Acute Ischemic StrokePhase 3CHESTNUTNCT06994975
CHinese ischEmic Stroke Beyond 4.5 Hours With TeNecteplase Under Optimized Non-Contrast CT Selection
A Phase 3 study testing 0.25mg/kg TNK and Standard medical treatment in people with Acute Ischemic Stroke, run by Huashan Hospital at 2 sites in China.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Ischemic Stroke
- What is being tested?
- 0.25mg/kg TNK and Standard medical treatment
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 890 participants
- Where
- 2 sitesChina
- Study dates
- 3 Nov 2025to Jun 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 21Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
Huashan Hospital
Shanghai, Shanghai Municipality, 200040
Wei Huang, 52888046, hskyc@fudan.edu.cn
- Not yet recruiting
Huashan Hospital, Fudan University
Shanghai
Xin Cheng, MD, PhD, +86 021-52887145, chengxin@fudan.edu.cn
About this study
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.
Read the 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.
- Conditions
- Acute Ischemic Stroke
- Being tested
- 0.25mg/kg TNK, Standard medical treatment
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
0.25mg/kg TNKDrug
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.
Standard medical treatmentDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 0.25mg/kg TNK group | Experimental | Not described Receives: Drug: 0.25mg/kg TNK |
| Standard medical treatment | Placebo comparator | Not described Receives: Drug: Standard medical treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Participants Achieving Excellent Functional Outcome (mRS 0-1) at 90±7 Days
The primary outcome is the proportion of participants achieving excellent functional outcome (free of disability, defined as a modified Rankin Scale [mRS] score of 0-1) at 90±7 days.
Measured: at 90±7 days
Secondary outcomes (11)
Infarct Growth Volume at 3-5 Days Compared to Baseline Core
The secondary radiological efficacy outcome is infarct growth, defined as the difference in volume between the infarct volume measured by diffusion-weighted imaging (DWI) or non-contrast head CT at 3-5 days and the baseline core infarct volume.
Measured: at 3-5 days
Proportion of Participants Achieving Good Functional Outcome (mRS 0-2) at 90±7 Days
The secondary clinical efficacy outcome is the proportion of participants achieving good functional outcome (functional independence, defined as a modified Rankin Scale [mRS] score of 0-2) at 90±7 days.
Measured: at 90±7 days
Distribution of Modified Rankin Scale Scores at 90±7 Days
The secondary clinical efficacy outcome is the distribution of modified Rankin Scale (mRS) scores from 0 (no symptoms) to 6 (death) at 90±7 days post-treatment.
Measured: at 90±7 days
Proportion of Participants with Significant Neurological Improvement within 24-48 Hours
The secondary clinical efficacy outcome is the proportion of participants achieving significant neurological improvement within 24-48 hours, defined as a reduction in National Institutes of Health Stroke Scale (NIHSS) score by more than 8 points or an NIHSS score of 0-1.
Measured: within 24-48 hours
Change in NIHSS Score at 24-48 Hours
The secondary clinical efficacy outcome is the change in National Institutes of Health Stroke Scale (NIHSS) score as a continuous variable at 24-48 hours post-treatment.
Measured: at 24-48 hours
Incidence of Symptomatic Intracranial Hemorrhage within 24-48 Hours
The secondary radiological safety outcome is the incidence of symptomatic intracranial hemorrhage within 24-48 hours post-treatment, defined according to the European Cooperative Acute Stroke Study III (ECASS III) criteria.
Measured: within 24-48 hours
Incidence of Any Intracranial Hemorrhage within 24-48 Hours Post Treatment
The secondary radiological safety outcome is the incidence of any intracranial hemorrhage within 24-48 hours post-treatment, as determined by computed tomography [CT].
Measured: at 24-48 hours
Incidence of PH2 within 24-48 Hours Post Treatment
The secondary radiological safety outcome is the incidence of type 2 parenchymal hematoma (PH2) within 24-48 hours post-treatment, as determined by computed tomography [CT].
Measured: at 24-48 hours
Incidence of All-Cause Mortality within 90 Days
The secondary clinical safety outcome is the incidence of all-cause mortality within 90 days post-treatment.
Measured: within 90 days
Proportion of Participants with Poor Functional Outcome (mRS 5-6) at 90±7 Days
The secondary clinical safety outcome is the proportion of participants with poor functional outcome (severe disability or death, defined as modified Rankin Scale [mRS] score of 5-6) at 90±7 days post-treatment.
Measured: at 90±7 days
Incidence of Systemic Bleeding within 90 Days
The secondary clinical safety outcome is the incidence of systemic bleeding within 90 days post-treatment, defined according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) criteria.
Measured: within 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2025
- Study start3 Nov 2025
- Primary completionMar 2028 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Ischemic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multicenter, open-label, blinded-endpoint, randomized, controlled, phase 3 trial
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 890 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Huashan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xin Cheng, Huashan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06994975
- Sponsor's protocol ID
- KY2025-720
- Acronym
- CHESTNUT
- Status last verified
- Dec 2025
- First submitted
- 20 May 2025
- Last updated
- 30 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data collected for the study can be made available to other researchers on reasonable request and after signing appropriate data sharing agreements.
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CHinese ischEmic Stroke Beyond 4.5 Hours With TeNecteplase Under Optimized Non-Contrast CT Selection
- ClinicalTrials.gov ID
- NCT06994975
- Acronym / sponsor ID
- CHESTNUT / KY2025-720
- Conditions
- Acute Ischemic Stroke
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 890 participants (estimated)
- Lead sponsor
- Huashan HospitalUniversity, hospital or other
- Study start
- 3 Nov 2025 (actual)
- Primary completion
- Mar 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 29 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Multicenter, open-label, blinded-endpoint, randomized, controlled, phase 3 trial
| Arm | Type | Receives |
|---|---|---|
| 0.25mg/kg TNK group | Experimental | Drug: 0.25mg/kg TNK |
| Standard medical treatment | Placebo comparator | Drug: Standard medical treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 0.25mg/kg TNKPatients 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 | 0.25mg/kg TNK group |
| Standard medical treatmentPatients 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. | Drug | Standard medical treatment |
Primary outcome
Proportion of Participants Achieving Excellent Functional Outcome (mRS 0-1) at 90±7 Days
Time frame: at 90±7 days
The primary outcome is the proportion of participants achieving excellent functional outcome (free of disability, defined as a modified Rankin Scale [mRS] score of 0-1) at 90±7 days.
11 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2025.
- Individual participant dataSharing planned: Yes. Data collected for the study can be made available to other researchers on reasonable request and after signing appropriate data sharing agreements.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 0.25mg/kg TNK and Standard medical treatment in people with Acute Ischemic Stroke, run by Huashan Hospital at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xin Cheng, MD, PhD (+86 021-52887145, chengxin@fudan.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants Achieving Excellent Functional Outcome (mRS 0-1) at 90±7 Days (time frame: at 90±7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2025.