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

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.

Detailed 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.

Interventions

• Drug 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.
• Drug 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.

Primary outcome measures

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

Secondary outcome measures (11)

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

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 2 centers

• Huashan Hospital — Shanghai
• Huashan Hospital, Fudan University — Shanghai

Identifiers

NCT: NCT06994975 · KY2025-720

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗