BACKGROUND AND PURPOSE: UK-279,276 (neutrophil inhibitory factor) reduced @entity1188 volume in a @entity35 middle cerebral @entity432 reperfusion model. ASTIN (Acute @entity64 Therapy by Inhibition of Neutrophils) was an adaptive phase 2 dose-response-finding, proof-of-concept study to establish whether UK-279,276 improves recovery in acute @entity385 . The prime objective was to determine the dose that gave a clinically relevant effect in @entity1 . METHODS: A Bayesian sequential design with real-time efficacy data capture and continuous reassessment of the dose response allowed double-blind, randomized, adaptive allocation to 1 of 15 doses (dose range, 10 to 120 mg) or placebo and early termination for efficacy or futility. The primary end point was change from baseline to day 90 on the Scandinavian @entity64 Scale (DeltaSSS), adjusted for baseline SSS, aiming for a 3-point additional mean recovery above placebo. RESULTS: Nine hundred sixty-six acute @entity64 @entity1 (887 ischemic, 204 cotreated with intravenous tissue plasminogen activator; mean baseline SSS score, 28; range, 10 to 40) were treated within 6 hours of symptom onset. Mean DeltaSSS was approximately +17 points of improvement on SSS for the overall evaluable population. There was no treatment effect for UK-279,276 (posterior probability of futility, 0.89). The trial was stopped early for futility. Post hoc analysis indicated a mean 1.6-point additional improvement on DeltaSSS in the tissue plasminogen activator-treated subset (credible interval=0.5, 2.6). UK-279,276 was generally well tolerated, with no increased incidence of @entity281 . CONCLUSIONS: UK-279,276 did not improve recovery in acute @entity385 @entity1 but was devoid of serious side effects. The adaptive design facilitated early termination for futility.

Acute XXXX Therapy by Inhibition of Neutrophils (ASTIN): an adaptive dose-response study of UK-279,276 in acute @entity385 .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity64 :: ('MESH:D020521', 'Disease') :: ['stroke', 'Stroke'] @entity281 :: ('MESH:D007239', 'Disease') :: ['infections'] @entity1188 :: ('MESH:D007238', 'Disease') :: ['infarct'] @entity432 :: ('MESH:D001157', 'Disease') :: ['artery occlusion'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity385 :: ('MESH:D002544', 'Disease') :: ['ischemic stroke']
@entity64 :: (MESH:D020521,Disease) :: ['Stroke']
