Extending the Time Window for Tenecteplase by Effective Reperfusion in Patients With Large Vessel Occlusion (ETERNAL-LVO)
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|ClinicalTrials.gov Identifier: NCT04454788|
Recruitment Status : Recruiting
First Posted : July 2, 2020
Last Update Posted : June 22, 2021
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|Condition or disease||Intervention/treatment||Phase|
|Ischemic Stroke||Drug: Tenecteplase Drug: Standard Care (which may include intravenous Alteplase)||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||740 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Extending the Time Window for Tenecteplase by Effective Reperfusion of peNumbrAL Tissue in Patients With Large Vessel Occlusion|
|Actual Study Start Date :||August 1, 2020|
|Estimated Primary Completion Date :||June 1, 2025|
|Estimated Study Completion Date :||December 1, 2025|
Experimental: Intravenous tenecteplase (TNK)
Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over 5-10 seconds).
Genetically modified tissue plasminogen activator at a dose of 0.25mg/kg given as intravenous bolus over 5-10 seconds
Active Comparator: Intravenous tissue plasminogen activator (tPA)
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)
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.
- Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS [ Time Frame: 90 days ]Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS (if baseline premorbid mRS =2) at 90 days
- Early clinical improvement [ Time Frame: 24 hours ]Reduction in National Institutes of Health Stroke Scale (NIHSS) score of ≥8 points at 24 hours or reaching NIHSS 0-1
- Modified Rankin Scale (mRS) 0-2 (functional independence) [ Time Frame: 90 days ]Modified Rankin Scale (mRS) 0-2 (functional independence) at 90 days
- Substantial reperfusion at initial angiographic assessment [ Time Frame: initial angiography within 24 hours of stroke onset ]Proportion of patients with >50% reperfusion of the affected vascular territory (mTICI 3b/3) on initial digital subtraction angiography prior to thrombectomy
- Symptomatic intracerebral hemorrhage (sICH) [ Time Frame: 24 hours post-randomization ]sICH defined as parenchymal hematoma type 2 (PH2) - blood clot occupying >30% of the infarcted territory with substantial mass effect
- Death due to any cause [ Time Frame: 90 days ]
- Modified Rankin Scale (mRS) 5-6 [ Time Frame: 90 days ]Poor functional outcome of death or requirement for fulltime nursing care
- Successful reperfusion at 24 hours [ Time Frame: 24 hours ]Reperfusion (defined as >90% and >50% reduction in perfusion lesion volume)
- Infarct growth [ Time Frame: 24 hours ]Increase in the volume of irreversibly injured brain between pre-treatment and 24 hour imaging
- Recanalization [ Time Frame: 24 hours ]Change in vessel patency between pre-treatment and 24h imaging (CT or MR angiography)
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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
- 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)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04454788
|Contact: Andrew Bivard, PHDfirstname.lastname@example.org|
|Contact: Amy McDonald, BNemail@example.com|
|Australia, New South Wales|
|Liverpool, New South Wales, Australia|
|Contact: Dennis Cordato|
|John Hunter Hospital||Recruiting|
|Newcastle, New South Wales, Australia|
|Contact: Michelle Russell|
|Prince of Wales Hospital||Recruiting|
|Randwick, New South Wales, Australia|
|Contact: Ken Butcher firstname.lastname@example.org|
|Princess Alexandra Hospital||Recruiting|
|Woolloongabba 4102, Queensland, Australia, 4102|
|Contact: Helen Brown|
|Australia, South Australia|
|Royal Adelaide Hospital||Recruiting|
|Adelaide, South Australia, Australia, 5000|
|Contact: Tim Kleinig email@example.com|
|Royal Melbourne Hospital||Recruiting|
|Melbourne, Victoria, Australia, 3050|
|Contact: Amy McDonald|
|Box Hill Hospital||Recruiting|
|Melbourne, Victoria, Australia|
|Contact: Phillip Choi|
|Responsible Party:||Bruce Campbell, Prof, University of Melbourne|
|Other Study ID Numbers:||
|First Posted:||July 2, 2020 Key Record Dates|
|Last Update Posted:||June 22, 2021|
|Last Verified:||June 2021|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
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Molecular Mechanisms of Pharmacological Action