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

Ischemic Stroke Clinical Trial

— ETERNAL-LVO  

Official title:

Extending the Time Window for Tenecteplase by Effective Reperfusion of peNumbrAL Tissue in Patients With Large Vessel Occlusion

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04454788
• Other study ID #: 2019.125
• Status: Recruiting
• Phase: Phase 3
• Start date: August 1, 2020
• Est. completion date: December 1, 2025

Study information

• Verified date: June 2021
• Source: University of Melbourne
• Contact: Andrew Bivard, PHD
• Phone: +6193424424
• Email: abivard[@]unimelb.edu.au
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 740
• Est. completion date: December 1, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• 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)

Related Conditions & MeSH terms

• Ischemic Stroke

Intervention

Drug:
• Tenecteplase
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)
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.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Box Hill Hospital	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	John Hunter Hospital	Newcastle	New South Wales
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba 4102	Queensland

Sponsors (2)

Lead Sponsor	Collaborator
University of Melbourne	Professor Mark Parsons

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Early clinical improvement	Reduction in National Institutes of Health Stroke Scale (NIHSS) score of =8 points at 24 hours or reaching NIHSS 0-1	24 hours
Secondary	Modified Rankin Scale (mRS) 0-2 (functional independence)	Modified Rankin Scale (mRS) 0-2 (functional independence) at 90 days	90 days
Secondary	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	initial angiography within 24 hours of stroke onset
Secondary	Symptomatic intracerebral hemorrhage (sICH)	sICH defined as parenchymal hematoma type 2 (PH2) - blood clot occupying >30% of the infarcted territory with substantial mass effect	24 hours post-randomization
Secondary	Death due to any cause		90 days
Secondary	Modified Rankin Scale (mRS) 5-6	Poor functional outcome of death or requirement for fulltime nursing care	90 days
Secondary	Successful reperfusion at 24 hours	Reperfusion (defined as >90% and >50% reduction in perfusion lesion volume)	24 hours
Secondary	Infarct growth	Increase in the volume of irreversibly injured brain between pre-treatment and 24 hour imaging	24 hours
Secondary	Recanalization	Change in vessel patency between pre-treatment and 24h imaging (CT or MR angiography)	24 hours