RecruitingPhase 2Phase 3NCT05105633

Extending the Time Window for Tenecteplase by Recanalization of Basilar Artery Occlusion in Posterior Circulation Stroke

Extending the Time Window for Tenecteplase by Effective RecanalizatioN of bAsilar Artery occLusion in Patients With POSTerior Circulation Stroke (POST-ETERNAL)


Sponsor

University of Melbourne

Enrollment

688 participants

Start Date

Nov 29, 2021

Study Type

INTERVENTIONAL

Conditions

Summary

Patients presenting to the emergency department with an acute ischemic stroke due to basilar artery occlusion within 24 hours of stroke onset will be assessed to determine their eligibility for randomization into the trial. If the patient gives informed consent they will be randomised 50:50 using a central computerised allocation process to either standard of care (no intravenous thrombolytic treatment or intravenous alteplase 0.9mg/kg) or tenecteplase 0.25mg/kg before undergoing mechanical thrombectomy as required at treating clinician's discretion. The trial is Multi-arm, Multi-stage, prospective, randomised, open-label, blinded endpoint (PROBE) design with seamless phase 2b/3 transition if the intermediate endpoint (recanalization without symptomatic intracerebral hemorrhage) is met in analysis of the first 202 patients. Adaptive sample size re-estimation (Mehta and Pocock) will be performed when 240 patients have completed 3 month follow-up (minimum sample size 320, maximum sample size 688).


Eligibility

Min Age: 18 Years

Inclusion Criteria5

  • Patients presenting with posterior circulation ischemic stroke symptoms due to partial or complete basilar artery occlusion within 24 hours from symptom onset (or clinical deterioration/coma) or the time the patient was last known to be well.
  • Patient's age is ≥18 years
  • Presence of basilar artery occlusion, proven by CT Angiography or MR Angiography. Basilar artery occlusion is defined as 'potentially retrievable' occlusion at the basilar artery. This can be a partial or complete occlusion.
  • Premorbid mRS ≤3 (independent function or requiring only minor domestic assistance and able to manage alone for at least 1 week).
  • Local legal requirements for consent have been satisfied.

Exclusion Criteria14

  • Intracerebral hemorrhage (ICH) or other diagnosis (e.g. tumour) identified by baseline imaging.
  • Posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS) \<7 on non-contrast CT, CT Angiography source images or DWI MRI.
  • Significant cerebellar mass effect or acute hydrocephalus.
  • Established frank hypodensity on non-contrast CT indicating subacute infarction.
  • Bilateral extensive brainstem ischemia.
  • Strong suspicion of underlying intracranial atherosclerotic disease (e.g diffuse arterial calcifications, basilar stenosis) or dissection which may require immediate neuro-interventional procedure with intracranial stenting and not benefit from intravenous thrombolysis at investigator's discretion.
  • Pre-stroke mRS of ≥4 (indicating moderate to severe previous disability).
  • Other standard contraindications to intravenous thrombolysis.
  • Contraindication to imaging with contrast agents.
  • Clinically evident pregnant women.
  • Current participation in another research drug treatment protocol.
  • Known terminal illness such that the patients would not be expected to survive a year.
  • Planned withdrawal of care or comfort care measures.
  • 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.

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Interventions

DRUGTenecteplase

Genetically modified tissue plasminogen activator at a dose of 0.25mg/kg given as an intravenous bolus over 5-10 seconds.

DRUGStandard Care (which may include intravenous Alteplase)

Patients will receive standard care which may include intravenous alteplase at the standard licensed dose of 0.9 mg/kg up to a maximum of 90mg, 10% as a bolus and the remainder as an infusion over 1 hour.


Locations(13)

Bankstown-Lidcombe Hospital

Bankstown, New South Wales, Australia

John Hunter Hospital

Newcastle, New South Wales, Australia

Liverpool Hospital

Sydney, New South Wales, Australia

Gold Coast Hospital

Gold Coast, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Alfred Health

Melbourne, Victoria, Australia

Austin Hospital

Melbourne, Victoria, Australia

Box Hill Hospital

Melbourne, Victoria, Australia

Monash Health

Melbourne, Victoria, Australia

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Western Health

Melbourne, Victoria, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

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