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

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.

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:

1. Suspected acute ischemic stroke of anterior cerebral circulation.
2. Last known well time >4.5 hours.
3. Age ≥18 years old.
4. Baseline NIHSS (National Institutes of Health Stroke Scale) score >5.
5. Premorbid modified Rankin Scale (mRS) ≤1.
6. 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.
7. Informed consent signed by the patient or the patient's legally authorized representative.

Exclusion Criteria:

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

In addition to:

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