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 computed tomography perfusion (CTP) or magnetic resonance perfusion (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)
* 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