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

NCT04454788 | Terminated Phase 3 DMC

• 1 other identifier: 2019.125
• Study Type: interventional
• Target: 242
• Locations: 1 country
• Sites: 7

Brief 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. 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

Outcome Measures

Primary Outcomes (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

  90 days

Secondary Outcomes (9)

• Early clinical improvement

  24 hours

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

  90 days

• Substantial reperfusion at initial angiographic assessment

  initial angiography within 24 hours of stroke onset

• Symptomatic intracerebral hemorrhage (sICH)

  24 hours post-randomization

• Death due to any cause

  90 days

Study Arms (2)

Intravenous tenecteplase (TNK)

EXPERIMENTAL

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

Drug: Tenecteplase

Intravenous tissue plasminogen activator (tPA)

ACTIVE COMPARATOR

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 bolus and the remainder over 1 hour.

Drug: Standard Care (which may include intravenous Alteplase)

Interventions

Tenecteplase DRUG

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

Intravenous tenecteplase (TNK)

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.

Intravenous tissue plasminogen activator (tPA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• University of Melbourne: lead
• Professor Mark Parsons: collaborator

Study Sites (7)

Liverpool Hospital

Liverpool, New South Wales, Australia

Location

John Hunter Hospital

Newcastle, New South Wales, Australia

Location

Prince of Wales Hospital

Randwick, New South Wales, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

Box Hill Hospital

Melbourne, Victoria, Australia

Location

Related Publications (2)

• 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.

  PMID: 40927857 DERIVED

• 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.

  PMID: 39654273 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Tenecteplase; Standard of Care

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: June 16, 2020
• First Posted: July 2, 2020
• Study Start: August 1, 2020
• Primary Completion: July 28, 2024
• Study Completion: January 6, 2025
• Last Updated: January 15, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (7)