Tenecteplase in ReperfUsion Therapy for Posterior Circulation Stroke With Extended Time Window: the TRUST Trial

Inclusion Criteria: 1. Patients presenting with clinical signs of acute ischemic stroke between 4.5 and 24 hours from stroke onset, or wake-up stroke and unwitnessed stroke (if the midpoint of the last known well time is within 4.5 to 24 hours) 2. Patients aged \> 18 years (or as per local requirements) 3. NIHSS ≥ 4 4. Patients with a posterior circulation ASPECT score (PC-ASPECTS) ≥ 7. If MRI is performed first and the PC-ASPECTS on diffusion-weighted imaging (DWI) is ≥ 7, a non-contrast head CT is not required. If PCASPECTS on DWI is \< 7, the subsequent non-contrast CT must show a PC-ASPECTS ≥ 7 for inclusion 5. Posterior circulation stroke confirmation criteria: If MRI is performed, infarction confirmed by DWI is sufficient. If CT is performed, the non-contrast CT scan must not refute posterior circulation stroke, and clinical signs and symptoms must support the diagnosis, as confirmed by experienced clinicians. If clinical symptoms are atypical, CTA showing symptomatic stenosis or occlusion of large posterior circulation vessels, or CT perfusion showing symptomatic hypoperfusion, can provide additional evidence, though advanced imaging is not mandatory 6. Pre-stroke mRS score \< 2 7. Informed consent has been obtained from the patient, a family member, or a legally responsible person, depending on local ethics requirements Exclusion Criteria: 1. Contraindications for tenecteplase: * Allergy to tenecteplase * Rapidly improving symptoms at the discretion of the investigator * The presence of epileptic seizures, hemiplegia after seizures (Todd's palsy), or other neurological/mental illnesses that prevent cooperation or willingness to participate * Persistent blood pressure elevation (systolic ≥180 mmHg or diastolic ≥100 mmHg) despite treatment * Blood glucose levels outside the acceptable range (\<2.8 mmol/L or \>22.2 mmol/L), with point-of-care glucose testing considered valid * High risk of bleeding due to active internal bleeding, major surgery, trauma, gastrointestinal, or urinary tract hemorrhage within the previous 21 days, or arterial puncture at a non-compressible site within the previous 7 days * Known impairments in coagulation due to comorbid disease or anticoagulant use, including an INR \>1.7 or prothrombin time \>15 seconds for those on warfarin, recent use of direct thrombin inhibitors or direct factor Xa inhibitors without reversal capability, or full-dose heparin/heparinoid within the last 24 hours with an aPTT above normal limits * Known defect in platelet function or a platelet count below 100,000/mm³ * History of ischemic stroke, myocardial infarction, intracranial hemorrhage, severe traumatic brain injury, or intraspinal operation within the previous 3 months, or known intracranial neoplasm, arteriovenous malformation, or giant aneurysm * Acute or past intracerebral hemorrhage identified by CT or MRI 2. Infarction of the anterior circulation confirmed by MRI, or vascular examination indicating occlusion of large anterior circulation vessels, or perfusion imaging showing hypoperfusion changes in the anterior circulation area 3. Pregnancy, nursing, or unwillingness to use effective contraceptive measures during the trial period 4. Likelihood of non-adherence to the trial protocol or follow-up 5. Any condition that, in the judgment of the investigator, could impose hazards if study therapy is initiated or affect patient participation in the study 6. Participation in other interventional clinical trials within the previous 3 months 7. A life expectancy of less than three months 8. The judgment is left to the discretion of the investigator