The purpose of this study is to determine the safety and feasibility of using intra-arterial Tenecteplase in patients undergoing blood clot extraction for treatment of acute ischemic (non-bleeding) stroke. Intravenous Tenecteplase is FDA-approved to treat patients with an ischemic stroke presenting within the 0-3-hour time window.

The primary objective of this study is to determine the safety and feasibility of intra-arterial Tenecteplase in selected patients with persistent post-thrombectomy hypoperfusion on computed tomography perfusion based on symptomatic intracranial hemorrhage (parenchymal hematoma type 2, subarachnoid hemorrhage, and/or intraventricular hemorrhage producing decline from the initial NIHSS of ≥ 4 points) at 24-36 hours.

Inclusion Criteria:

• Patient/legally authorized representative has signed the Informed Consent Form
• Ability to comply with the study protocol, in the investigator's judgment
• Functionally independent (modified Rankin scale 0-2) prior to presentation
• Baseline National Institutes of Health Stroke Scale (NIHSS) ≥ 6
• Clinical syndrome consistent with occlusion of the internal carotid artery (ICA) or proximal middle cerebral artery (MCA), presenting within 4.5- to 24-hours of TLKW
• Evidence of ICA, MCA-M1, or MCA-M2 occlusion on baseline computed tomography angiogram (CTA) or magnetic resonance angiogram (MRA). ICA/MCA tandem occlusions may be enrolled
• Alberta Stroke Program Early Computed Tomography Score ≥ 6 on pre-thrombectomy unenhanced CT as determined by treating neurologist or reading radiologist
• Pre-thrombectomy CTP or MRP with core infarction (cerebral blood flow < 30%) < 70 ml, mismatch ratio ≥ 1.8, mismatch volume ≥ 15 ml (completed within 120 minutes of skin puncture for thrombectomy). If skin puncture occurs more than 120 minutes after the pre-thrombectomy CTP, enrollment may proceed at the PI's discretion.
• Endovascular thrombectomy of ICA, MCA-M1 or MCA-M2 occlusion performed according to local standard of care, defined as at least completing the initial diagnostic angiogram
• CTP performed with RAPID AI AngioFlowTM within 30 minutes of thrombectomy completion
• Modified thrombolysis in cerebral infarction (mTICI) 2b-3 revascularization following endovascular thrombectomy (EVT) (or after initial diagnostic angiogram)
• Presence of Tm > 6 lesion on post-EVT CTP of adequate quality for interpretation in the distribution of the symptomatic occlusion

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 (e.g., Alzheimer's patients taking lecanemab)
• Systolic blood pressure > 185 mm Hg or diastolic blood pressure > 110 mm Hg after EVT, refractory to medical therapy
• 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
• Baseline platelet count < 100,000/mcL (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
• Intracranial malignant neoplasm, arteriovenous malformation, or unsecured aneurysm > 1 cm
• 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
• Acute intracranial hemorrhage on pre-thrombectomy imaging or suspected acute intracranial hemorrhage after EVT
• Acute bilateral strokes on initial imaging
• Multiple acute intracranial occlusions (except ICA/MCA) on initial CTA or MRA
• Significant hemispheric mass effect or any amount of midline shift due to acute stroke
• Placement of cervical carotid or intracranial stent during thrombectomy procedure requiring dual antiplatelet therapy