RecruitingPhase 2Phase 3NCT05892510

Post-thrombectomy Intra-arterial Tenecteplase for Acute manaGement of Non-retrievable Thrombus and No-reflow in Emergent Stroke

Post-thrombectomy Intra-arterial Tenecteplase for Acute manaGement of Non-retrievable Thrombus and No-reflow in Emergent Stroke (EXTEND-AGNES TNK)


Sponsor

University of Melbourne

Enrollment

462 participants

Start Date

Jun 1, 2024

Study Type

INTERVENTIONAL

Conditions

Summary

Multicentre, prospective, Multi-arm Multi-stage (MAMS) seamless phase 2b/3 interventional randomized placebo-controlled double-blinded parallel-assignment (2 arms with 1:1 randomization) efficacy and safety trial to test intra-arterial tenecteplase at the completion of thrombectomy versus best practice in participants with anterior circulation LVO receiving mechanical thrombectomy within 24 hours of symptoms onset.


Eligibility

Min Age: 18 Years

Inclusion Criteria6

  • 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 Criteria14

  • 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.

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Interventions

DRUGIntra-arterial tenecteplase injection at the completion of thrombectomy

Intra-arterial tenecteplase (0.062mg/kg, maximum 6.25mg) administered as a bolus at the completion of thrombectomy through a microcatheter at the site of the initial-but-now-retrieved intracranial occlusion, or in direct contact with the residual thrombus

DRUGPlacebo

intra-arterial bolus of 0.9% Sodium Chloride solution


Locations(13)

Gold Coast Univeristy Hospital

Gold Coast, Queensland, Australia

Royal Adelaide Hospital

Adelaide, Australia

Princess Alexandra Hospital

Brisbane, Australia

Royal Brisbane and Women's Hospital

Brisbane, Australia

Canberra Hospital

Canberra, Australia

Alfred Hospital

Melbourne, Australia

Austin Hospital

Melbourne, Australia

Monash Medical Centre

Melbourne, Australia

Royal Melbourne Hospital

Melbourne, Australia

John Hunter Hospital

Newcastle, Australia

Fiona Stanley Hospital

Perth, Australia

Liverpool Hospital

Sydney, Australia

Royal North Shore Hospital

Sydney, Australia

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NCT05892510


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