search
Back to results

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

Primary Purpose

Basilar Artery Occlusion

Status
Recruiting
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
Tenecteplase
Standard Care (which may include intravenous Alteplase)
Sponsored by
University of Melbourne
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Basilar Artery Occlusion focused on measuring ischemic stroke, basilar artery occlusion, Stroke, Tenecteplase, Tissue Plasminogen Activator, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Vascular Diseases, Cardiovascular Diseases, Fibrin Modulating Agents, Molecular Mechanisms of Pharmacological Action

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Bankstown-Lidcombe Hospital
  • John Hunter Hospital
  • Liverpool Hospital
  • Gold Coast Hospital
  • Royal Adelaide HospitalRecruiting
  • Alfred Health
  • Austin Hospital
  • Box Hill HospitalRecruiting
  • Monash Health
  • Royal Melbourne HospitalRecruiting
  • Western Health

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Intravenous tenecteplase (TNK)

Standard Care (which may include intravenous Alteplase)

Arm Description

Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over 5-10 seconds).

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).

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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
Ordinal analysis of the mRS at 90 days
Ordinal analysis of the mRS, merging category 5-6, at 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).
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.
Quality of Life assessment (EQ-5D) - at 90 days and 12 months
Quality of Life assessment (EQ-5D) - at 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.
All-cause mortality within 90 days
All-cause mortality within 90 days
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)

Full Information

First Posted
October 21, 2021
Last Updated
May 29, 2022
Sponsor
University of Melbourne
search

1. Study Identification

Unique Protocol Identification Number
NCT05105633
Brief Title
Extending the Time Window for Tenecteplase by Recanalization of Basilar Artery Occlusion in Posterior Circulation Stroke
Acronym
POST-ETERNAL
Official Title
Extending the Time Window for Tenecteplase by Effective RecanalizatioN of bAsilar Artery occLusion in Patients With POSTerior Circulation Stroke (POST-ETERNAL)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 29, 2021 (Actual)
Primary Completion Date
August 2026 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Melbourne

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Basilar Artery Occlusion
Keywords
ischemic stroke, basilar artery occlusion, Stroke, Tenecteplase, Tissue Plasminogen Activator, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Vascular Diseases, Cardiovascular Diseases, Fibrin Modulating Agents, Molecular Mechanisms of Pharmacological Action

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Patients will receive either intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over 5-10 seconds) or standard of care (alteplase 0.9mg/kg or no lysis) +/- mechanical thrombectomy
Masking
None (Open Label)
Allocation
Randomized
Enrollment
688 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intravenous tenecteplase (TNK)
Arm Type
Experimental
Arm Description
Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over 5-10 seconds).
Arm Title
Standard Care (which may include intravenous Alteplase)
Arm Type
Active Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Tenecteplase
Intervention Description
Genetically modified tissue plasminogen activator at a dose of 0.25mg/kg given as an intravenous bolus over 5-10 seconds.
Intervention Type
Drug
Intervention Name(s)
Standard Care (which may include intravenous Alteplase)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Modified Rankin Scale (mRS) 0-1 or return to baseline mRS at 90 days
Description
Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS (if baseline premorbid mRS 2-3) at 90 days
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Modified Rankin Scale 0-2 or return to baseline mRS at 90 days
Description
Proportion of patients with Modified Rankin Scale 0-2 or return to baseline mRS at 90 days
Time Frame
90 days
Title
Modified Rankin Scale 0-3 or return to baseline mRS at 90 days
Description
Proportion of patients with Modified Rankin Scale 0-3 or return to baseline mRS at 90 days
Time Frame
90 days
Title
Ordinal analysis of the mRS at 90 days
Description
Ordinal analysis of the mRS, merging category 5-6, at 90 days
Time Frame
90 days
Title
Early clinical improvement
Description
Proportion of patients achieving early clinical improvement (reduction in acute - 72 hour NIHSS score of ≥8 or 72 hour NIHSS 0-1).
Time Frame
72 hours
Title
Substantial reperfusion on initial digital subtraction angiography run prior to thrombectomy
Description
Proportion of patients with complete occlusion at baseline who achieve eTICI 2b/3 on initial digital subtraction angiography run prior to thrombectomy.
Time Frame
Initial angiogram (day 0)
Title
Quality of Life assessment (EQ-5D) - at 90 days and 12 months
Description
Quality of Life assessment (EQ-5D) - at 90 days and 12 months
Time Frame
90 days and 12 months
Title
Symptomatic intracerebral hemorrhage (sICH)
Description
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.
Time Frame
36 hours
Title
All-cause mortality within 90 days
Description
All-cause mortality within 90 days
Time Frame
90 days
Title
Modified Rankin Scale (mRS) 5-6 at 90 days
Description
Proportion of patients with Modified Rankin Scale (mRS) 5-6 at 90 days (severe disability or death)
Time Frame
90 days
Other Pre-specified Outcome Measures:
Title
Intermediate outcome (Stage 1): Partial or complete recanalization of the basilar artery without sICH
Description
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.
Time Frame
Initial angiogram (day 0)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fana Alemseged, MD, PhD
Phone
+6193424424
Email
Fana.Alemseged@unimelb.edu.au
First Name & Middle Initial & Last Name or Official Title & Degree
Amy McDonald, BN
Phone
+6193424424
Email
Amy.McDonald@mh.org.au
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruce Campbell
Organizational Affiliation
University of Melbourne
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Fana Alemseged
Organizational Affiliation
University of Melbourne
Official's Role
Principal Investigator
Facility Information:
Facility Name
Bankstown-Lidcombe Hospital
City
Bankstown
State/Province
New South Wales
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Megan Miller
First Name & Middle Initial & Last Name & Degree
Fintan O' Rourke
Facility Name
John Hunter Hospital
City
Newcastle
State/Province
New South Wales
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michelle Russell
First Name & Middle Initial & Last Name & Degree
Carlos Garcia Esperon
Facility Name
Liverpool Hospital
City
Sydney
State/Province
New South Wales
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Megan Miller
First Name & Middle Initial & Last Name & Degree
Mark Parsons
Facility Name
Gold Coast Hospital
City
Gold Coast
State/Province
Queensland
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Berzenn Urbi
First Name & Middle Initial & Last Name & Degree
Peter Bailey
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Cranefield
First Name & Middle Initial & Last Name & Degree
Timothy Kleinig
Facility Name
Alfred Health
City
Melbourne
State/Province
Victoria
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Moore
First Name & Middle Initial & Last Name & Degree
Geoffrey Cloud
Facility Name
Austin Hospital
City
Melbourne
State/Province
Victoria
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dennis Young
First Name & Middle Initial & Last Name & Degree
Vincent Thijs
Facility Name
Box Hill Hospital
City
Melbourne
State/Province
Victoria
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tessa Busch
First Name & Middle Initial & Last Name & Degree
Philip Choi
Facility Name
Monash Health
City
Melbourne
State/Province
Victoria
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie Veronic Hervet
First Name & Middle Initial & Last Name & Degree
Shaloo Singhal
Facility Name
Royal Melbourne Hospital
City
Melbourne
State/Province
Victoria
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amy McDonald, BN
Phone
+619342 4424
Email
amy.mcdonald@mh.org.au
First Name & Middle Initial & Last Name & Degree
Bruce Campbell
Facility Name
Western Health
City
Melbourne
State/Province
Victoria
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sherisse Celestino
First Name & Middle Initial & Last Name & Degree
Tissa Wijeratne

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
https://www.virtualtrialsarchives.org/vista/

Learn more about this trial

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

We'll reach out to this number within 24 hrs