Additional Outcomes and Subgroup Analyses of NXY-059 for Acute Ischemic Stroke in the SAINT I Trial

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Abstract
Background and Purpose— NXY-059 is a free radical-trapping neuroprotectant demonstrated to reduce disability from ischemic stroke. We conducted analyses on additional end points and sensitivity analyses to confirm our findings. Methods— We randomized 1722 patients with acute ischemic stroke to a 72-hour infusion of placebo or intravenous NXY-059 within 6 hours of stroke onset. The primary outcome was disability at 90 days, as measured by the modified Rankin Scale (mRS), a 6-point scale ranging from 0 (no residual symptoms) to 5 (bed-bound, requiring constant care). Additional and exploratory analyses included mRS at 7 and 30 days; subgroup interactions with final mRS; assessments of activities of daily living by Barthel index; and National Institutes of Health Stroke Scale (NIHSS) neurological scores at 7 and 90 days. Results— NXY-059 significantly improved the distribution of the mRS disability score compared with placebo at 7, 30, and 90 days (Cochran-Mantel-Haenszel test P =0.002, 0.004, 0.038, respectively; 90-day common odds ratio 1.20; 95% CI, 1.01 to 1.42). The benefit was not attributable to any specific baseline characteristic, stratification variable or subgroup interaction. Neurological scores were improved at 7 days (odds ratio [OR], 1.46; 95% CI, 1.13, 1.89; P =0.003) and the Barthel index was improved at 7 and 30 days (OR, 1.55; 95% CI, 1.22, 1.98; P P =0.02). Conclusions— NXY-059 within 6 hours of acute ischemic stroke significantly reduced disability. Benefit on neurological scores and activities of daily living was detectable early but not significant at 90 days; however, our trial was underpowered to measure effects on the neurological examination. The benefit on disability is not confounded by interactions and is supported by other outcome measures.