This study will address the efficacy and safety of Tenecteplase administered in non-endovascular capable center (nECC) in patients with acute ischemic stroke (AIS) caused by anterior circulation large vessel occlusion (acLVO) who present in the 4.5- to 24-hour time window before interhospital transfer to an endovascular capable center (ECC) for endovascular treatment (EVT).

• Primary objective: To evaluate the efficacy and safety of Tenecteplase administration at a nECC before EVT transfer compared with standard of care
• Secondary objective: To evaluate the impact of time from needle-to-arterial puncture on clinical outcomes Patients who meet inclusion criteria will be randomized to Tenecteplase (0.25mg/kg, maximum 25mg) before transfer or standard of care. A single bolus dose should be injected over 5 seconds.

Inclusion Criteria:

• Age of 18 years or older;
• AIS symptom onset to treatment initiation within 4.5 to 24 hours, stroke onset is defined as the time the patient was last known to be well (including wake-up stroke and unwitnessed stroke);
• Signs and symptoms consistent with the diagnosis of an acute anterior circulation ischemic stroke involving occlusion of the internal carotid artery (ICA), MCA (M1 or M2) vessels;
• Functionally independent (mRS 0-2) prior to stroke onset;
• Baseline National Institute of Health Stroke Scale (NIHSS) of 6-25;
• Intended to transfer to ECCs for EVT (patient transfer), or intended to transfer a neurointerventionalist from the ECC for EVT (physician transfer);
• Written informed consent from patients or legally authorized representatives;
• Neuroimaging: ICA or M1, M2 occlusion by MRA or CTA AND the target mismatch profile on computed tomography perfusion (CTP) or magnetic resonance perfusion (MRP), defined as an ischemic core volume <70mL, mismatch volume ≥15mL and mismatch ratio ≥1.8;

Alternative neuroimaging (if CTP or MRP is technically inadequate or unavailable):

The presence of a diffusion-weighted imaging (DWI)-fluid-attenuated inversion recovery (FLAIR) mismatch pattern (i.e., acute ischemic lesion visible on DWI but no marked parenchymal hyperintensity visible on FLAIR) OR an Alberta Stroke Program Early CT Score (ASPECTS) score ≥7 on NCCT or MRI scan;

Exclusion Criteria:

• Known hypersensitivity or allergy to any ingredients of Tenecteplase;
• Intended to receive IVT as standard-of-care therapy;
• Rapidly improving symptoms with NIHSS score <6 before randomization;
• Any contra-indication for IVT except for the time criterion;
• Known hereditary or acquired hemorrhagic diathesis;
• Impairment in coagulation due to comorbid disease or anticoagulant use. If on warfarin, INR >1.7 or prothrombin time >15s; if use of any direct oral anticoagulant within the last 48 hours; if on any full dose heparin/heparinoid within the last 24 hours;
• Ischemic stroke or myocardial infarction in previous 3 months
• Previous intracranial hemorrhage, active internal bleeding (gastrointestinal or urinary tract hemorrhage) in previous 3 months;
• Severe, uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg);
• Other serious, advanced or terminal illness with life expectancy less than 6 months;
• Baseline blood glucose <50mg/dl or >400mg/dl;
• Contraindication to imaging with contrast agents;
• Acute symptomatic arterial occlusions in more than one vascular territory confirmed on CTA or MRA (e.g. bilateral MCA occlusions, or an MCA and a basilar artery occlusion);
• Extensive early ischemic change on non-contrast CT or MRI-DWI estimated to be >1/3 MCA territory, or significant hypodensity outside the Tmax>6s perfusion lesion that invalidates mismatch criteria (if patient is enrolled based on CT perfusion criteria);
• Evidence of intracranial tumor (mass effect), acute intracranial hemorrhage, or arteriovenous malformation;
• Current participation in another investigational drug or device study;
• Suspected endocarditis;
• Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study;

According to Chinese laws and regulations, the IPD will not be shared.

Each ECC/nECC will designate one or more physician(s) to perform the follow-up evaluation at 24 (±12) hours, 7 (±2) days or discharge if earlier who cannot be involved in care of the subjects and must remain blinded to treatment assignment. Blinded assessors must undergo a standardized training and competency validation before delegated by the site principal investigator (PI).

Assessment of the primary outcome on the mRS at 90 (±7) days will be performed by a qualified neurologist via structured telephone interview, blinded to both the allocated and actually received treatment. All telephone interviews will be recorded by audio and formed into follow-up reports, which will then be centrally assessed by two experienced and certified physicians. For cases with disagreement between the two assessors, decisions are made by the third experienced neurologist.