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

Phase 3

Recruiting

• Conditions: Thrombolysis; Ischemic Stroke, Acute; Endovascular Treatment
• Interventions: Device: direct EVT; Drug: rhTNK-tPA

• Registration Number: NCT06221371
• Lead Sponsor: Beijing Tiantan Hospital

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 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 rhTNK-tPA (0.25mg/kg, maximum 25mg) or without preceding intravenous rhTNK-tPA in a 1:1 ratio. Written informed consent will be needed.

Study Timeline

• Study Start: 2023-12-16
• Study First Submitted: 2024-01-15
• Study First Submitted QC: 2024-01-15
• Study First Posted: 2024-01-24
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-16
• Last Update Posted: 2024-05-17
• Primary Completion: 2024-12
• Study Completion: 2025-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 390

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Direct EVT	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.
IVT with rhTNK-tPA+EVT	rhTNK-tPA	rhTNK-tPA 0.25mg/kg: 1-2 vials (1.0×107 IU/16 mg per vial) Each vial of rhTNK-tPA 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. rhTNK-tPA 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 rhTNK-tPA administration.

Primary Outcome Measures

Name	Time	Method
The modified Rankin Scale score (mRS) 0 to 2 at 90 days	90 days	The proportion of the modified Rankin Scale score (mRS) 0 to 2 at 90 days

Secondary Outcome Measures

Name	Time	Method
mRS 0-1 at 90 days	90 days	The proportion of mRS 0 - 1 at 90 days
NIHSS≤1 or a decrease of 8 points or more from baseline at 72h after randomization	72 hours	NIHSS≤1 or a decrease of 8 points or more from baseline at 72h after randomization
mRS at 90 days (shift analysis)	90 days	Ordinal distribution of mRS at 90 days
mRS 0-3 at 90 days	90 days	The proportion of mRS 0 - 3 at 90 days
mRS 5-6 at 90 days	90 days	The proportion of mRS 5 - 6 at 90 days
Change of stroke severity at 7 days after randomization from baseline	7 days	Change of stroke severity (NIHSS score) at 7 days after randomization from baseline
Successful recanalization prior to EVT by DSA	0 hours (at treatment time)	Successful recanalization prior to EVT by DSA (defined as eTICI score of 2b50-3)
Complete recanalization according to CTA or MRA performed 24 hours after randomization	24 hours	Complete recanalization according to CTA or MRA performed 24 hours after randomization (AoL recanalization score)
Good reperfusion at 24h after randomization	24 hours	Good reperfusion at 24h after randomization (Tmax\>6s improved by 90% compared with before)

Trial Locations

Locations (10)

First Affiliated Hospital of Xi 'an Jiaotong University; 🇨🇳 Xi'an, Shaanxi, China

Eastern Theater General Hospital; 🇨🇳 Nanjing, Jiangsu, China

Beijing Tiantan Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

Heze Municipal Hospital; 🇨🇳 Heze, Shandong, China

Liaocheng Third People's Hospital; 🇨🇳 Liaocheng, Shandong, China

Linyi People's 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

Linfen Central Hospital; 🇨🇳 Linfen, Shanxi, China