Endovascular treatment for late-window acute ischemic stroke

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, Open-label, Blinded Endpoint (PROBE), Phase 3, Randomized Controlled Trial

This study is testing if giving a medication called Tenecteplase before a specific procedure can help people who have had a stroke due to a blocked artery feel better when treated later than usual.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 390 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Beijing Tiantan Hospital (Academic / other)
• Drugs / interventions: idarucizumab
• Locations: 10 sites (Beijing, Beijing and 9 other locations)
• Trial ID: NCT06221371 on ClinicalTrials.gov

What this trial studies

This study investigates the safety and efficacy of endovascular treatment for patients experiencing late-window acute ischemic stroke due to middle cerebral artery occlusion. Participants will be randomized to receive either intravenous Tenecteplase before the endovascular treatment or proceed directly to the treatment without it. The study aims to determine if the addition of Tenecteplase improves outcomes for patients treated within 4.5 to 24 hours of symptom onset. Patients will be monitored for safety and effectiveness based on specific neuroimaging criteria.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older who have experienced an acute ischemic stroke with symptom onset between 4.5 to 24 hours prior to enrollment.

Not a fit: Patients who decline interventional therapy or have contraindications to Tenecteplase will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could enhance recovery outcomes for patients suffering from acute ischemic strokes.

How similar studies have performed: Other studies have explored similar endovascular approaches, but the specific combination of treatments in this study is novel.

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 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 + perfusion weighted imaging (PWI) (analyzed by perfusion analysis software with Class II and above medical device certificates) \[ischemic core volume (defined as CBF\<30%) \<70mL, mismatch ratio≥1.8, mismatch volume≥15mL\].
5. Pre-stroke 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 Recombinant Human TNK Tissue-type Plasminogen Activator for Injection (rhTNK-tPA).
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 (on random glucose testing is acceptable).
7. Active internal bleeding or at high risk of bleeding, e.g.: Major surgery, trauma or gastrointestinal or urinary tract hemorrhage 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 (neuroectodermal tumor excluded like 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 PWI.
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 hemorrhage, 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.

Where this trial is running

Beijing, Beijing and 9 other locations

• Beijing Tiantan Hospital, Capital Medical University — Beijing, Beijing, China (Active_not_recruiting)
• Eastern Theater General Hospital — Nanjing, Jiangsu, China (Active_not_recruiting)
• First Affiliated Hospital of Xi 'an Jiaotong University — Xi'an, Shaanxi, China (Active_not_recruiting)
• Heze Municipal Hospital — Heze, Shandong, China (Active_not_recruiting)
• Liaocheng Third People's Hospital — Liaocheng, Shandong, China (Active_not_recruiting)
• Linyi People's Hospital — Linyi, Shandong, China (Recruiting)
• Qingdao Central Hospital — Qingdao, Shandong, China (Active_not_recruiting)
• Rizhao People's Hospital — Rizhao, Shandong, China (Active_not_recruiting)
• Rizhao Traditional Chinese Medicine Hospital — Rizhao, Shandong, China (Active_not_recruiting)
• Linfen Central Hospital — Linfen, Shanxi, China (Active_not_recruiting)

Study contacts

• Principal investigator: Fengyuan Che, MD — Linyi People's Hospital
• Study coordinator: Yunyun Xiong, MD

Conditions Ischemic Stroke, Acute; Thrombolysis; Endovascular Treatment; Tenecteplase; Middle cerebral artery occlusion