Extending the Time Window for Tenecteplase by Recanalization of Basilar Artery Occlusion in Posterior Circulation Stroke (POST-ETERNAL)

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

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).

Study Overview

• Status: Recruiting
• Conditions: Basilar Artery Occlusion
• Intervention / Treatment: Drug: Tenecteplase; Drug: Standard Care (which may include intravenous Alteplase)

Detailed Description

The study is a Multi-Arm Multi-Stage (MAMS), multiregional, multicentre, prospective, randomised, open-label, blinded endpoint (PROBE), controlled seamless phase 2b/3 trial (2 arm with 1:1 randomisation) with adaptive sample size recalculation in patients with stroke due to basilar artery occlusion. Stage 1 will use the surrogate outcome of recanalization without symptomatic intracerebral hemorrhage (sICH) to establish whether proceeding to Stage 2 is warranted. If results in the first n= 202 patients meet success criteria, the trial will seamlessly convert to a phase 3 design using modified Rankin scale 0-1 at 3 months as the primary outcome (minimum n=320 with interim sample size re-estimation at n=240, maximum sample n=688) using the Mehta and Pocock conditional power method. Each regionally-based stratum will be pooled in the final analysis and analysed as a stratification by geographic region. Randomisation of patients within each stratum will be stratified by the investigator's intention to treat with mechanical thrombectomy (or not) and the investigator's intention to treat with alteplase intravenous thrombolysis should the patient be randomised to the control group (or not). Covariate adjusted minimum sufficient balance randomisation will then be applied to control for age, NIHSS and time from onset-to-randomisation (dichotomized as 0-6 hours vs 6-24 hours). The primary objective of the study is to test the hypothesis that the thrombolytic tenecteplase (TNK, 0.25mg/kg) ± mechanical thrombectomy administered within 24 hours after symptoms onset, is superior to current best practice (alteplase, rtPA, 0.9mg/kg or standard care/no lysis ± mechanical thrombectomy) in achieving excellent functional outcome (mRS 0-1) or return to the premorbid modified Rankin Scale at 90 days in patients with acute ischemic stroke due to basilar artery occlusion. Estimated study duration is 5 years. Patients will participate in the trial for 12 months.

• Study Type: Interventional
• Enrollment (Estimated): 688
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Fana Alemseged, MD, PhD; Phone Number: +6193424424; Email: Fana.Alemseged@unimelb.edu.au
• Study Contact Backup: Name: Erin White; Email: erin.white@florey.edu.au

Study Locations

• Australia
  • Ballarat, Australia
    • Recruiting
    • Grampians Health
    • Contact: Melbin Samuvel; Phone Number: +61(03) 53305104; Email: Melbin.Samuvel@gh.org.au
  • Melbourne, Australia
    • Recruiting
    • Northern Hospital
    • Contact: Douglas Crompton; Phone Number: +61(03) 8405 8000
  • New South Wales
    • Bankstown, New South Wales, Australia
      • Not yet recruiting
      • Bankstown-Lidcombe Hospital
      • Contact: Megan Miller
      • Principal Investigator: Fintan O' Rourke
    • Newcastle, New South Wales, Australia
      • Not yet recruiting
      • John Hunter Hospital
      • Contact: Michelle Russell
      • Principal Investigator: Carlos Garcia Esperon
    • Sydney, New South Wales, Australia
      • Recruiting
      • Liverpool Hospital
      • Principal Investigator: Dennis Cordato
      • Contact: Timmy Pham; Email: timmy.pham@health.nsw.gov.au
  • Queensland
    • Gold Coast, Queensland, Australia
      • Not yet recruiting
      • Gold Coast Hospital
      • Contact: Berzenn Urbi
      • Principal Investigator: Peter Bailey
    • Woolloongabba, Queensland, Australia, 4102
      • Recruiting
      • Princess Alexandra Hospital
      • Principal Investigator: Michael Devlin
      • Contact: Carol Bendall
  • South Australia
    • Adelaide, South Australia, Australia
      • Recruiting
      • Royal Adelaide Hospital
      • Contact: Jennifer Cranefield
      • Principal Investigator: Timothy Kleinig
  • Victoria
    • Melbourne, Victoria, Australia
      • Recruiting
      • Royal Melbourne Hospital
      • Contact: Amy McDonald, BN; Phone Number: +619342 4424; Email: amy.mcdonald@mh.org.au
      • Principal Investigator: Bruce Campbell
    • Melbourne, Victoria, Australia
      • Recruiting
      • Box Hill Hospital
      • Contact: Tessa Busch
      • Principal Investigator: Philip Choi
    • Melbourne, Victoria, Australia
      • Recruiting
      • Austin Hospital
      • Principal Investigator: Vincent Thijs
      • Contact: Joanne Dimovitis; Email: joanne.dimovitis@austin.org.au
    • Melbourne, Victoria, Australia
      • Not yet recruiting
      • Monash Health
      • Contact: Marie Veronic Hervet
      • Principal Investigator: Shaloo Singhal
    • Melbourne, Victoria, Australia
      • Recruiting
      • Alfred Health
      • Contact: Andrea Moore
      • Principal Investigator: Geoffrey Cloud
    • Melbourne, Victoria, Australia
      • Recruiting
      • Western Health
      • Contact: Sherisse Celestino
      • Principal Investigator: Tissa Wijeratne
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Recruiting
      • Fiona Stanley Hospital
      • Principal Investigator: Darshan Ghia
      • Contact: Phoebe Lee
• Brazil
  • Fortaleza, Brazil
    • Recruiting
    • Hospital Geral de Fortaleza
    • Contact: Maria Samara Souza; Phone Number: +55 (85) 991969752; Email: mariasamarasouza32@gmail.com
    • Principal Investigator: Francisco Mont'Alverne
• France
  • Tours, France
    • Recruiting
    • Tours University Hospital
    • Contact: Yoann DESVIGNES; Phone Number: +33247474632; Email: y.desvignes@chu-tours.fr
    • Principal Investigator: Marco PASI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous tenecteplase (TNK); Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over 5-10 seconds).	Drug: Tenecteplase; Genetically modified tissue plasminogen activator at a dose of 0.25mg/kg given as an intravenous bolus over 5-10 seconds.
Active Comparator: Standard Care (which may include intravenous Alteplase); Patients will receive standard of care (no intravenous thrombolytic treatment or intravenous alteplase 0.9mg/kg 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).	Drug: Standard 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale (mRS) 0-1 or return to baseline mRS at 90 days	Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS (if baseline premorbid mRS 2-3) at 90 days	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality within 90 days	All-cause mortality within 90 days	90 days
Modified Rankin Scale 0-2 or return to baseline mRS at 90 days	Proportion of patients with Modified Rankin Scale 0-2 or return to baseline mRS at 90 days	90 days
Modified Rankin Scale 0-3 or return to baseline mRS at 90 days	Proportion of patients with Modified Rankin Scale 0-3 or return to baseline mRS at 90 days	90 days
Ordinal analysis of the mRS at 90 days	Ordinal analysis of the mRS, merging category 5-6, at 90 days	90 days
Early clinical improvement	Proportion of patients achieving early clinical improvement (reduction in acute - 72 hour NIHSS score of ≥8 or 72 hour NIHSS 0-1).	72 hours
Substantial reperfusion on initial digital subtraction angiography run prior to thrombectomy	Proportion of patients with complete occlusion at baseline who achieve eTICI 2b/3 on initial digital subtraction angiography run prior to thrombectomy.	Initial angiogram (day 0)
Quality of Life assessment (EQ-5D) - at 90 days and 12 months	Quality of Life assessment (EQ-5D) - at 90 days and 12 months	90 days and 12 months
Symptomatic intracerebral hemorrhage (sICH)	Proportion of patients with sICH defined as parenchymal hemorrhage type 2 (PH2), subarachnoid hemorrhage, and/or intraventricular hemorrhage within 36 of treatment, combined with a neurological deterioration of ≥4 points on the NIHSS from baseline, or leading to death.	36 hours
Modified Rankin Scale (mRS) 5-6 at 90 days	Proportion of patients with Modified Rankin Scale (mRS) 5-6 at 90 days (severe disability or death)	90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intermediate outcome (Stage 1): Partial or complete recanalization of the basilar artery without sICH	Proportion of patients achieving partial or complete recanalization of the basilar artery on initial digital subtraction angiography (DSA) prior to thrombectomy or repeat CT Angiography (if DSA not performed) without symptomatic intracerebral hemorrhage (sICH). Partial or complete recanalization is defined as reperfusion of ≥50% of the affected territory or absence of retrievable thrombus.	Initial angiogram (day 0)

Collaborators and Investigators

• Sponsor: University of Melbourne
• Investigators: Principal Investigator: Bruce Campbell, University of Melbourne; Principal Investigator: Fana Alemseged, University of Melbourne

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2021
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: October 21, 2021
• First Submitted That Met QC Criteria: October 21, 2021
• First Posted (Actual): November 3, 2021

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Stroke; Vascular Diseases; Cardiovascular Diseases; Nervous System Diseases; ischemic stroke; Central Nervous System Diseases; Brain Diseases; Cerebrovascular Disorders; Molecular Mechanisms of Pharmacological Action; Tissue Plasminogen Activator; Tenecteplase; Fibrin Modulating Agents; basilar artery occlusion
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Ischemic Stroke; Stroke; Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Nervous System Diseases; Central Nervous System Diseases; Cerebrovascular Disorders; Health Services Administration; Health Care Quality, Access, and Evaluation; Amino Acids, Peptides, and Proteins; Proteins; Quality of Health Care; Quality Indicators, Health Care; Hydrolases; Enzymes; Enzymes and Coenzymes; Blood Proteins; Endopeptidases; Peptide Hydrolases; Serine Endopeptidases; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Tissue Plasminogen Activator; Tenecteplase; Standard of Care
• Other Study ID Numbers: CT21028

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient data will be uploaded to the Virtual Stroke Trials Archive 2 years after the publication of the primary manuscript. Qualified investigators can access data after submission of a project proposal that has been approved by the VISTA steering committee.
• IPD Sharing Time Frame: 2 years after the publication of the primary manuscript.
• IPD Sharing Access Criteria: Qualified investigators can access data after submission of a project proposal that has been approved by the VISTA steering committee.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No