Intra-arterial tenecteplase given after thrombectomy for anterior large-vessel ischemic stroke with no-reflow or residual clot
Post-thrombectomy Intra-arterial Tenecteplase for Acute manaGement of Non-retrievable Thrombus and No-reflow in Emergent Stroke (EXTEND-AGNES TNK)
This trial will test whether giving tenecteplase directly into the artery at the end of thrombectomy helps people with anterior large-vessel ischemic stroke treated within 24 hours of symptom onset.
Quick facts
| Phase | Phase2; Phase3 |
|---|---|
| Study type | Interventional |
| Enrollment | 462 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University of Melbourne Academic / other |
| Drugs / interventions | idarucizumab |
| Locations | 13 sites (Gold Coast, Queensland and 12 other locations) |
| Trial ID | NCT05892510 on ClinicalTrials.gov |
What this trial studies
This is a multicenter, randomized, double-blind, placebo-controlled seamless phase 2b/3 trial using a two-arm (1:1) design to compare intra-arterial tenecteplase versus placebo delivered at the completion of mechanical thrombectomy. Eligible participants are adults with anterior circulation large-vessel occlusion (intracranial ICA, M1, or proximal M2) treated within 24 hours and meeting imaging criteria (ASPECTS ≥3 or core <100 mL for the 6–24 hour window). The intervention is an intra-arterial injection administered after the thrombectomy procedure to target residual non-retrievable thrombus or no-reflow. The trial will measure safety and efficacy outcomes including reperfusion measures and clinical functional recovery.
Who should consider this trial
Good fit: Adults (age ≥18) with anterior circulation large-vessel occlusion planned for mechanical thrombectomy within 24 hours, with ASPECTS ≥3 (or core <100 mL if 6–24 h), and pre-stroke mRS ≤2 are ideal candidates.
Not a fit: Patients with intracranial hemorrhage, very low ASPECTS (0–2), a large ischemic core (>100 mL), posterior circulation strokes, those not undergoing thrombectomy, or those outside the treatment window are unlikely to benefit.
Why it matters
Potential benefit: If successful, the approach could improve reperfusion and functional recovery after thrombectomy by dissolving residual clot and resolving no-reflow, potentially reducing disability.
How similar studies have performed: Previous work has shown benefit for intravenous tenecteplase in some stroke settings and small trials have tested intra-arterial thrombolytics, but intra-arterial tenecteplase at thrombectomy completion is a relatively novel approach without large definitive randomized evidence yet.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Adult participants (age≥18 years) presenting with ischemic stroke with arterial LVO on CT/MR Angiogram of the intracranial internal carotid or middle cerebral artery (MCA) first segment (M1) or proximal second segment (M2) committed to thrombectomy using standard criteria within 24 hours of onset: * For 0-6 hours of symptom onset: Presence of arterial occlusion as defined above and ASPECTS≥3 on NCCT * For 6-24 hours of symptom onset: Additional imaging criteria on CTP or MRI perfusion of core volume \<100ml. * Qualifying CT/MR within 4hrs of randomisation (repeat CT for transferred participants required if \>4hr) * Pre-stroke Modified Rankin Scale (mRS) score of ≤2 (mild pre-existing disability permitted) * Local legal requirements for consent have been satisfied. Exclusion Criteria: * Intracranial hemorrhage identified by CT or MRI * ASPECTS 0-2 on NCCT * CTP or MRI perfusion ischemic core volume \>100ml if presenting within 6-24 hours from symptoms onset * Anticipated endovascular stenting required for intracranial or extracranial atherosclerotic stenosis/occlusion. * More than six retrieval attempts in the same vessel * Alteplase being infused within 30 minutes (\~5x half-life) of anticipated trial drug administration * Contraindication to imaging with contrast agents * Any condition (eg.mid-arterial phase early venous filling) that in the judgment of investigators could impose hazards if study therapy is initiated * Pregnant women. * Current participation in another intervention research study that includes experimental interventions beyond standard-of-care. * Anticoagulation. INR ≤1.7 if on warfarin, and dabigatran reversal by idarucizumab are permitted. * Other standard contraindications to thrombolysis apart from time window. * Known terminal illness such that the participants would not be expected to survive a year. * Planned withdrawal of care or comfort care measures.
Where this trial is running
Gold Coast, Queensland and 12 other locations
- Gold Coast Univeristy Hospital — Gold Coast, Queensland, Australia (Recruiting)
- Royal Adelaide Hospital — Adelaide, Australia (Recruiting)
- Princess Alexandra Hospital — Brisbane, Australia (Not_yet_recruiting)
- Royal Brisbane and Women's Hospital — Brisbane, Australia (Not_yet_recruiting)
- Canberra Hospital — Canberra, Australia (Not_yet_recruiting)
- Alfred Hospital — Melbourne, Australia (Recruiting)
- Austin Hospital — Melbourne, Australia (Recruiting)
- Monash Medical Centre — Melbourne, Australia (Not_yet_recruiting)
- Royal Melbourne Hospital — Melbourne, Australia (Recruiting)
- John Hunter Hospital — Newcastle, Australia (Not_yet_recruiting)
- Fiona Stanley Hospital — Perth, Australia (Not_yet_recruiting)
- Liverpool Hospital — Sydney, Australia (Not_yet_recruiting)
- Royal North Shore Hospital — Sydney, Australia (Not_yet_recruiting)
Study contacts
- Study coordinator: Felix Ng
- Email: ng.f@unimelb.edu.au
- Phone: +03 9342 7000
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.