Teneteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-Ⅳ

Официальное название

TNK-tPA Treatment for Acute Minor Ischemic Stroke：A Randomized, Double-blind, Double-dummy Controlled Trial

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат rhTNK-tPA
  rhTNK-tPA 0.25mg/kg, the maximum dose does not exceed 25mg: 1 vial is dissolved in 3ml of sterile water for injection to prepare a medicinal solution with a concentration of 5.33mg/ml. Calculate the total amount of the drug according to the weight of participant, and the maximum dose shall not exceed 25 mg. It is administered as a single bolus intravenous injection, and the injection is completed within 5-10 seconds. Additionally, placebo oral aspirin and clopidogrel are given. Aspirin 100 mg an
• Препарат Control group (Aspirin combined with clopidogrel)
  Dual antiplatelets with aspirin 100mg and clopidogrel 300mg, plus placebo intravenous rhTNK-tPA. Placebo oral aspirin and clopidogrel are administered within 6 ± 2 hours following intravenous placebo.

Первичные конечные точки

• Excellent functional outcome (Modified Rankin Scale score, mRS 0-1) at 90-day (± 7 days). [Срок оценки: at 90-day (± 7 days)]

Вторичные конечные точки (12)

• Good functional outcome (mRS 0-2) at 90-day (± 7 days) [Срок оценки: at 90-day (± 7 days)]
• mRS score at 90-day (± 7 days) [Срок оценки: at 90-day (± 7 days)]
• COSMOS Scale 0-1 at 90-day (±7days) [Срок оценки: 90-day± 7days]
• COSMOS scale at 90-day (±7 days) [Срок оценки: 90-day± 7days]
• NIHSS 0-1 at 24-hour, 7-day or before discharge (analyze which occurs first) or/ neurological improvement (NIHSS decreased≥4 from baseline) [Срок оценки: at 24-hour, 7-day or before discharge (analyze which occurs first)]
• Neurological deterioration at 90 days [Срок оценки: 90-day (±7 days)]
• New clinical vascular events (ischemic stroke/ hemorrhagic stroke/ myocardial infarction/vascular death) at 90-day (± 7 days), with each vascular event being independently evaluated. [Срок оценки: at 90-day (± 7 days)]
• European quality of life visual analogue scale at 90 days [Срок оценки: at 90-day (± 7 days)]
• Symptomatic intracranial hemorrhage according to the ECASSIII criteria within 36-hour. [Срок оценки: within 36-hour]
• Symptomatic intracranial hemorrhage according to the ECASSIII criteria within 7 days or before discharge. [Срок оценки: within 7 days or before discharge]
• Symptomatic intracranial hemorrhage according to the ECASSIII criteria within 90-day (± 7 days) [Срок оценки: within 90-day (± 7 days)]
• PH2 type intracranial hemorrhage according to the Heidelberg criteria within 90-day (± 7 days) [Срок оценки: within 90-day (± 7 days)]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Beijing Tiantan Hospital — Пекин

Идентификаторы

NCT: NCT06414499 · NCRC-2024-03

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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