Overview
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.
Description
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.
Eligibility
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.