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

NCT ID: NCT06221371

Last Updated: 2025-11-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 391 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-25
• Study Completion Date: 2025-10-13

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

IVT with Tenecteplase+EVT

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.

Group Type: EXPERIMENTAL

Tenecteplase

Intervention Type: DRUG

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 EVT

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.

Group Type: ACTIVE_COMPARATOR

direct EVT

Intervention Type: DEVICE

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.

Interventions

Tenecteplase

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.

Intervention Type: DRUG

direct EVT

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.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Age≥18 years old;

2. 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';

3. 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;

4. 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];

5. Pre-morbid mRS score ≤2;

6. Baseline NIHSS 6-25 (both included);

7. Written informed consent from patients or their legally authorized representative.

Exclusion Criteria

1. Patients who decline interventional therapy or intravenous thrombolysis (IVT)；

2. Patients allergic to tenecteplase；

3. Rapidly improving symptoms at the discretion of the investigators；

4. 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；

5. Persistent blood pressure elevation (systolic > 185 mmHg or diastolic >110 mmHg), despite blood pressure lowering treatment；

6. Blood glucose < 2.8 or > 22.2 mmol/L (point of care glucose testing is acceptable)；

7. 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；

8. 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；

9. Known defect of platelet function or platelet count below 100*109/L (patients on antiplatelet agents can be included)；

10. 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；

11. Patients who would not be expected to survive more than 1 year；

12. Unable to perform CTP or MRP；

13. Large infarct on non-contrast CT brain or MRI (infarct size >1/3 MCA territory)；

14. Acute or past intracerebral hemorrhage (ICH) identified by CT or MRI, including cerebral parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid haemorrhage, and subdural / extradural hematoma；

15. Multiple arterial occlusions (bilateral MCA occlusion, MCA occlusion accompanied by basilar artery occlusion)；

16. Pregnant women, nursing mothers, or reluctant to take contraceptive measures during the trial period；

17. Unlikely to adhere to the trial protocol or follow-up；

18. 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；

19. Participation in any other interventional clinical trials within the previous 3 months.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Linyi People's Hospital

OTHER

Sponsor Role: collaborator

Beijing Tiantan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yunyun Xiong

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fengyuan Che, MD

Role: PRINCIPAL_INVESTIGATOR

Linyi People's Hospital

Yunyun Xiong, MD

Role: PRINCIPAL_INVESTIGATOR

Beijing Tiantan Hospital

Locations

The First Affiliated Hospital of USTC

Hefei, Anhui, China

First Affiliated Hospital of Wannan Medical College

Wuhu, Anhui, China

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Beijing Daxing District People's Hospital

Beijing, Beijing Municipality, China

The 2nd affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, China

Puyang Oilfield General Hospital

Puyang, Henan, China

People's Hospital of Queshan

Zhumadian, Henan, China

First People's Hospital of Chenzhou

Chenzhou, Hunan, China

Dalian Municipal Central Hospital

Dalian, Liaoning, China

First Affiliated Hospital of Xi 'an Jiaotong University

Xi'an, Shaanxi, China

Heze Municipal Hospital

Heze, Shandong, China

Jining NO.1 People's Hospital

Jining, Shandong, China

Liaocheng Third People's Hospital

Liaocheng, Shandong, China

Linyi People's Hospital

Linyi, Shandong, China

Linyi Central Hospital

Linyi, Shandong, China

Qingdao Central Hospital

Qingdao, Shandong, China

Rizhao People's Hospital

Rizhao, Shandong, China

Rizhao Traditional Chinese Medicine Hospital

Rizhao, Shandong, China

Weifang People's Hospital

Weifang, Shandong, China

Zaozhuang Municipal Hospital

Zaozhuang, Shandong, China

Zhejiang Provincial People's Hospital

Hangzhou, Zhejiang, China

Countries

China

Other Identifiers

CSA2023YJ003

Identifier Type: -

Identifier Source: org_study_id