Clinical trial NCT02388061: Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke
Official title: Extending the Time for Thrombolysis in Emergency Neurological Deficits - Intra-Arterial Using Intravenous Tenecteplase
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ischemic Stroke
Lead sponsor: Neuroscience Trials Australia
Sponsor class: OTHER
Collaborators: name: The Florey Institute of Neuroscience and Mental Health
First posted: 2015-03-13
Enrollment: 202
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients presenting to the emergency department with acute ischemic stroke, who are are eligible for standard intravenous tPA therapy within 4.5 hours of stroke onset will be assessed for major vessel occlusion to determine their eligibility for randomization into the trial. If the patient gives informed consent they will be randomised 50:50 using central computerised allocation to intravenous alteplase or tenecteplase before all participants undergo intra-arterial clot retrieval. The trial is prospective, randomised, open-label, blinded endpoint (PROBE) design.


Eligibility criteria: Inclusion Criteria:

1. Patients presenting with acute ischemic stroke eligible using standard criteria to receive IV thrombolysis within 4.5 hours of stroke onset
2. Patient's age is ≥18 years
3. Intra-arterial clot retrieval treatment can commence (arterial puncture) within 6 hours of stroke onset.
4. Arterial occlusion on CTA or MRA of the ICA, M1, M2 or basilar artery.

Exclusion Criteria:

1. Intracranial hemorrhage (ICH) identified by CT or MRI
2. Rapidly improving symptoms at the discretion of the investigator
3. Pre-stroke mRS score of ≥ 4 (indicating previous disability)
4. Hypodensity in \>1/3 MCA territory or equivalent proportion of basilar artery territory on non-contrast CT
5. Contra indication to imaging with contrast agents
6. Any terminal illness such that patient would not be expected to survive more than 1 year
7. 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.
8. Pregnant women

Primary outcomes:
measure: Proportion of patients with substantial angiographic reperfusion (mTICI) score of 2b/3 (restoration of blood flow to >50% of the affected arterial territory) or absence of retrievable thrombus at initial angiogram.
timeFrame: Initial angiogram (day 0)
Secondary outcomes:
measure: Proportion of patients with ≥8 point reduction in NIHSS or reaching 0-1 at 3 days (favourable clinical response) adjusted for baseline NIHSS and age.
timeFrame: Initial angiogram (day 0)
measure: Modified Rankin Scale (mRS) at 3 months
timeFrame: 3 months post stroke
measure: mRS 0-1 or no change from baseline at 3 months
timeFrame: 3 months post stroke
measure: mRS 0-2 or no change from baseline at 3 months
timeFrame: 3 months post stroke
measure: Symptomatic intracranial hemorrhage (SICH)
timeFrame: within 36 hours post treatment
measure: Death due to any cause
timeFrame: Up to 3 months post stroke
measure: Proportion of patients with angiographic reperfusion adjusted for hyperdense clot length on non-contrast CT and time from thrombolysis to initial angiogram
timeFrame: Up to 24 hours post treatment
Other outcomes:
Locations:
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Gosford
country: Australia
facility: Gosford Hospital
state: New South Wales
city: Newcastle
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Brisbane & Women's Hospital
state: Queensland
city: Gold Coast
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Elizabeth Vale
country: Australia
facility: Lyell McEwin Hospital
state: South Australia
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: St Albans
country: Australia
facility: Western Heath
state: Victoria
city: Grafton
country: New Zealand
facility: Auckland Hospital
state: Auckland
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
Study officials:
References:
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citation: Ng FC, Churilov L, Yassi N, Kleinig TJ, Thijs V, Wu T, Shah D, Dewey H, Sharma G, Desmond P, Yan B, Parsons M, Donnan G, Davis S, Mitchell P, Campbell B. Prevalence and Significance of Impaired Microvascular Tissue Reperfusion Despite Macrovascular Angiographic Reperfusion (No-Reflow). Neurology. 2022 Feb 22;98(8):e790-e801. doi: 10.1212/WNL.0000000000013210. Epub 2021 Dec 14.
citation: Alemseged F, Ng FC, Williams C, Puetz V, Boulouis G, Kleinig TJ, Rocco A, Wu TY, Shah D, Arba F, Kaiser D, Di Giuliano F, Morotti A, Sallustio F, Dewey HM, Bailey P, O'Brien B, Sharma G, Bush S, Dowling R, Diomedi M, Churilov L, Yan B, Parsons MW, Davis SM, Mitchell PJ, Yassi N, Campbell BCV; BATMAN study group and EXTEND IA TNK study group. Tenecteplase vs Alteplase Before Endovascular Therapy in Basilar Artery Occlusion. Neurology. 2021 Mar 2;96(9):e1272-e1277. doi: 10.1212/WNL.0000000000011520. Epub 2021 Jan 6.
citation: Gao L, Moodie M, Mitchell PJ, Churilov L, Kleinig TJ, Yassi N, Yan B, Parsons MW, Donnan GA, Davis SM, Campbell BCV; EXTEND-IA TNK Investigators. Cost-Effectiveness of Tenecteplase Before Thrombectomy for Ischemic Stroke. Stroke. 2020 Dec;51(12):3681-3689. doi: 10.1161/STROKEAHA.120.029666. Epub 2020 Oct 7.
citation: Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, Yan B, Bush SJ, Dewey HM, Thijs V, Scroop R, Simpson M, Brooks M, Asadi H, Wu TY, Shah DG, Wijeratne T, Ang T, Miteff F, Levi CR, Rodrigues E, Zhao H, Salvaris P, Garcia-Esperon C, Bailey P, Rice H, de Villiers L, Brown H, Redmond K, Leggett D, Fink JN, Collecutt W, Wong AA, Muller C, Coulthard A, Mitchell K, Clouston J, Mahady K, Field D, Ma H, Phan TG, Chong W, Chandra RV, Slater LA, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Bladin CF, Sharma G, Desmond PM, Parsons MW, Donnan GA, Davis SM; EXTEND-IA TNK Investigators. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018 Apr 26;378(17):1573-1582. doi: 10.1056/NEJMoa1716405.
citation: Campbell BC, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Yan B, Dowling RJ, Bush SJ, Dewey HM, Thijs V, Simpson M, Brooks M, Asadi H, Wu TY, Shah DG, Wijeratne T, Ang T, Miteff F, Levi C, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Bailey P, Rice H, de Villiers L, Scroop R, Collecutt W, Wong AA, Coulthard A, Barber PA, McGuinness B, Field D, Ma H, Chong W, Chandra RV, Bladin CF, Brown H, Redmond K, Leggett D, Cloud G, Madan A, Mahant N, O'Brien B, Worthington J, Parker G, Desmond PM, Parsons MW, Donnan GA, Davis SM; EXTEND-IA TNK Investigators. Tenecteplase versus alteplase before endovascular thrombectomy (EXTEND-IA TNK): A multicenter, randomized, controlled study. Int J Stroke. 2018 Apr;13(3):328-334. doi: 10.1177/1747493017733935. Epub 2017 Sep 27.