rhTNK-tPA for Acute Ischemic Stroke Under Simplified Imaging in the Extended Time Window

rhTNK-tPA for Acute Ischemic Stroke Under Simplified Imaging in the Extended Time Window: A Multicenter, Prospective, Randomized Controlled, Open-label, Blinded-Endpoint Trial

The PEARL-SIMPLIFIED trial is a multicenter, prospective, randomized controlled, open-label, blinded-endpoint study. It aims to evaluate the efficacy and safety of intravenous tenecteplase (TNK) in patients with acute ischemic stroke (AIS) presenting in the extended 4.5-24 hour window, using a simplified imaging selection strategy based solely on non-contrast CT (NCCT).

The PEARL-SIMPLIFIED trial is a multicenter, prospective, randomized controlled, open-label, blinded-endpoint study with a target enrollment of at least 750 patients. The trial focuses on individuals with acute ischemic stroke (AIS) presenting within a 4.5 to 24-hour window who are not planned for endovascular thrombectomy (EVT). Patients meeting simplified imaging criteria based on non-contrast CT (NCCT) are randomized 1:1 to receive a single intravenous bolus of 0.25 mg/kg tenecteplase (TNK) or standard medical treatment. The primary outcome is the 90-day excellent functional outcome, defined as a modified Rankin Scale (mRS) score of 0-1. Safety outcomes include symptomatic intracranial hemorrhage (sICH) and 90-day mortality.

Inclusion Criteria:

1. Age 18 years or older.
2. Presumed acute ischemic stroke of the anterior circulation.
3. Acute ischemic stroke symptom onset between 4.5 to 24 hours prior to enrollment; including wake-up stroke and unwitnessed stroke, onset time refers to 'last-known well time'.
4. Baseline National Institutes of Health Stroke Scale (NIHSS) 6-25 (inclusive).
5. Limited early ischemic changes on non-contrast CT (NCCT).
6. Written informed consent signed by patients or their legally authorized representatives.

Exclusion Criteria:

1. Clearly demarcated hypodensity on non-contrast CT related to the current stroke, with limited anticipated clinical benefit as judged by the investigator.
2. Intracranial or subarachnoid hemorrhage identified on baseline NCCT.
3. Endovascular thrombectomy (EVT) planned at the time of randomization.
4. Pre-stroke mRS≥2.
5. Allergy to the test drug and its ingredients.
6. Severe head trauma or ischemic stroke in the last 3 months.
7. Intracranial or intraspinal surgery within 3 months before enrollment.
8. Intracranial tumor or large-size aneurysm found before enrollment.
9. Gastrointestinal or urinary system hemorrhage within the past 3 weeks.
10. Active visceral bleeding.
11. Aortic arch dissection confirmed by examination or medical history.
12. Infective endocarditis confirmed by examination or medical history.
13. Platelet count less than 100 × 109 /L.
14. Patients received heparin or low-molecular-weighted heparin treatment within 24h before enrollment.
15. Pregnant or lactating women.
16. Blood glucose <50 mg/dl (2.78mmol/L) or >400 mg/dl (22.2mmol/L) during screening.
17. Uncontrolled hypertension with persistent systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, refractory to medical management.
18. Life expectancy less than 6 months due to malignancy, severe cardiopulmonary disease, or other terminal illness.
19. Participating in other trials.
20. Other conditions deemed unsuitable for the study by the investigator, such as inability to comprehend or comply with study procedures or follow-up due to mental illness, cognitive or emotional disorder.