Expediting MRI-based proof-of-concept stroke trials using an earlier imaging end point

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dc.contributor.author Ebinger, M en
dc.contributor.author Christensen, S en
dc.contributor.author DeSilva, DA en
dc.contributor.author Parsons, MW en
dc.contributor.author Levi, CR en
dc.contributor.author Butcher, KS en
dc.contributor.author Bladin, CF en
dc.contributor.author Barber, Peter en
dc.contributor.author Donnan, GA en
dc.contributor.author Davis, SM en
dc.date.accessioned 2012-03-12T02:25:42Z en
dc.date.issued 2009 en
dc.identifier.citation Stroke 40(4):1353-1358 Apr 2009 en
dc.identifier.issn 0039-2499 en
dc.identifier.uri http://hdl.handle.net/2292/13893 en
dc.description.abstract Background and Purpose— Before Phase III trials of acute stroke therapies, proof-of-concept MRI trials are increasingly used to gauge the likelihood of success. Given that animal models use infarct volume as the end point, Phase II trials have aimed to translate the findings using infarct growth. These trials could be expedited if subacute diffusion-weighted imaging lesion volume replaced late T2-weighted lesion volume as the primary end point. Methods— In the Echoplanar Imaging Thrombolytic Evaluation Trial, patients with acute ischemic stroke presenting within 3 to 6 hours were randomized to tissue plasminogen activator or placebo. We assessed correlations between acute (Day 1), subacute (Day 3 to 5) as well as late (Day 90) lesion volumes and clinical outcome (National Institutes of Health Stroke Scale). We compared lesion growth between placebo- and tissue plasminogen activator-treated patients. Results— All 3 scans were performed in 72 of 101 patients (32 tissue plasminogen activator, 40 placebo). Median time to subacute imaging was 3 days (interquartile range, 2 to 4) and 90 days (interquartile range, 90 to 95) for the late scan. Increase in lesion volume from acute to subacute scans was smaller in the tissue plasminogen activator group compared with the placebo group (6.77 mL; interquartile range, 2.30 to 49.10; versus 30.00 mL; interquartile range, 7.19 to 85.93; P=0.03). Subsequent shrinkage did not reveal significant treatment effects. Correlation coefficient between acute and late lesion volumes was 0.81 (P<0.01). Subacute and late lesion volumes were strongly correlated (rho=0.94, P<0.01). Correlation coefficient for acute, subacute, and late lesion volume and late National Institutes of Health Stroke Scale score was 0.64 (P<0.01), 0.81 (P<0.01), and 0.77 (P<0.01), respectively. Conclusions— These findings suggest that subacute imaging at Day 3 after thrombolysis is an appropriate imaging end point for proof-of-concept MRI-based stroke treatment trials and can replace later MRI measurements. en
dc.publisher American Heart Association en
dc.relation.ispartofseries Stroke en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0039-2499/ en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title Expediting MRI-based proof-of-concept stroke trials using an earlier imaging end point en
dc.type Journal Article en
dc.identifier.doi 10.1161/STROKEAHA.108.532622 en
pubs.issue 4 en
pubs.begin-page 1353 en
pubs.volume 40 en
dc.rights.holder Copyright: American Heart Association en
dc.identifier.pmid 19246703 en
pubs.end-page 1358 en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Article en
pubs.elements-id 83676 en
pubs.org-id Medical and Health Sciences en
pubs.org-id School of Medicine en
pubs.org-id Medicine Department en
pubs.record-created-at-source-date 2010-09-01 en
pubs.dimensions-id 19246703 en

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