Unknown Time of Onset Stroke RePerfusIon Without Advanced Imaging

Prior treatment

• Intracranial surgery, intraspinal surgery, or other major surgery in the past 3 months.

Other illness

• Intracranial hemorrhage confirmed by skull CT, or history of intracranial hemorrhage.
• Allergy to tenecteplase.
• Gastrointestinal or urinary tract hemorrhage in the past 3 weeks.
• Active internal bleeding.
• Any condition that, in the judgment of the investigator, makes the patient unsuitable for this study or where this study may impose a significant risk to the patient (e.g., inability to understand and/or comply with study procedures and/or follow-up due to psychiatric disorders, cognitive or emotional impairment).

Lab values

• Use of vitamin K antagonist with INR \>1.7, use of heparin or low molecular heparin in the past 24 hours, or use of direct oral anticoagulants in the past 48 hours.
• Platelet count \<100×10\^9/L.
• Blood glucose \<50 or \>400 mg/dL (\<2.78 or \>22.2 mmol/L).

Other

• Planned endovascular treatment.
• Rapid neurological improvement with NIHSS \<6 at randomization.
• Hypodensity on non-contrast CT \>1/3 middle cerebral artery territory.
• Severe traumatic brain injury or other major trauma in the past 3 months.
• Intracranial neoplasm, arteriovenous malformation, or aneurysm (≥10mm).
• Aortic dissection.
• Infective endocarditis.
• Women who are pregnant or breastfeeding.
• Systolic blood presure \>185 mmHg or diastolic blood presure \>110 mmHg refractory to treatment.
• Life expectancy \<3 months.
• Participating in other trials.

• Age ≥ 18 years old.
• Clinical diagnosis of acute ischemic stroke.
• Unknown time of stroke onset (e.g., stroke symptom recognized on awakening) but last-known normal time \>4.5 hours.
• Time from stroke symptom recognition (e.g., awakening) to randomization within 3 hours.
• National Institutes of Health Stroke Scale (NIHSS) score of 6-25 (both inclusive).
• Pre-stroke modified Rankin Scale (mRS) score of 0-1.
• Written informed consent from patients or their legally authorized representatives.