24 Hours Treatment with Alteplase in Patients with Ischemic Stroke

Inclusion Criteria:

1. Patients presenting with clinical signs of acute ischemic stroke between 4.5 and 24hours from stroke onset, or awakening and unwitnessed stroke (if the midpoint of thelast known well time is within 4.5 to 24 hours)

2. Patients aged > 18 years

3. NIHSS range from 4 to 26

4. Imaging inclusion criteria: ischemic core volume ≤ 70 mL, penumbra ≥ 10 mL andmismatch ≥ 20% (as evaluated by CT-perfusion)

5. Pre-stroke mRS score < 2

6. 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 illness that prevents 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 or >22.2 mmol/L,point-of-care glucose testing accepted)

• 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. Large (more than one-third of the territory of middle cerebral artery) region ofclear hypodensity on CT scan

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 threemonths

8. Life expectancy of less than three months