EXtending the Time Window for Thrombolysis in Posterior Circulation Stroke Without Early CT Signs

Inclusion Criteria:

1. Patients presenting with clinical signs of acute ischemic stroke between 4.5 and 24hours from stroke onset, or wake-up stroke and unwitnessed stroke (if the midpointof the last known well time is within 4.5 to 24 hours)

2. Patients aged > 18 years (or as per local requirements)

3. NIHSS ≥ 1

4. Patients with a posterior circulation ASPECT score (PC-ASPECTS) ≥ 7. If MRI isperformed first and the PC-ASPECTS on diffusion-weighted imaging (DWI) is ≥ 7, anon-contrast head CT is not required. If PCASPECTS on DWI is < 7, the subsequentnon-contrast CT must show a PC-ASPECTS ≥ 7 for inclusion

5. Posterior circulation stroke confirmation criteria: If MRI is performed, infarctionconfirmed by DWI is sufficient. If CT is performed, the non-contrast CT scan mustnot refute posterior circulation stroke, and clinical signs and symptoms mustsupport the diagnosis, as confirmed by experienced clinicians. If clinical symptomsare atypical, CTA showing symptomatic stenosis or occlusion of large posteriorcirculation vessels, or CT perfusion showing symptomatic hypoperfusion, can provideadditional 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 legallyresponsible person, depending on local ethics requirements

Exclusion Criteria:

1. Intended to proceed to endovascular treatment

2. Contraindications for alteplase:

• Allergy to alteplase

• 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 willingnessto 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 >22.2mmol/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, orarterial 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 withoutreversal capability, or full-dose heparin/heparinoid within the last 24 hourswith 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 3months, or known intracranial neoplasm, arteriovenous malformation, or giantaneurysm

• Acute or past intracerebral hemorrhage identified by CT or MRI

3. Infarction of the anterior circulation confirmed by MRI, or vascular examinationindicating occlusion of large anterior circulation vessels, or perfusion imagingshowing hypoperfusion changes in the anterior circulation area

4. Pregnancy, nursing, or unwillingness to use effective contraceptive measures duringthe trial period

5. Likelihood of non-adherence to the trial protocol or follow-up

6. Any condition that, in the judgment of the investigator, could impose hazards ifstudy therapy is initiated or affect patient participation in the study

7. Participation in other interventional clinical trials within the previous 3 months

8. A life expectancy of less than three months

9. The judgment is left to the discretion of the investigator