CHinese ischEmic Stroke Beyond 4.5 Hours With TeNecteplase Under Optimized Non-Contrast CT Selection

Обзор

The CHESTNUT trial is a multicenter, open-label, blinded-endpoint, randomized, controlled, phase 3 trial. The primary objective of this study is to explore the efficacy and safety of the dose of 0.25 mg/kg tenecteplase (TNK) in Chinese acute ischemic stroke (AIS) patients without substantial infarction on non-contrast computed tomography (NCCT) in an extended time window.

Подробное описание

CHinese ischEmic Stroke beyond 4.5 Hours with TeNecteplase Under optimized Non-Contrast CT selection (CHESTNUT) is a multicenter, open-label, blinded-endpoint, randomized, controlled, phase 3 study. Patients with acute strokes who are unable to undergo endovascular thrombectomy and exhibit no substantial infarction lesion on non-contrast computed tomography (less than 50 mL according to the automated NCCT post-processing model and no visible hypodensity in more than 1/3 of the middle cerebral artery \[MCA\] territory) are randomly assigned in a 1:1 ratio to receive either 0.25 mg/kg TNK or standard medical treatment. The efficacy and safety of 0.25 mg/kg TNK are assessed through clinical prognosis at 90 days.

Вмешательства

• Препарат 0.25mg/kg TNK
  Patients in the tenecteplase group were administered a 0.25mg/kg dose as a bolus over 5-10 seconds, followed by a 2 mL saline flush.
• Препарат Standard medical treatment
  Patients in the standard medical treatment group will receive the standard treatment selected by local doctors, including antithrombotic agents, lipid-lowering agents, antihypertensive drugs, and hypoglycemic agents. Patients would be ineligible if bridging endovascular treatment is planned at the time of randomization.

Первичные конечные точки

• Proportion of Participants Achieving Excellent Functional Outcome (mRS 0-1) at 90±7 Days [Срок оценки: at 90±7 days]

Вторичные конечные точки (11)

• Infarct Growth Volume at 3-5 Days Compared to Baseline Core [Срок оценки: at 3-5 days]
• Proportion of Participants Achieving Good Functional Outcome (mRS 0-2) at 90±7 Days [Срок оценки: at 90±7 days]
• Distribution of Modified Rankin Scale Scores at 90±7 Days [Срок оценки: at 90±7 days]
• Proportion of Participants with Significant Neurological Improvement within 24-48 Hours [Срок оценки: within 24-48 hours]
• Change in NIHSS Score at 24-48 Hours [Срок оценки: at 24-48 hours]
• Incidence of Symptomatic Intracranial Hemorrhage within 24-48 Hours [Срок оценки: within 24-48 hours]
• Incidence of Any Intracranial Hemorrhage within 24-48 Hours Post Treatment [Срок оценки: at 24-48 hours]
• Incidence of PH2 within 24-48 Hours Post Treatment [Срок оценки: at 24-48 hours]
• Incidence of All-Cause Mortality within 90 Days [Срок оценки: within 90 days]
• Proportion of Participants with Poor Functional Outcome (mRS 5-6) at 90±7 Days [Срок оценки: at 90±7 days]
• Incidence of Systemic Bleeding within 90 Days [Срок оценки: within 90 days]

Критерии участия

Критерии включения

• Suspected acute ischemic stroke of anterior cerebral circulation.
• Last known well time >4.5 hours.
• Age ≥18 years old.
• Baseline NIHSS (National Institutes of Health Stroke Scale) score >5.
• Premorbid modified Rankin Scale (mRS) ≤1.
• Imaging criteria: Automated infarct segmentation by NCCT post-processing model indicates infarct core volume <50 mL with no visible hypodensity in >1/3 of the MCA territory.
• Informed consent signed by the patient or the patient's legally authorized representative.

Критерии исключения

• Obvious hypodensity on NCCT deemed related with the current stroke event, with no expected benefit from thrombolysis as assessed by the investigators
• Endovascular thrombectomy (EVT) planned at the time of randomization
• Allergy to the test drug and its ingredients
• Rapidly improving symptoms at the discretion of the investigator
• Any sign of an acute intracranial hemorrhage or subarachnoid hemorrhage identified on baseline NCCT
• History of any intracranial hemorrhage
• History of ischemic stroke or major head trauma within the last 3 months
• History of intracranial/intraspinal surgery during the last 3 months
• Gastrointestinal malignancy or gastrointestinal bleeding within 21 days
• Known bleeding diatheses; platelets count < 100000/mm3, international normalized ratio > 1.7, prothrombin time > 15 s, or activated partial thromboplastin clotting time > 40 s
• Treatment with a full dosage of low-molecular weighted heparin in the last 24 hours
• Treatment with direct thrombin inhibitors or direct factor Xa inhibitors within the previous 48 hours unless the laboratory test of coagulation function is normal
• Initial systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥100 mmHg
• Initial glucose levels <2.8 or 22.22 mmol/L
• Known or suspected aortic arch dissection

In addition to:

• Clinical presentation or imaging profile consistent with Moyamoya disease/syndrome.
• Pregnancy or breastfeeding.
• Recent participation in another investigational drug or device study or registry in the past 30 days before enrollment.
• Any terminal illness such that the patient would not be expected to survive more than three months.
• Other conditions in which investigators believe that participating in this study may be harmful to the patient.

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

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Huashan Hospital — Шанхай
• Huashan Hospital, Fudan University — Шанхай

Идентификаторы

NCT: NCT06994975 · KY2025-720

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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