Ischemic Stroke, AcutePhase 3TNK-PLUSNCT06221371

Endovascular Treatment With or Without Preceding Intravenous Tenecteplase (TNK) in Patients With Late-window acUte Ischemic Stroke Due to Middle Cerebral Artery Occlusion

A Phase 3 study testing Tenecteplase and direct EVT in people with Ischemic Stroke, Acute and Thrombolysis, run by Beijing Tiantan Hospital at 21 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to investigate the safety and efficacy of endovascular treatment with or without preceding intravenous Tenecteplase in patients with late-window (4.5-24 hours of symptom onset) acute ischemic stroke due to middle cerebral artery (MCA) M1 or proximal M2 occlusion. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Ischemic Stroke, Acute, Thrombolysis, Endovascular Treatment
What is being tested?: Tenecteplase and direct EVT
Type of treatment: Injection or infusion, Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 391 participants
Where: 21 sitesChina
Study dates: 25 Jan 2024to 13 Oct 2025
Phase: Phase 3
Are there results?: None posted in the registry

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 old;
Acute ischemic stroke symptom onset between 4.5 to 24 hours prior to enrollment including wake-up stroke and unwitnessed stroke; onset time refers to 'last seen well time';
MCA-M1 or proximal M2 occlusions confirmed by Computer Tomography Angiography (CTA)/Magnetic Resonance Angiography (MRA) that was responsible for signs and symptoms of acute ischemic stroke;
Neuroimaging: target mismatch profile on CT perfusion (CTP) or MRI + MR perfusion imaging (MRP) (analyzed by perfusion analysis software with Class II and above medical device certificates) [ischemic core volume (defined as CBF<30% or apparent diffusion coefficient value < 620×10-6 mm2/s) <70mL, mismatch ratio≥1.8, mismatch volume≥15mL];
Pre-morbid mRS score ≤2;
Baseline NIHSS 6-25 (both included);
Written informed consent from patients or their legally authorized representative.

Who cannot join

Patients who decline interventional therapy or intravenous thrombolysis (IVT)；
Patients allergic to tenecteplase；
Rapidly improving symptoms at the discretion of the investigators；
NIHSS consciousness score 1a>2, or epileptic seizure, hemiplegia after seizures or combined with other nervous/mental illness not able to cooperate or unwilling to cooperate；
Persistent blood pressure elevation (systolic > 185 mmHg or diastolic >110 mmHg), despite blood pressure lowering treatment；
Blood glucose < 2.8 or > 22.2 mmol/L (point of care glucose testing is acceptable)；

Show all 19Show fewer

Active internal bleeding or at high risk of bleeding, e.g.: Major surgery, trauma or gastrointestinal or urinary tract haemorrhage within the previous 21 days, or arterial puncture at a non-compressible site within the previous 7 days；
Any known impairment in coagulation, e.g.: If on vitamin K antagonists, then INR >1.7 or prothrombin time >15 seconds; if use of any direct thrombin inhibitors or new oral anticoagulants (NOACs) during the last 48 hours unless reversal of effect can be achieved with idarucizumab; values in sensitivity laboratory tests exceed the upper limit of normal [including activated partial thromboplastin time (APTT), international normalized ratio (INR), platelet count, thrombin time (TT), or appropriate factor Xa activity assays, etc.]; if on heparin during the last 24 hours or with an elevated aPTT greater than the upper limit of normal；
Known defect of platelet function or platelet count below 100*109/L (patients on antiplatelet agents can be included)；
Ischemic stroke or myocardial infarction in previous 3 months, previous intracranial hemorrhage, severe traumatic brain injury, intracranial or intraspinal operation in previous 3 months, or known intracranial neoplasm (excluding neuroectodermal tumors such as meningioma), arteriovenous malformation or giant aneurysm；
Patients who would not be expected to survive more than 1 year；
Unable to perform CTP or MRP；
Large infarct on non-contrast CT brain or MRI (infarct size >1/3 MCA territory)；
Acute or past intracerebral hemorrhage (ICH) identified by CT or MRI, including cerebral parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid haemorrhage, and subdural / extradural hematoma；
Multiple arterial occlusions (bilateral MCA occlusion, MCA occlusion accompanied by basilar artery occlusion)；
Pregnant women, nursing mothers, or reluctant to take contraceptive measures during the trial period；
Unlikely to adhere to the trial protocol or follow-up；
Any condition that, in the investigator's judgment, could pose a hazard to the patient if study therapy is initiated or could impact the patient's ability to participate in the study；
Participation in any other interventional clinical trials within the previous 3 months.

Trial locations and contacts

21 sites in 1 country.

City, postcode or hospital

21 sites in 1 country

China21 sites

Beijing Tiantan Hospital, Capital Medical University
Beijing, Beijing Municipality, 100070
Beijing Daxing District People's Hospital
Beijing, Beijing Municipality
First People's Hospital of Chenzhou
Chenzhou, Hunan, 423000
Dalian Municipal Central Hospital
Dalian, Liaoning
Zhejiang Provincial People's Hospital
Hangzhou, Zhejiang
The 2nd affiliated Hospital of Harbin Medical University
Harbin, Heilongjiang
The First Affiliated Hospital of USTC
Hefei, Anhui
Heze Municipal Hospital
Heze, Shandong, 274400
Jining NO.1 People's Hospital
Jining, Shandong
Liaocheng Third People's Hospital
Liaocheng, Shandong, 252006
Linyi People's Hospital
Linyi, Shandong, 276003
Linyi Central Hospital
Linyi, Shandong
Puyang Oilfield General Hospital
Puyang, Henan
Qingdao Central Hospital
Qingdao, Shandong, 266000
Rizhao People's Hospital
Rizhao, Shandong, 276800
Rizhao Traditional Chinese Medicine Hospital
Rizhao, Shandong, 276800
Weifang People's Hospital
Weifang, Shandong
First Affiliated Hospital of Wannan Medical College
Wuhu, Anhui
First Affiliated Hospital of Xi 'an Jiaotong University
Xi'an, Shaanxi, 710061
Zaozhuang Municipal Hospital
Zaozhuang, Shandong
People's Hospital of Queshan
Zhumadian, Henan

Other trials in China

About this study

Official title: Endovascular Treatment With or Without Preceding Intravenous Tenecteplase (TNK) in Patients With Late-window acUte Ischemic Stroke Due to Middle Cerebral Artery Occlusion: a Multi-center, Prospective, Randomized, Open-label, Blinded Endpoint (PROBE), Phase 3 Trial

Read the detailed description

After being informed about the study and potential risks, patients who meet the inclusion criteria will be randomized to endovascular treatment with preceding intravenous Tenecteplase (0.25mg/kg, maximum 25mg) or without preceding intravenous Tenecteplase in a 1:1 ratio. Written informed consent will be needed.

Conditions: Ischemic Stroke, Acute, Thrombolysis, Endovascular Treatment
Being tested: Tenecteplase, direct EVT
Keywords: Endovascular Treatment, Thrombolysis, Tenecteplase, Middle cerebral artery occlusion
Medical subject headings: Ischemic Stroke, Infarction, Middle Cerebral Artery

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TenecteplaseDrug
Tenecteplase (0.25 mg/kg, maximum dose 25mg) is given as a single, intravenous bolus (injection over 5 to 10 seconds) immediately upon randomization. EVT should be performed as soon as possible after Tenecteplase administration.
direct EVTDevice
During the study period, NMPA-approved stents are permitted. EVT included thrombectomy with stent retrievers, thromboaspiration, intraarterial thrombolysis, balloon angioplasty, stenting, or a combination of these approaches at the discretion of the interventional team.

Study groups in NCT06221371
Study group	Role	What they receive
IVT with Tenecteplase+EVT	Experimental	Tenecteplase 0.25mg/kg: 1-2 vials (1.0×107 IU/16 mg per vial) Each vial of Tenecteplase is reconstituted with 3 ml sterile water for injection and adjusted to a concentration of 5.33 mg/ml. The total amount of drug will be calculated according to the subject's actual body weight and the required drug volume will be measured. The maximum dose should not exceed 25mg. Tenecteplase should be given as a single, intravenous bolus (drug administered over 5-10 seconds). Endovascular treatment (EVT) should be performed as soon as possible after Tenecteplase administration. Receives: Drug: Tenecteplase
Direct EVT	Active comparator	During the study period, NMPA-approved stents are permitted. EVT included thrombectomy with stent retrievers, thromboaspiration, intraarterial thrombolysis, balloon angioplasty, stenting, or a combination of these approaches at the discretion of the interventional team. Receives: Device: direct EVT

What is being measured

The primary outcome is the main question the study is designed to answer.

The modified Rankin Scale (mRS) score 0 to 2 at 90 days
The proportion of the modified Rankin Scale (mRS) score 0 to 2 at 90 days. Scores on the mRS range from 0 to 6, with higher scores indicating greater disability.
Measured: 90 days

Secondary outcomes (9)

Ordinal shift analysis of mRS at 90 days (not combined mRS 5 and 6)
Ordinal shift analysis of mRS at 90 days (not combined mRS 5 and 6). Scores on the mRS range from 0 to 6, with higher scores indicating greater disability.
Measured: 90 days
mRS 0-1 at 90 days
The proportion of mRS score 0 - 1 at 90 days. Scores on the mRS range from 0 to 6, with higher scores indicating greater disability.
Measured: 90 days
mRS 0-3 at 90 days
The proportion of mRS 0 - 3 at 90 days. Scores on the mRS range from 0 to 6, with higher scores indicating greater disability.
Measured: 90 days
mRS 5-6 at 90 days
The proportion of mRS 5 - 6 at 90 days. Scores on the mRS range from 0 to 6, with higher scores indicating greater disability.
Measured: 90 days
NIHSS≤1 or a decrease of 8 points or more from baseline at 72h after randomization
NIHSS≤1 or a decrease of 8 points or more from baseline at 72h after randomization. Scores on the National Institutes of Health Stroke Scale (NIHSS) range from 0 to 42, with higher scores indicating a greater deficit.
Measured: 72 hours
Change in stroke severity (NIHSS score) at 7 days after randomization from baseline
Change in stroke severity (NIHSS score) at 7 days after randomization from baseline. Scores on the NIHSS range from 0 to 42, with higher scores indicating a greater deficit.
Measured: 7 days
Successful reperfusion prior to endovascular treatment by DSA (eTICI 2b50-3)
Successful reperfusion prior to endovascular treatment by DSA (expanded Treatment in Cerebral Infarction[eTICI] 2b50-3)
Measured: 0 hours (at treatment time)
Complete recanalization according to CTA or MRA performed 24 hours after randomization
Complete recanalization according to CTA or MRA performed 24 hours after randomization (arterial occlusive lesion score [AoL]; scale range, 0 [no recanalization] to 3 [complete recanalization]).
Measured: 24 hours
Good reperfusion at 24h after randomization
Good reperfusion at 24h after randomization (Tmax>6s improved by 90% compared with before)
Measured: 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Jan 202413 Oct 2025

First posted24 Jan 2024
Study start25 Jan 2024
Primary completion13 Oct 2025
Study completion13 Oct 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Ischemic Stroke, AcuteStudies of the same condition, open and under way.
More trials run by Beijing Tiantan HospitalThe sponsor's other registered studies.
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: A multi-center, prospective, randomized, open-label, blinded endpoint (PROBE) clinical trial
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 391 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06221371
Sponsor's protocol ID: CSA2023YJ003
Acronym: TNK-PLUS
Status last verified: Nov 2025
First submitted: 15 Jan 2024
Last updated: 26 Nov 2025
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

Publications

Xiong Y, Che F, Wang H, Hao M, Nguyen TN, Fisher M, Jin A, Cao Z, Wang Z, Yao X, Feng G, Xu Y, Guo S, Qin H, Huang X, Xu J, Chen Z, Yuan J, Li W, Hu W, Feng X, Zong L, Ye W, Duan C, Wang L, Wu S, Campbell BCV, Wang Y; TNK-PLUS Investigators. Intravenous Tenecteplase Prior to Endovascular Treatment for Ischemic Stroke at 4.5 to 24 Hours: The TNK-PLUS Randomized Clinical Trial. JAMA. 2026 Jun 2;335(21):1849-1858. doi: 10.1001/jama.2026.4292.
PubMed 42099212

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 26 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Endovascular Treatment With or Without Preceding Intravenous Tenecteplase (TNK) in Patients With Late-window acUte Ischemic Stroke Due to Middle Cerebral Artery Occlusion: a Multi-center, Prospective, Randomized, Open-label, Blinded Endpoint (PROBE), Phase 3 Trial
ClinicalTrials.gov ID: NCT06221371
Acronym / sponsor ID: TNK-PLUS / CSA2023YJ003
Conditions: Ischemic Stroke, Acute, Thrombolysis, Endovascular Treatment
Keywords: Endovascular Treatment, Thrombolysis, Tenecteplase, Middle cerebral artery occlusion
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 391 participants (actual)
Lead sponsor: Beijing Tiantan HospitalUniversity, hospital or other
Collaborators: Linyi People's Hospital
Study start: 25 Jan 2024 (actual)
Primary completion: 13 Oct 2025 (actual)
Study completion: 13 Oct 2025 (actual)
First posted: 24 Jan 2024 (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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (outcomes assessor)
Number of arms: 2
Model description: A multi-center, prospective, randomized, open-label, blinded endpoint (PROBE) clinical trial

Arm	Type	Receives
IVT with Tenecteplase+EVT	Experimental	Drug: TenecteplaseTenecteplase 0.25mg/kg: 1-2 vials (1.0×107 IU/16 mg per vial) Each vial of Tenecteplase is reconstituted with 3 ml sterile water for injection and adjusted to a concentration of 5.33 mg/ml. The total amount of drug will be calculated according to the subject's actual body weight and the required drug volume will be measured. The maximum dose should not exceed 25mg. Tenecteplase should be given as a single, intravenous bolus (drug administered over 5-10 seconds). Endovascular treatment (EVT) should be performed as soon as possible after Tenecteplase administration.
Direct EVT	Active comparator	Device: direct EVTDuring the study period, NMPA-approved stents are permitted. EVT included thrombectomy with stent retrievers, thromboaspiration, intraarterial thrombolysis, balloon angioplasty, stenting, or a combination of these approaches at the discretion of the interventional team.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Age≥18 years old;
Acute ischemic stroke symptom onset between 4.5 to 24 hours prior to enrollment including wake-up stroke and unwitnessed stroke; onset time refers to 'last seen well time';
MCA-M1 or proximal M2 occlusions confirmed by Computer Tomography Angiography (CTA)/Magnetic Resonance Angiography (MRA) that was responsible for signs and symptoms of acute ischemic stroke;
Neuroimaging: target mismatch profile on CT perfusion (CTP) or MRI + MR perfusion imaging (MRP) (analyzed by perfusion analysis software with Class II and above medical device certificates) [ischemic core volume (defined as CBF<30% or apparent diffusion coefficient value < 620×10-6 mm2/s) <70mL, mismatch ratio≥1.8, mismatch volume≥15mL];
Pre-morbid mRS score ≤2;

Key exclusion criteria (19 listed)

Patients who decline interventional therapy or intravenous thrombolysis (IVT)；
Patients allergic to tenecteplase；
Rapidly improving symptoms at the discretion of the investigators；
NIHSS consciousness score 1a>2, or epileptic seizure, hemiplegia after seizures or combined with other nervous/mental illness not able to cooperate or unwilling to cooperate；
Persistent blood pressure elevation (systolic > 185 mmHg or diastolic >110 mmHg), despite blood pressure lowering treatment；

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
TenecteplaseTenecteplase (0.25 mg/kg, maximum dose 25mg) is given as a single, intravenous bolus (injection over 5 to 10 seconds) immediately upon randomization. EVT should be performed as soon as possible after Tenecteplase administration.	Drug	IVT with Tenecteplase+EVT
direct EVTDuring the study period, NMPA-approved stents are permitted. EVT included thrombectomy with stent retrievers, thromboaspiration, intraarterial thrombolysis, balloon angioplasty, stenting, or a combination of these approaches at the discretion of the interventional team.	Device	Direct EVT

Primary outcome

The modified Rankin Scale (mRS) score 0 to 2 at 90 days
Time frame: 90 days
The proportion of the modified Rankin Scale (mRS) score 0 to 2 at 90 days. Scores on the mRS range from 0 to 6, with higher scores indicating greater disability.

9 secondary outcomes

Ordinal shift analysis of mRS at 90 days (not combined mRS 5 and 6)
Time frame: 90 days
mRS 0-1 at 90 days
Time frame: 90 days
mRS 0-3 at 90 days
Time frame: 90 days
mRS 5-6 at 90 days
Time frame: 90 days
NIHSS≤1 or a decrease of 8 points or more from baseline at 72h after randomization
Time frame: 72 hours
Change in stroke severity (NIHSS score) at 7 days after randomization from baseline
Time frame: 7 days
Successful reperfusion prior to endovascular treatment by DSA (eTICI 2b50-3)
Time frame: 0 hours (at treatment time)
Complete recanalization according to CTA or MRA performed 24 hours after randomization
Time frame: 24 hours
Good reperfusion at 24h after randomization
Time frame: 24 hours

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2025.
Derived from this study: PubMed 42099212Xiong Y, Che F, Wang H, Hao M, Nguyen TN, Fisher M, Jin A, Cao Z, Wang Z, Yao X, Feng G, Xu Y, Guo S, Qin H, Huang X, Xu J, Chen Z, Yuan J, Li W, Hu W, Feng X, Zong L, Ye W, Duan C, Wang L, Wu S, Campbell BCV, Wang Y; TNK-PLUS Investigators. Intravenous Tenecteplase Prior to Endovascular Treatment for Ischemic Stroke at 4.5 to 24 Hours: The TNK-PLUS Randomized Clinical Trial. JAMA. 2026 Jun 2;335(21):1849-1858. doi: 10.1001/jama.2026.4292.

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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. This study is not recruiting at the moment.

Fengyuan Che, MD principal investigator

Linyi People's Hospital

Yunyun Xiong, MD principal investigator

Beijing Tiantan Hospital

21 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 Tenecteplase and direct EVT in people with Ischemic Stroke, Acute and Thrombolysis, run by Beijing Tiantan Hospital at 21 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 19 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: finished, as of the sponsor's last update on 26 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 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. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The modified Rankin Scale (mRS) score 0 to 2 at 90 days (time frame: 90 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06221371, which also lists 1 linked publication.

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 26 Nov 2025.