Clinical trial NCT06221371: Endovascular Treatment With or Without Preceding Intravenous Tenecteplase (TNK) in Patients With Late-window acUte Ischemic Stroke Due to Middle Cerebral Artery Occlusion
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, Open-label, Blinded Endpoint (PROBE), Phase 3, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Ischemic Stroke, Acute
Thrombolysis
Endovascular Treatment
Keywords: Endovascular Treatment
Thrombolysis
Tenecteplase
Middle cerebral artery occlusion
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
Collaborators: name: Linyi People's Hospital
First posted: 2024-01-24
Enrollment: 390
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A multi-center, prospective, open-label, blinded endpoint (PROBE), randomized, controlled clinical trial
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The modified Rankin Scale score (mRS) 0 to 2 at 90 days
timeFrame: 90 days
Secondary outcomes:
measure: mRS at 90 days (shift analysis)
timeFrame: 90 days
measure: mRS 0-1 at 90 days
timeFrame: 90 days
measure: mRS 0-3 at 90 days
timeFrame: 90 days
measure: mRS 5-6 at 90 days
timeFrame: 90 days
measure: NIHSS≤1 or a decrease of 8 points or more from baseline at 72h after randomization
timeFrame: 72 hours
measure: Change of stroke severity at 7 days after randomization from baseline
timeFrame: 7 days
measure: Successful recanalization prior to EVT by DSA
timeFrame: 0 hours (at treatment time)
measure: Complete recanalization according to CTA or MRA performed 24 hours after randomization
timeFrame: 24 hours
measure: Good reperfusion at 24h after randomization
timeFrame: 24 hours
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
state: Beijing
city: Nanjing
country: China
facility: Eastern Theater General Hospital
state: Jiangsu
city: Xi'an
country: China
facility: First Affiliated Hospital of Xi 'an Jiaotong University
state: Shaanxi
city: Heze
country: China
facility: Heze Municipal Hospital
state: Shandong
city: Liaocheng
country: China
facility: Liaocheng Third People's Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi People's Hospital
state: Shandong
city: Qingdao
country: China
facility: Qingdao Central Hospital
state: Shandong
city: Rizhao
country: China
facility: Rizhao People's Hospital
state: Shandong
city: Rizhao
country: China
facility: Rizhao Traditional Chinese Medicine Hospital
state: Shandong
city: Linfen
country: China
facility: Linfen Central Hospital
state: Shanxi
Study officials:
affiliation: Linyi People's Hospital
name: Fengyuan Che, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Tiantan Hospital
name: Yunyun Xiong, MD
role: PRINCIPAL_INVESTIGATOR
References: