Effectively bridging the preclinical/clinical gap: the results of the ASTIN trial.

To the Editor: Recently, the results of the Acute Stroke Therapy by Inhibition of Neutrophils (ASTIN) were published.1 In this trial, 966 patients presenting within 6 hours of acute stroke received varying doses of either placebo or UK-279,276, a CD11b/CD18 inhibitor. Additionally, a subgroup of 204 patients was co-administered tissue plasminogen activator (tPA) when clinically appropriate. The trial was stopped early when interim analysis demonstrated futility in achieving the primary end point of increased functional improvement from the patient’s baseline as measured by the Scandinavian Stroke Scale (SSS) at 90 days. Post hoc analysis found that patients co-administered tPA and UK-279,276 exhibited a mean improvement of 1.6 points on the SSS, but this study was neither designed nor powered to achieve statistical significance in this group. While the study utilized a novel approach to clinical trial design and management, there are limitations in the design of this study that, while stated by the authors, merit additional attention. The first of these is the study’s diminished emphasis on UK-279,276 as an adjuvant for …