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Ischemic StrokePhase 3ETERNAL-LVONCT04454788

Extending the Time Window for Tenecteplase by Effective Reperfusion in Patients with Large Vessel Occlusion

A Phase 3 study testing Tenecteplase in people with Ischemic Stroke, run by University of Melbourne at 7 sites in Australia.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Patients presenting to the emergency department with an acute ischemic stroke due to a large vessel occlusion eligible for thrombectomy and target mismatch on computed tomography perfusion imaging within 24 hours of onset will be assessed determine their eligibility for randomization into the trial. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Ischemic Stroke
What is being tested?
Tenecteplase
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
242 participants
Where
7 sitesAustralia
Study dates
1 Aug 2020to 6 Jan 2025
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients presenting with acute hemispheric ischemic stroke with onset (or the time they last known to be well) within 24 hours.
  • Patient's age is ≥18 years.
  • Premorbid mRS <3, with a concurrent assessment of whether the patient was able, immediately prior to the stroke, to: 1) Drive, or (if never drives) perform own Domestic duties, and 2) Shop for themselves, and 3) Bank/do their own finances (i.e. Drive/Domestic, Bank, Shop = DBS +ve). Need to be DBS +ve to be study eligible.
  • Presence of a vessel occlusion on CTA or MRA. LVO will be defined as 'potentially retrievable' thrombus at one or more of the following sites: intracranial internal carotid (ICA), middle cerebral artery (MCA) first segment (M1), proximal middle cerebral artery second segment (M2) or isolated/tandem occlusion of the extracranial ICA. Patients with an extracranial ICA stenosis and occlusion are also eligible.
  • Presence of 'target mismatch' on automated perfusion CT (CTP) or diffusion-perfusion MRI software defined as an ischemic core of <70mL, penumbra of >20mL and an ischemic core to perfusion lesion ratio of >1.8

Who cannot join

  • Intracranial hemorrhage (ICH) or other diagnosis (e.g. tumor).
  • Basilar Artery occlusion.
  • Extensive early ischemic change (hypodensity on NCCT or high signal on DWI-MRI) or early ischemic change outside the perfusion lesion that invalidates mismatch criteria.
  • Pre-stroke mRS score of > 2 (indicating significant previous disability) or DBS -ve.
  • Any terminal illness such that patient would not be expected to survive more than 1 year
  • 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.
Show all 19Show fewer
  • Pregnant women.
  • Other standard contraindications to thrombolysis.
  • Minor stroke symptoms, or major stroke symptoms rapidly improving
  • Clinical presentation suggesting subarachnoid haemorrhage
  • Known bleeding diasthesis and/or platelet count <100,000 or taking warfarin with INR > 1.7.
  • Patients who have received heparin within 48 hours must have normal aPTT.
  • Major surgery or serious trauma within 14 days, serious head trauma within 3 months.
  • GI or urinary tract haemorrhage within last 21 days
  • Arterial puncture at a non-compressible site or lumbar puncture within 7 days
  • Systolic BP > 185, diastolic BP > 110mmHg
  • Clinical stroke within 3 months or history of ICH
  • Unable to gain consent from patient or person responsible
  • Known severe renal impairment (GFR < 15mls/min)

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Australia7 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Liverpool Hospital

    Liverpool, New South Wales

  • Royal Melbourne Hospital

    Melbourne, Victoria, 3050

  • Box Hill Hospital

    Melbourne, Victoria

  • John Hunter Hospital

    Newcastle, New South Wales

  • Prince of Wales Hospital

    Randwick, New South Wales

  • Princess Alexandra Hospital

    Woolloongabba, Queensland, 4102

Other trials in Australia

About this study

Official title: Extending the Time Window for Tenecteplase by Effective Reperfusion of PeNumbrAL Tissue in Patients with Large Vessel Occlusion

Patients presenting to the emergency department with an acute ischemic stroke due to a large vessel occlusion eligible for thrombectomy and target mismatch on computed tomography perfusion imaging within 24 hours of onset will be assessed determine their eligibility for randomization into the trial. If the patient gives informed consent they will be randomised using a central computerised allocation process to either standard of care (no intravenous thrombolytic treatment or intravenous alteplase 0.9mg/kg) or tenecteplase before undergoing intra-arterial clot retrieval. The trial is prospective, randomised, open-label, blinded endpoint (PROBE) design.

Conditions
Ischemic Stroke
Being tested
Tenecteplase, Standard Care (which may include intravenous Alteplase)
Medical subject headings
Ischemic Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TenecteplaseDrug

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

  • Standard Care (which may include intravenous Alteplase)Drug

    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 bolus and the remainder over 1 hour.

Study groups in NCT04454788
Study groupRoleWhat they receive
Intravenous tenecteplase (TNK)ExperimentalPatients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over 5-10 seconds).
Receives: Drug: Tenecteplase
Intravenous tissue plasminogen activator (tPA)Active comparatorPatients 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 bolus and the remainder over 1 hour.
Receives: Drug: Standard Care (which may include intravenous Alteplase)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS

    Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS (if baseline premorbid mRS =2) at 90 days

    Measured: 90 days

Secondary outcomes (9)

  1. Early clinical improvement

    Reduction in National Institutes of Health Stroke Scale (NIHSS) score of ≥8 points at 24 hours or reaching NIHSS 0-1

    Measured: 24 hours

  2. Modified Rankin Scale (mRS) 0-2 (functional independence)

    Modified Rankin Scale (mRS) 0-2 (functional independence) at 90 days

    Measured: 90 days

  3. Substantial reperfusion at initial angiographic assessment

    Proportion of patients with >50% reperfusion of the affected vascular territory (mTICI 3b/3) on initial digital subtraction angiography prior to thrombectomy

    Measured: initial angiography within 24 hours of stroke onset

  4. Symptomatic intracerebral hemorrhage (sICH)

    sICH defined as parenchymal hematoma type 2 (PH2) - blood clot occupying >30% of the infarcted territory with substantial mass effect

    Measured: 24 hours post-randomization

  5. Death due to any cause

    Measured: 90 days

  6. Modified Rankin Scale (mRS) 5-6

    Poor functional outcome of death or requirement for fulltime nursing care

    Measured: 90 days

  7. Successful reperfusion at 24 hours

    Reperfusion (defined as >90% and >50% reduction in perfusion lesion volume)

    Measured: 24 hours

  8. Infarct growth

    Increase in the volume of irreversibly injured brain between pre-treatment and 24 hour imaging

    Measured: 24 hours

  9. Recanalization

    Change in vessel patency between pre-treatment and 24h imaging (CT or MR angiography)

    Measured: 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2020
  2. Study start1 Aug 2020
  3. Primary completion28 Jul 2024
  4. Study completion6 Jan 2025

Why it stopped: Loss of equipoise in the 0-4.5h population which comprised the majority of ETERNAL-LVO trial recruitment due to publication of other trials demonstrating efficacy of tenecteplase vs alteplase in the 0-4.5h time window.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
242 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04454788
Sponsor's protocol ID
2019.125
Acronym
ETERNAL-LVO
Status last verified
Jan 2025
First submitted
16 Jun 2020
Last updated
15 Jan 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Yogendrakumar V, Campbell BCV, Churilov L, Garcia-Esperon C, Choi PMC, Cordato DJ, Dhimal N, Olenko L, Guha P, Sharma G, Chen C, McDonald A, Thijs V, Mamun A, Dos Santos A, Balabanski AH, Kleinig TJ, Butcher KS, Devlin MJ, O'Rourke F, Donnan GA, Davis SM, Levi CR, Ma H, Parsons MW; ETERNAL-LVO Investigators. Efficacy of Tenecteplase in Large Vessel Occlusion Stroke Within 24 Hours of Symptom Onset: The ETERNAL-LVO Randomized Controlled Trial. Stroke. 2025 Dec;56(12):3332-3341. doi: 10.1161/STROKEAHA.125.052511. Epub 2025 Sep 10.

    PubMed 40927857

  • Yogendrakumar V, Campbell BC, Churilov L, Garcia-Esperon C, Choi PM, Cordato DJ, Guha P, Sharma G, Chen C, McDonald A, Thijs V, Mamun A, Dos Santos A, Balabanski AH, Kleinig TJ, Butcher KS, Devlin MJ, O'Rourke F, Donnan GA, Davis SM, Levi CR, Ma H, Parsons MW. Extending the time window for tenecteplase by effective reperfusion of penumbral tissue in patients with large vessel occlusion: Rationale and design of a multicenter, prospective, randomized, open-label, blinded-endpoint, controlled phase 3 trial. Int J Stroke. 2025 Mar;20(3):367-372. doi: 10.1177/17474930241308660. Epub 2024 Dec 31.

    PubMed 39654273

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tenecteplase in people with Ischemic Stroke, run by University of Melbourne at 7 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Loss of equipoise in the 0-4.5h population which comprised the majority of ETERNAL-LVO trial recruitment due to publication of other trials demonstrating efficacy of tenecteplase vs alteplase in the 0-4.5h time window.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS (time frame: 90 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04454788, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2025.

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ETERNAL-LVO Clinical Trial NCT04454788 | AzTrials