Post-thrombectomy Intra-arterial Tenecteplase for Acute manaGement of Non-retrievable Thrombus and No-reflow in Emergent Stroke

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.