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.
RCT Entities:
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.
Authors: Stephen Davis; Bruce Campbell; Soren Christensen; Henry Ma; Patricia Desmond; Mark Parsons; Christopher Levi; Christopher Bladin; P Alan Barber; Geoffrey Donnan Journal: Transl Stroke Res Date: 2012-04-18 Impact factor: 6.829
Authors: Aaryani Tipirneni-Sajja; Soren Christensen; Matus Straka; Manabu Inoue; Maarten G Lansberg; Michael Mlynash; Roland Bammer; Mark W Parsons; Geoffrey A Donnan; Stephen M Davis; Gregory W Albers Journal: J Cereb Blood Flow Metab Date: 2016-01-01 Impact factor: 6.200
Authors: T Tourdias; P Renou; I Sibon; J Asselineau; L Bracoud; M Dumoulin; F Rouanet; J M Orgogozo; V Dousset Journal: AJNR Am J Neuroradiol Date: 2010-10-21 Impact factor: 3.825
Authors: Hans T H Tu; Bruce C V Campbell; Soren Christensen; Patricia M Desmond; Deidre A De Silva; Mark W Parsons; Leonid Churilov; Maarten G Lansberg; Michael Mlynash; Jean-Marc Olivot; Matus Straka; Roland Bammer; Gregory W Albers; Geoffrey A Donnan; Stephen M Davis Journal: Int J Stroke Date: 2013-03-12 Impact factor: 5.266
Authors: Eckhard Schlemm; Thies Ingwersen; Alina Königsberg; Florent Boutitie; Martin Ebinger; Matthias Endres; Jochen B Fiebach; Jens Fiehler; Ivana Galinovic; Robin Lemmens; Keith W Muir; Norbert Nighoghossian; Salvador Pedraza; Josep Puig; Claus Z Simonsen; Vincent Thijs; Anke Wouters; Christian Gerloff; Götz Thomalla; Bastian Cheng Journal: Nat Commun Date: 2021-05-10 Impact factor: 14.919