Unknown Time of Onset Stroke RePerfusIon Without Advanced Imaging

Intravenous Tenecteplase for Acute Ischemic Stroke With Unknown Time of Onset Under Non-Contrast CT Selection: A Multicenter, Prospective, Randomized, Open-label, Blinded Endpoint Trial

The benefit of intravenous tenecteplase for acute ischemic stroke with unknown time of onset, e.g. wake-up stroke, remains uncertain. This randomized study aims to assess the efficacy and safety of intravenous tenecteplase following non-contrast CT screening for acute ischemic stroke with unknown time of onset.

UTOPIA is an investigator-initiated, multicenter, prospective, randomized, open-label, blinded endpoint (PROBE) trial that aims to assess the efficacy and safety of intravenous tenecteplase for acute ischemic stroke with unknown time of onset, selected by non-contrast CT. The primary outcome is excellent outcome, as defined by a score of 0 or 1 on modified Rankin Scale (mRS) at 90 days.

Participants randomized to the intervention group will receive intravenous tenecteplase at 0.25 mg/kg with a maximum dose of 25 mg and standard medical treatment, and those randomized to the control group will receive standard medical treatment only, without intravenous thrombolysis.

Inclusion Criteria:

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

Exclusion Criteria:

1. Intracranial hemorrhage confirmed by skull CT, or history of intracranial hemorrhage.
2. Rapid neurological improvement with NIHSS <6 at randomization.
3. Allergy to tenecteplase.
4. 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.
5. Hypodensity on non-contrast CT >1/3 middle cerebral artery territory.
6. Severe traumatic brain injury or other major trauma in the past 3 months.
7. Intracranial neoplasm, arteriovenous malformation, or aneurysm (≥10mm).
8. Intracranial surgery, intraspinal surgery, or other major surgery in the past 3 months.
9. Gastrointestinal or urinary tract hemorrhage in the past 3 weeks.
10. Active internal bleeding.
11. Aortic dissection.
12. Infective endocarditis.
13. Platelet count <100×10^9/L.
14. Women who are pregnant or breastfeeding.
15. Blood glucose <50 or >400 mg/dL (<2.78 or >22.2 mmol/L).
16. Systolic blood presure >185 mmHg or diastolic blood presure >110 mmHg refractory to treatment.
17. Life expectancy <3 months.
18. Participating in other trials.
19. 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).