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

Capital Medical University

Status and phase: Enrolling; Phase 3

Conditions: Endovascular Treatment; Ischemic Stroke, Acute; Thrombolysis

Treatments: Drug: rhTNK-tPA; Device: direct EVT

Study type: Interventional

Funder types: Other

Identifiers

NCT06221371

CSA2023YJ003

Details and patient eligibility

About

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.

Full 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.

Enrollment: 390 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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390 participants in 2 patient groups

IVT with rhTNK-tPA+EVT

Experimental group

Description:

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.

Treatment:

Drug: rhTNK-tPA

Direct EVT

Active Comparator group

Description:

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.

Treatment:

Device: direct EVT