Overview
The purpose of this study is to evaluate the efficacy and safety of intravenous tenecteplase (0.25 mg/kg) compared with standard therapy in patients with acute ischemic stroke presenting with mild symptoms-defined as a National Institutes of Health Stroke Scale (NIHSS) score ≤5 accompanied by persistent unilateral limb weakness or speech impairment within 4.5 hours of onset.
Description
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.
Eligibility
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.
