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Type: Journal article
Title: Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial
Author: Davis, S.
Donnan, G.
Parsons, M.
Levi, C.
Butcher, K.
Peeters, A.
Barber, P.
Bladin, C.
De Silva, D.
Byrnes, G.
Chalk, J.
Fink, J.
Kimber, T.
Schultz, D.
Hand, P.
Frayne, J.
Hankey, G.
Muir, K.
Gerraty, R.
Tress, B.
et al.
Citation: The Lancet Neurology, 2008; 7(4):299-309
Publisher: Lancet Ltd
Issue Date: 2008
ISSN: 1474-4422
Statement of
Stephen M Davis, Geoffrey A Donnan, Mark W Parsons, Christopher Levi, Kenneth S Butcher, Andre Peeters, P Alan Barber, Christopher Bladin, Deidre A De Silva, Graham Byrnes, Jonathan B Chalk, John N Fink, Thomas E Kimber, David Schultz, Peter J Hand, Judith Frayne, Graeme Hankey, Keith Muir, Richard Gerraty, Brian M Tress, Patricia M Desmond and for the EPITHET investigators
Abstract: Background Whether intravenous tissue plasminogen activator (alteplase) is eff ective beyond 3 h after onset of acute ischaemic stroke is unclear. We aimed to test whether alteplase given 3–6 h after stroke onset promotes reperfusion and attenuates infarct growth in patients who have a mismatch in perfusion-weighted MRI (PWI) and diff usionweighted MRI (DWI). Methods We prospectively and randomly assigned 101 patients to receive alteplase or placebo 3–6 h after onset of ischaemic stroke. PWI and DWI were done before and 3–5 days after therapy, with T2-weighted MRI at around day 90. The primary endpoint was infarct growth between baseline DWI and the day 90 T2 lesion in mismatch patients. Major secondary endpoints were reperfusion, good neurological outcome, and good functional outcome. Patients, caregivers, and investigators were unaware of treatment allocations. Primary analysis was per protocol. This study is registered with, number NCT00238537. Findings We randomly assigned 52 patients to alteplase and 49 patients to placebo. Mean age was 71·6 years, and median score on the National Institutes of Health stroke scale was 13. 85 of 99 (86%) patients had mismatch of PWI and DWI. The geometric mean infarct growth (exponential of the mean log of relative growth) was 1·24 with alteplase and 1·78 with placebo (ratio 0·69, 95% CI 0·38–1·28; Student’s t test p=0·239); the median relative infarct growth was 1·18 with alteplase and 1·79 with placebo (ratio 0·66, 0·36–0·92; Wilcoxon’s test p=0·054). Reperfusion was more common with alteplase than with placebo and was associated with less infarct growth (p=0·001), better neurological outcome (p<0·0001), and better functional outcome (p=0·010) than was no reperfusion. Interpretation Alteplase was non-signifi cantly associated with lower infarct growth and signifi cantly associated with increased reperfusion in patients who had mismatch. Because reperfusion was associated with improved clinical outcomes, phase III trials beyond 3 h after treatment are warranted. Funding National Health and Medical Research Council, Australia; National Stroke Foundation, Australia; Heart Foundation of Australia.
Keywords: EPITHET investigators; Humans; Tissue Plasminogen Activator; Fibrinolytic Agents; Placebos; Echo-Planar Imaging; Treatment Outcome; Thrombolytic Therapy; Severity of Illness Index; Retrospective Studies; Prospective Studies; Double-Blind Method; Drug Evaluation; Time Factors; Aged; Aged, 80 and over; Middle Aged; Female; Male; Stroke
Rights: Copyright © 2008 Elsevier Ltd All rights reserved.
RMID: 0020080454
DOI: 10.1016/S1474-4422(08)70044-9
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