Teneteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-Ⅳ

This study is a multicenter, prospective, randomized, double-blind, double-dummy controlled (2 arms with 1:1 randomization) trial. Participants with acute minor ischemic stroke (baseline NIHSS≤5) within 4.5 hours of symptoms onset (symptom onset is defined by the "last seen normal" principle for wake-up stroke) will be enrolled. Eligible patients must have neurological deficits involving at least language or motor function. Participants will be randomized into 2 groups: Intervention group (rhTNK-tPA): 0.25mg/kg, the maximum dose does not exceed 25mg, plus placebo oral aspirin and clopidogrel. Aspirin 100mg and clopidogrel 300mg will be given within 6 ± 2 hours after thrombolytic therapy. Control group: Dual antiplatelet therapy with aspirin 100mg and clopidogrel 300mg, plus placebo intravenous rhTNK-tPA. Placebo oral aspirin and clopidogrel will be given within 6 ± 2 hours following the placebo thrombolytic therapy.The primary endpoint is an excellent functional outcome (a modified Rankin Scale score of 0-1) at 90-day.

Inclusion criteria

• Age ≥ 18 years;
• Onset-to-treatment time < 4.5 h; onset time defined as "last known well" time;
• Clinical diagnosis of minor ischemic stroke (NIHSS ≤ 5) with persistent unilateral limb weakness or speech symptoms, defined as a score of ≥1 on either the language item or a single limb item of the NIHSS;
• Pre-stroke mRS 0-1;
• Informed consent signed.

Exclusion criteria

• Planned or likely acute endovascular treatments before randomization;
• NIHSS 1a > 2;
• Known allergic to rhTNK-tPA;
• History of intracranial hemorrhage;
• Severe head trauma or previous stroke within 3 months；
• Intracranial or spinal surgery within 3 months;
• Gastrointestinal or urinary tract hemorrhage within 3 weeks；
• Major surgery within 2 weeks;
• Arterial puncture at a non-compressible site within 1 week；
• Intracranial tumors (excluding neuroectodermal tumors, e.g., meningiomas), large intracranial aneurysms, or arteriovenous malformations；
• Intracranial hemorrhage, including intraparenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, and subdural/epidural hematoma;
• Active visceral bleeding;
• Concomitantaortic arch dissection;
• Acute bleeding tendency, including platelet count <100×10⁹/L or other clinically significant conditions;
• Uncontrolled hypertension after active antihypertensive treatment: systolic blood pressure >180 mm Hg or diastolic >100 mm Hg;
• Blood glucose < 2.8 or > 22.2 mmol / L;
• Prior anticoagulant therapy, such as oral warfarin, with an INR >1.7 or PT >15 seconds;
• Use of heparin within 24 hours;
• Use of thrombin inhibitors or factor Xa inhibitors within 48 hours;
• Large cerebral infarction on head CT or MRI (infarction area >1/3 of the middle cerebral artery territory);
• Todd's paralysis after a seizure or other neurological/psychiatric disorders affecting cooperation;
• Severe, uncontrolled infections (e.g., acute pericarditis, infective endocarditis, or acute pancreatitis);
• Pregnant or breastfeeding women, or women unwilling to use effective contraception during the study period;
• Participation in another clinical trial within 3 months prior to screening;
• Other severe illnesses with a life expectancy of less than six months;
• Deemed unsuitable for the study or at increased risk by the investigator's judgment.