Tenecteplase for ischemic stroke given after 4.5 hours when CT shows a small infarct

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

This trial will try whether a single 0.25 mg/kg dose of tenecteplase helps adults with anterior-circulation ischemic stroke who present more than 4.5 hours after last known well and whose non-contrast CT shows limited infarction.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 890 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Huashan Hospital (Academic / other)
• Locations: 2 sites (Shanghai, Shanghai Municipality and 1 other locations)
• Trial ID: NCT06994975 on ClinicalTrials.gov

What this trial studies

CHESTNUT is a multicenter, open-label, blinded-endpoint, randomized phase 3 trial comparing one 0.25 mg/kg intravenous dose of tenecteplase to standard medical treatment in Chinese patients with acute anterior-circulation ischemic stroke who are beyond 4.5 hours and are not candidates for endovascular thrombectomy. Eligible patients are selected using automated non-contrast CT post-processing to ensure infarct core volume is less than 50 mL and there is no visible hypodensity in more than one-third of the MCA territory. Participants are randomized 1:1 and followed with blinded assessment of clinical outcomes, with primary efficacy and safety measured at 90 days. The protocol emphasizes standardized NCCT selection and centralized outcome adjudication to minimize bias.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) with anterior-circulation acute ischemic stroke, last known well >4.5 hours, baseline NIHSS >5, premorbid mRS ≤1, and NCCT showing infarct core <50 mL with no hypodensity in >1/3 of the MCA territory.

Not a fit: Patients with large established infarcts on NCCT, any acute intracranial hemorrhage, a plan for thrombectomy at randomization, rapidly improving symptoms, or an allergy to tenecteplase are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, this approach could safely extend intravenous thrombolysis to more patients who arrive late and improve their chances of functional recovery.

How similar studies have performed: Prior trials of tenecteplase within standard treatment windows and imaging-selected thrombolysis (including perfusion-based selection) have shown promise, but NCCT-guided thrombolysis beyond 4.5 hours is less well established.

Eligibility criteria

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.

Where this trial is running

Shanghai, Shanghai Municipality and 1 other locations

• Huashan Hospital — Shanghai, Shanghai Municipality, China (Recruiting)
• Huashan Hospital, Fudan University — Shanghai, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Xin Cheng, MD, PhD

Conditions Acute Ischemic Stroke