Tenecteplase before transfer for anterior circulation large-vessel stroke (4.5–24 hours)

Tenecteplase Before inteRhospital Transfer for Endovascular Treatment in pAtientS With acUte Anterior ciRculation Large vEssel Occlusion at 4.5 to 24 Hours

This will test whether a single bolus of tenecteplase given at the first hospital before transfer helps people with anterior circulation large-vessel ischemic stroke who present 4.5–24 hours after they were last well.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 572 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Xuanwu Hospital, Beijing (Academic / other)
• Locations: 2 sites (Beijing, Beijing Municipality and 1 other locations)
• Trial ID: NCT07253181 on ClinicalTrials.gov

What this trial studies

Adults with anterior circulation large-vessel occlusion who present 4.5 to 24 hours after last known well and have a favorable perfusion mismatch are randomized at non-endovascular-capable hospitals to receive a single bolus of tenecteplase (0.25 mg/kg, max 25 mg) or standard care before transfer for endovascular treatment. The tenecteplase dose is given as a single bolus and patients are then transferred to an endovascular-capable center for EVT. The study's primary focus is on efficacy and safety of pre-transfer tenecteplase compared with current practice, and a key secondary goal is to analyze how time from needle-to-arterial puncture affects outcomes. Outcomes include reperfusion, functional status, and safety endpoints after EVT.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) with anterior circulation ICA/M1/M2 occlusion, NIHSS 6–25, pre-stroke mRS 0–2, presenting 4.5–24 hours from last known well with a target perfusion mismatch and planned transfer for EVT.

Not a fit: Patients unlikely to benefit include those outside the 4.5–24 hour window, with large ischemic core (e.g., core volume ≥70 mL), posterior circulation strokes, major preexisting disability, or standard contraindications to thrombolysis.

Why it matters

Potential benefit: If successful, giving tenecteplase before transfer could increase early reperfusion and improve functional outcomes while not delaying endovascular treatment.

How similar studies have performed: Previous trials have shown tenecteplase can be at least as effective as alteplase and may improve reperfusion before EVT in earlier time windows, but administering tenecteplase specifically at non-ECC sites in the 4.5–24 hour transfer setting is less well studied.

Eligibility criteria

Inclusion Criteria:

* Age of 18 years or older;
* AIS symptom onset to treatment initiation within 4.5 to 24 hours, stroke onset is defined as the time the patient was last known to be well (including wake-up stroke and unwitnessed stroke);
* Signs and symptoms consistent with the diagnosis of an acute anterior circulation ischemic stroke involving occlusion of the internal carotid artery (ICA), MCA (M1 or M2) vessels;
* Functionally independent (mRS 0-2) prior to stroke onset;
* Baseline National Institute of Health Stroke Scale (NIHSS) of 6-25;
* Intended to transfer to ECCs for EVT (patient transfer), or intended to transfer a neurointerventionalist from the ECC for EVT (physician transfer);
* Written informed consent from patients or legally authorized representatives;
* Neuroimaging: ICA or M1, M2 occlusion by MRA or CTA AND the target mismatch profile on computed tomography perfusion (CTP) or magnetic resonance perfusion (MRP), defined as an ischemic core volume \<70mL, mismatch volume ≥15mL and mismatch ratio ≥1.8;

Alternative neuroimaging (if CTP or MRP is technically inadequate or unavailable):

The presence of a diffusion-weighted imaging (DWI)-fluid-attenuated inversion recovery (FLAIR) mismatch pattern (i.e., acute ischemic lesion visible on DWI but no marked parenchymal hyperintensity visible on FLAIR) OR an Alberta Stroke Program Early CT Score (ASPECTS) score ≥7 on NCCT or MRI scan;

Exclusion Criteria:

* Known hypersensitivity or allergy to any ingredients of Tenecteplase;
* Intended to receive IVT as standard-of-care therapy;
* Rapidly improving symptoms with NIHSS score \<6 before randomization;
* Any contra-indication for IVT except for the time criterion;
* Known hereditary or acquired hemorrhagic diathesis;
* Impairment in coagulation due to comorbid disease or anticoagulant use. If on warfarin, INR \>1.7 or prothrombin time \>15s; if use of any direct oral anticoagulant within the last 48 hours; if on any full dose heparin/heparinoid within the last 24 hours;
* Ischemic stroke or myocardial infarction in previous 3 months
* Previous intracranial hemorrhage, active internal bleeding (gastrointestinal or urinary tract hemorrhage) in previous 3 months;
* Severe, uncontrolled hypertension (systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg);
* Other serious, advanced or terminal illness with life expectancy less than 6 months;
* Baseline blood glucose \<50mg/dl or \>400mg/dl;
* Contraindication to imaging with contrast agents;
* Acute symptomatic arterial occlusions in more than one vascular territory confirmed on CTA or MRA (e.g. bilateral MCA occlusions, or an MCA and a basilar artery occlusion);
* Extensive early ischemic change on non-contrast CT or MRI-DWI estimated to be \>1/3 MCA territory, or significant hypodensity outside the Tmax\>6s perfusion lesion that invalidates mismatch criteria (if patient is enrolled based on CT perfusion criteria);
* Evidence of intracranial tumor (mass effect), acute intracranial hemorrhage, or arteriovenous malformation;
* Current participation in another investigational drug or device study;
* Suspected endocarditis;
* Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study;

Where this trial is running

Beijing, Beijing Municipality and 1 other locations

• Xuanwu Hospital Capital Medical University — Beijing, Beijing Municipality, China (Recruiting)
• Affiliated Hospital of Shandong Second Medical University — Weifang, Shandong, China (Recruiting)

Study contacts

• Principal investigator: Junwei Hao, MD, PhD — Xuanwu Hospital, Beijing
• Study coordinator: Gaoting Ma, MD

Conditions Acute Ischemic Stroke; Large Vessel Occlusion; Transportation of Patients; interhospital transfer; acute ischemic stroke; anterior circulation large vessel occlusion