Prospective, single center, non-randomized, pilot study to assess the feasibility of IA TNK following standard of care mechanical thrombectomy (MT) in patients with AIS. Participants will receive IA TNK after achieving mTICI 2b or 2c reperfusion with standard of care MT. Patients enrolled into the study will be followed for 3 months after treatment with IA TNK.

As current MT technology is not amenable to retrieval of distal occlusions (M3/M4, etc), we hypothesize that IA lytic may play an important role as an adjunctive therapy to open up distal vessels (after the primary LVO has been removed) to achieve complete or near complete reperfusion. In this pilot trial, our goal is to assess the feasibility and safety of IA Tenecteplase (TNK) as an adjunctive therapy following standard of care mechanical thrombectomy (MT) in patients with AIS. A total of 20 patients will be enrolled into the ALLY pilot study.

Inclusion Criteria:

• 1. Age 18-85
• 2. Anterior circulation ischemic stroke symptoms with confirmed occlusion (ICA, M1, or M2) on angiogram and mechanical thrombectomy initiated within 24 hours since last known well
• 3. a. Patients treated less than 6 hours since last known well with ASPECTS >6. b. Patients treated beyond 6 hours since last known well, CT or MRI perfusion scan showing favorable mismatch profile (Target mismatch profile on CT perfusion or MRI (ischemic core volume is <70ml, mismatch ratio is >1.8 and mismatch volume is >15ml)
• 4. Post-mechanical thrombectomy with ≤5 device passes and mTICI grade 2b or 2c with persistent occlusion(s) in terminal branches not amenable to MT.
• 5. Signed informed consent

Exclusion Criteria:

• 1. Premorbid modified Rankin scale (mRS) score of 4 or greater
• 2. Presence of any hemorrhage and/or ASPECT score ≤6 on baseline head CT
• 3. Platelet count <100,000
• 4. Known bleeding diathesis
• 5. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency
• 6. Active anticoagulation treatment with novel oral anticoagulant (NOACs) taken within the last 48 hours, or INR >1.8
• 7. Patients requiring active treatment with dual antiplatelet agents (e.g. proximal cervical carotid artery stenting)
• 8. Pregnant or lactating
• 9. Previous known allergy to TNK
• 10. Major surgery in past 30 days
• 11. Patient is on or requires dialysis
• 12. History of intracranial hemorrhage or serious head trauma at any time
• 13. Any condition in the opinion of the enrolling physician that would preclude the patient from participating
• 14. Pre-existing medical, neurological, or psychiatric disease that would confound the neurological or functional evaluation
• 15. Severe, uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) that is refractory to treatment
• 16. History of acute ischemic stroke in the last 60 days
• 17. Presumed septic embolus; suspicion of bacterial endocarditis
• 18. Suspicion of aortic dissection
• 19. Intracranial neoplasm
• 20. Any mass effect
• 21. Any terminal medical condition with life expectancy less than 6 months
• 22. Concurrent enrollment in another trial that could confound the results of this study