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

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.

Inclusion criteria

• 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.

Exclusion criteria

• 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.