Intra-arterial tenecteplase to improve small-vessel blood flow after mechanical clot removal

Inclusion Criteria:

* Patient/legally authorized representative has signed the Informed Consent Form
* At least 18 years of age
* Ability to comply with the study protocol, in the investigator's judgment
* Acute ischemic stroke attributed to anterior circulation large vessel occlusion (of the internal carotid artery or first segment of the middle cerebral artery based on CTA, MRA, or catheter angiogram) being treated with mechanical thrombectomy
* NIHSS ≥ 6 at the initiation of endovascular therapy (arterial puncture)
* Time from stroke onset to IA-TNK administration \< 24 hours. Stroke onset is defined as the time the patient was last known to be at their neurologic baseline
* ASPECTS ≥ 6 on pre-MT CT imaging
* If treated \> 6 hours from stroke onset, CTP imaging must demonstrates favorable mismatch profile (based on RAPID processing: infarct core \<70 mL, mismatch ratio ≥ 1.8 and mismatch volume ≥ 15 mL)
* Qualifying neuroimaging (CT and CTP, if applicable) must be obtained \<120 minutes prior to arterial puncture.

Exclusion Criteria:

* Current participation in another investigational drug or device study
* Known hypersensitivity or allergy to any ingredients of tenecteplase
* Active internal bleeding
* Known bleeding diathesis (Alzheimer's patients taking lecanemab)
* Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with INR \> 1.7
* Use of one of the new oral anticoagulants within the last 48 hours (dabigatran, rivaroxaban, apixaban, edoxaban)
* Treatment with a thrombolytic within the last 3 months prior to randomization, inclusive of intravenous thrombolysis during the index stroke.
* Baseline platelet count \< 100,000/microliter (results must be available prior to treatment)
* Baseline blood glucose \> 400 mg/dL (22.20 mmol/L)
* Baseline blood glucose \< 50 mg/dL needs to be normalized prior to randomization
* Intracranial or intraspinal surgery or trauma within 2 months
* Other serious, advanced, or terminal illness (investigator's judgment) or life expectancy is less than 6 months
* History of acute ischemic stroke in the last 90 days
* History of hemorrhagic stroke
* Presumed septic embolus; suspicion of bacterial endocarditis
* Any other condition that, in the opinion of the investigator, precludes an endovascular procedure or poses a significant hazard to the patient if an endovascular procedure was to be performed
* Pregnant
* Systolic BP \>185 mmHg or diastolic BP \>110 mmHg, refractory to treatment
* Suspicion of aortic dissection
* Known allergy to iodine or iodinated contrast
* Subject who requires hemodialysis or peritoneal dialysis, or who have a contraindication to an angiogram
* Renal failure as defined by a serum creatinine \> 3.0 mg/dl or GFR \< 30
* Known intracranial neoplasm
* GI bleeding within the past 21 days
* Pre-existing medical or neurological disease that will confound the neurological or functional evaluations
* Premorbid (prior to the index stroke) modified Rankin Scale (mRS) score ≥ 3

Additional neuroimaging exclusion criteria:

* ASPECTS \<6 on pre-MT CT imaging
* Acute intracranial hemorrhage or contrast extravasation on CT before or immediately after MT (prior to study drug administration)
* Significant mass effect with midline shift on non-contrast CT before or immediately after MT
* Cervical or intracranial stent placement during endovascular therapy
* Acute symptomatic arterial occlusions in more than one vascular territory confirmed on CTA, MRA, or catheter angiography