Acute Ischemic StrokePhase 3TRUST-MISMATCHNCT07540416
Tenecteplase for Late-Window Stroke Guided by DWI-FLAIR Mismatch
A Phase 3 study testing TNK-tPA and Aspirin in people with Acute Ischemic Stroke, run by The First Affiliated Hospital of Zhengzhou University at 1 site in China.
Trial summary
The goal of this clinical trial is to evaluate the efficacy and safety of tenecteplase administered 4.5-9 hours after stroke onset (defined as the time the patient was first found with symptoms, including wake-up stroke and unwitnessed stroke) in patients with acute ischemic stroke (AIS) guided by DWI-FLAIR mismatch… 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?
- TNK-tPA and Aspirin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 564 participants
- Where
- 1 siteChina
- Study dates
- 1 May 2026to 30 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
- Age ≥ 18 years;
- AIS with symptom onset 4.5-9 hours before enrollment, including wake-up stroke and unwitnessed stroke (onset time defined as when symptoms were first noticed);
- Imaging criteria:
- DWI-FLAIR mismatch: visible lesion on DWI with no marked visible lesion on FLAIR;
- DWI infarct core not exceeding one-third of the middle cerebral artery territory, one-half of the anterior cerebral artery territory, or one-half of the posterior cerebral artery territory;
- NIHSS score 4-25;
- First-ever stroke or previous stroke without significant disability (pre-stroke mRS ≤ 1);
- Signed informed consent from the patient or legally authorized representative.
Who cannot join
- Planned endovascular treatment;
- Contradictory to MRI examination;
- MRI image not qualified for evaluation;
- Serious neurological deficits before onset (mRS≥2);
- Obvious head injuries or strokes within 3 months;
- Subarachnoid or intracranial hemorrhage;
Show all 26Show fewer
- History of intracranial hemorrhage;
- Intracranial tumor, arteriovenous malformation or aneurysm;
- Intracranial or spinal cord surgery within 3 months;
- Active internal hemorrhage;
- platelet count of <100000/mm3;
- Aortic arch dissection;
- Heparin therapy within 24 hours;
- Oral warfarin is being taken and INR>1.6 or APTT abnormal;
- Oral anticoagulation therapy;
- Systolic pressure≥185 mmHg or diastolic pressure≥110 mmHg;
- Blood glucose < 50 mg/dl (2.7mmol/L);
- Pregnancy;
- Neurological deficit after epileptic seizures;
- Major surgery within 1 month;
- Gastrointestinal or urinary tract hemorrhage within the previous 30 days;
- Myocardial infarction within 3 months;
- Allergy to study drugs;
- Unlikely to adhere to the trial protocol or follow-up;
- Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study;
- Participation in other interventional clinical trials within the previous 3 months.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan
Zhengzhou, Henan, 450052
Bo Song, MD, +86-371-66278068, fccsongb@zzu.edu.cn
About this study
Official title: Tenecteplase Thrombolysis for Acute Ischemic Stroke in the 4.5-9-Hour Window Guided by DWI-FLAIR Mismatch: A Multicenter, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial
The goal of this clinical trial is to evaluate the efficacy and safety of tenecteplase administered 4.5-9 hours after stroke onset (defined as the time the patient was first found with symptoms, including wake-up stroke and unwitnessed stroke) in patients with acute ischemic stroke (AIS) guided by DWI-FLAIR mismatch on MRI. The main questions it aims to answer are:
- Does tenecteplase improve functional outcomes at 90 days compared with standard treatments in AIS patients administered 4.5-9 hours after stroke onset guided by DWI-FLAIR mismatch?
- The safety of tenecteplase thrombolysis for AIS patients in the 4.5-9 hours guided by DWI-FLAIR mismatch.
Read more
Researchers will compare tenecteplase to placebo to see if it is effective and safe for these patients.
Participants will be randomly assigned (1:1) immediately after randomization:
- Tenecteplase group: received tenecteplase, intravenously as a bolus administered over a period of 5 to 10 seconds at a dose of 0.25 mg per kilogram (maximum dose, 25 mg), plus aspirin placebo (300 mg).
- Control group: aspirin (300 mg) plus tenecteplase placebo. From day 2 to day 90, all patients will be conformed to the 2023 Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke.
Read the detailed description
Current clinical guidelines recommend intravenous thrombolysis (IVT) for eligible AIS patients within 4.5 hours of symptom onset. However, approximately 67 to 75% of patients present after 4.5 hours after stroke onset or with an unknown time of onset. CT perfusion (CTP) and perfusion-diffusion magnetic resonance imaging (MRI) have demonstrated that potentially viable brain tissue may persist beyond 4.5 hours after stroke onset. Recent trials, such as EXTEND, TRACE III, and the HOPE study, suggest that IVT can improve functional outcomes in AIS patients with salvageable brain tissue identified beyond 4.5 hours and up to 24 hours, using advanced perfusion imaging. Nonetheless, due to the high cost of perfusion software in developing countries, extended-window thrombolysis has not been widely implemented in many stroke centers. Therefore, it is crucial to develop alternative strategies to guide IVT in patients beyond 4.5 hours.
In recent years, the mismatch between a visible acute ischemic lesion on diffusion-weighted imaging (DWI) and the absence of a corresponding hyperintensity on fluid-attenuated inversion recovery (FLAIR) has been recognized as a predictor of symptom onset within 4.5 hours before imaging. The WAKE-UP trial demonstrated that among AIS patients with unknown time of onset (last known well >4.5 hours) and DWI-FLAIR mismatch, IVT administered within 4.5 hours after symptom recognition significantly improved functional outcomes. However, approximately 30% of AIS patients exhibit DWI-FLAIR mismatch between 4.5 and 9 hours after onset. Whether these patients can benefit from thrombolysis remains uncertain.
TRUST-MISMATCH is a multicenter, prospective, randomized, double-blind, placebo-controlled clinical. We want to evaluate the efficacy and safety of tenecteplase administered 4.5-9 hours after stroke onset (defined as the time the patient was first found with symptoms, including wake-up stroke and unwitnessed stroke) in AIS patients guided by DWI-FLAIR mismatch on MRI.
- Conditions
- Acute Ischemic Stroke
- Being tested
- TNK-tPA, Aspirin, Placebo
- Keywords
- Tenecteplase, Thrombolysis, diffusion weighted imaging, fluid attenuated inversion recovery
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TNK-tPADrug
TNK-tPA (0.25 mg/kg, to maximum of 25mg)
AspirinDrug
Asprin (300mg)
PlaceboDrug
Asprin (placebo)
PlaceboDrug
TNK-tPA (placebo)
| Study group | Role | What they receive |
|---|---|---|
| Tenecteplase group: | Experimental | Patients will receive tenecteplase, intravenously as a bolus administered over a period of 5 to 10 seconds at a dose of 0.25 mg per kilogram (maximum dose, 25 mg), plus aspirin placebo (300 mg) immediately after randomization.From day 2 to day 90, all patients will be conformed to the 2023 Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke. Receives: Drug: TNK-tPA; Drug: Placebo |
| Control group | Active comparator | Patients will receive asprin(300mg) plus intravenous TNK(placebo, 0.25mg/kg, a maximum of 25 mg) immediately after randomization. From day 2 to day 90, patients will be conformed to the 2023 Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke. Receives: Drug: Aspirin; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modified Rankin Scale (mRS)
Proportion of subjects of excellent outcome defined as mRS (0-1) at 90 ± 7 days.
Measured: 90 ± 7 days
Secondary outcomes (6)
Modified Rankin Scale (mRS)
Proportion of subjects of excellent outcome defined as mRS (0-2) at 90 ± 7 days.
Measured: 90 ± 7 days
Modified Rankin Scale (mRS)
Ordinal shift analysis of mRS at 90 days
Measured: 90 ± 7 days
National Institutes of Health Stroke Scale (NIHSS)
NIHSS change from baseline at 24 hours and 7 days.
Measured: 24 hours and 7 days
Barthel (BI)
Barthel Index score at 90 ± 7 days.
Measured: 90 ± 7 days
EuroQol 5-Dimension (EQ-5D)
Quality of life measured by EQ-5D scale at 90 ± 7 days.
Measured: 90 ± 7 days
Modified Rankin Scale (mRS)
- Proportion of subjects of excellent outcome defined as mRS (0-2) at 90 ± 7 days.
- Ordinal distribution of mRS at 90 ± 7 days
Measured: 90 ± 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2026
- Study start1 May 2026 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion30 Jun 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
- TNK group: Tenecteplase (TNK) (0.25 mg/kg, to maximum of 25mg) and asprin (placebo) Control group: Asprin (300mg) plus TNK (placebo)
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 564 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The First Affiliated Hospital of Zhengzhou University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bo Song, The First Affiliated Hospital of Zhengzhou University
- Investigators
- Bo Song, MD, Study chair, Department of Neurology, the First Affiliated Hospital of Zhengzhou University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07540416
- Sponsor's protocol ID
- MISMATCH-001
- Acronym
- TRUST-MISMATCH
- Status last verified
- Apr 2026
- First submitted
- 6 Apr 2026
- Last updated
- 20 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tenecteplase Thrombolysis for Acute Ischemic Stroke in the 4.5-9-Hour Window Guided by DWI-FLAIR Mismatch: A Multicenter, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial
- ClinicalTrials.gov ID
- NCT07540416
- Acronym / sponsor ID
- TRUST-MISMATCH / MISMATCH-001
- Conditions
- Acute Ischemic Stroke
- Keywords
- Tenecteplase, Thrombolysis, diffusion weighted imaging, fluid attenuated inversion recovery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 564 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital of Zhengzhou UniversityUniversity, hospital or other
- Study start
- 1 May 2026 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 20 Apr 2026 (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 goal of this clinical trial is to evaluate the efficacy and safety of tenecteplase administered 4.5-9 hours after stroke onset (defined as the time the patient was first found with symptoms, including wake-up stroke and unwitnessed stroke) in patients with acute ischemic stroke (AIS) guided by DWI-FLAIR mismatch on MRI. The main questions it aims to answer are:
- Does tenecteplase improve functional outcomes at 90 days compared with standard treatments in AIS patients administered 4.5-9 hours after stroke onset guided by DWI-FLAIR mismatch?
- The safety of tenecteplase thrombolysis for AIS patients in the 4.5-9 hours guided by DWI-FLAIR mismatch.
Researchers will compare tenecteplase to placebo to see if it is effective and safe for these patients.
Participants will be randomly assigned (1:1) immediately after randomization:
- Tenecteplase group: received tenecteplase, intravenously as a bolus administered over a period of 5 to 10 seconds at a dose of 0.25 mg per kilogram (maximum dose, 25 mg), plus aspirin placebo (300 mg).
- Control group: aspirin (300 mg) plus tenecteplase placebo. From day 2 to day 90, all patients will be conformed to the 2023 Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke.
Detailed description
Current clinical guidelines recommend intravenous thrombolysis (IVT) for eligible AIS patients within 4.5 hours of symptom onset. However, approximately 67 to 75% of patients present after 4.5 hours after stroke onset or with an unknown time of onset. CT perfusion (CTP) and perfusion-diffusion magnetic resonance imaging (MRI) have demonstrated that potentially viable brain tissue may persist beyond 4.5 hours after stroke onset. Recent trials, such as EXTEND, TRACE III, and the HOPE study, suggest that IVT can improve functional outcomes in AIS patients with salvageable brain tissue identified beyond 4.5 hours and up to 24 hours, using advanced perfusion imaging. Nonetheless, due to the high cost of perfusion software in developing countries, extended-window thrombolysis has not been widely implemented in many stroke centers. Therefore, it is crucial to develop alternative strategies to guide IVT in patients beyond 4.5 hours.
In recent years, the mismatch between a visible acute ischemic lesion on diffusion-weighted imaging (DWI) and the absence of a corresponding hyperintensity on fluid-attenuated inversion recovery (FLAIR) has been recognized as a predictor of symptom onset within 4.5 hours before imaging. The WAKE-UP trial demonstrated that among AIS patients with unknown time of onset (last known well >4.5 hours) and DWI-FLAIR mismatch, IVT administered within 4.5 hours after symptom recognition significantly improved functional outcomes. However, approximately 30% of AIS patients exhibit DWI-FLAIR mismatch between 4.5 and 9 hours after onset. Whether these patients can benefit from thrombolysis remains uncertain.
TRUST-MISMATCH is a multicenter, prospective, randomized, double-blind, placebo-controlled clinical. We want to evaluate the efficacy and safety of tenecteplase administered 4.5-9 hours after stroke onset (defined as the time the patient was first found with symptoms, including wake-up stroke and unwitnessed stroke) in AIS patients guided by DWI-FLAIR mismatch on MRI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- TNK group: Tenecteplase (TNK) (0.25 mg/kg, to maximum of 25mg) and asprin (placebo) Control group: Asprin (300mg) plus TNK (placebo)
| Arm | Type | Receives |
|---|---|---|
| Tenecteplase group: | Experimental | Drug: TNK-tPA, Drug: PlaceboPatients will receive tenecteplase, intravenously as a bolus administered over a period of 5 to 10 seconds at a dose of 0.25 mg per kilogram (maximum dose, 25 mg), plus aspirin placebo (300 mg) immediately after randomization.From day 2 to day 90, all patients will be conformed to the 2023 Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke. |
| Control group | Active comparator | Drug: Aspirin, Drug: PlaceboPatients will receive asprin(300mg) plus intravenous TNK(placebo, 0.25mg/kg, a maximum of 25 mg) immediately after randomization. From day 2 to day 90, patients will be conformed to the 2023 Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 18 years;
- AIS with symptom onset 4.5-9 hours before enrollment, including wake-up stroke and unwitnessed stroke (onset time defined as when symptoms were first noticed);
- Imaging criteria:
- NIHSS score 4-25;
- First-ever stroke or previous stroke without significant disability (pre-stroke mRS ≤ 1);
Key exclusion criteria (26 listed)
- Planned endovascular treatment;
- Contradictory to MRI examination;
- MRI image not qualified for evaluation;
- Serious neurological deficits before onset (mRS≥2);
- Obvious head injuries or strokes within 3 months;
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 |
|---|---|---|
| TNK-tPATNK-tPA (0.25 mg/kg, to maximum of 25mg) | Drug | Tenecteplase group: |
| AspirinAsprin (300mg) | Drug | Control group |
| PlaceboAsprin (placebo) | Drug | Tenecteplase group: |
| PlaceboTNK-tPA (placebo) | Drug | Control group |
Primary outcome
Modified Rankin Scale (mRS)
Time frame: 90 ± 7 days
Proportion of subjects of excellent outcome defined as mRS (0-1) at 90 ± 7 days.
6 secondary outcomes
Modified Rankin Scale (mRS)
Time frame: 90 ± 7 days
Modified Rankin Scale (mRS)
Time frame: 90 ± 7 days
National Institutes of Health Stroke Scale (NIHSS)
Time frame: 24 hours and 7 days
Barthel (BI)
Time frame: 90 ± 7 days
EuroQol 5-Dimension (EQ-5D)
Time frame: 90 ± 7 days
Modified Rankin Scale (mRS)
Time frame: 90 ± 7 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 20 Apr 2026.
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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.
Bo Song, MD study chair
Department of Neurology, the First Affiliated Hospital of Zhengzhou University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing TNK-tPA and Aspirin in people with Acute Ischemic Stroke, run by The First Affiliated Hospital of Zhengzhou University at 1 site 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 8 inclusion and 26 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: opening soon, as of the sponsor's last update on 20 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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 Bo Song, MD (+86-371-66278068, fccsongb@zzu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Modified Rankin Scale (mRS) (time frame: 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 20 Apr 2026.