Qualifying CT/MR within 4hrs of randomisation (repeat CT for transferred participants required if >4hr)
• Pre-stroke Modified Rankin Scale (mRS) score of ≤2 (mild pre-existing disability permitted)
• Local legal requirements for consent have been satisfied.

Exclusion Criteria:

• Intracranial hemorrhage identified by CT or MRI
• ASPECTS 0-2 on NCCT
• CTP or MRI perfusion ischemic core volume >100ml if presenting within 6-24 hours from symptoms onset
• Anticipated endovascular stenting required for intracranial or extracranial atherosclerotic stenosis/occlusion.
• More than six retrieval attempts in the same vessel
• Alteplase being infused within 30 minutes (~5x half-life) of anticipated trial drug administration
• Contraindication to imaging with contrast agents
• Any condition (eg.mid-arterial phase early venous filling) that in the judgment of investigators could impose hazards if study therapy is initiated
• Pregnant women.
• Current participation in another intervention research study that includes experimental interventions beyond standard-of-care.
• Anticoagulation. INR ≤1.7 if on warfarin, and dabigatran reversal by idarucizumab are permitted.
• Other standard contraindications to thrombolysis apart from time window.
• Known terminal illness such that the participants would not be expected to survive a year.
• Planned withdrawal of care or comfort care measures.