NXY-059 for the Treatment of Acute Ischemic Stroke

作者：Ashfaq Shuaib, Kennedy R. Lees, Patrick D. Lyden, James C. Grotta, Antonio Dávalos, Stephen M. Davis, Hans‐Christoph Diener, Tim Ashwood, Warren W. Wasiewski, Ugochi Emeribe · 发表于：New England Journal of Medicine · 年份：2007 · DOI：10.1056/nejmoa070240 · 被引用次数：729 · 研究领域：Acute Ischemic Stroke Management、S100 Proteins and Annexins、Neuroinflammation and Neurodegeneration Mechanisms

BACKGROUND: The free-radical-trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke-Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke. We sought confirmation of efficacy in a second, larger trial. METHODS: We enrolled 3306 patients with acute ischemic stroke in a randomized, double-blind trial to receive a 72-hour infusion of intravenous NXY-059 or placebo within 6 hours after the onset of stroke symptoms. Our primary end point was the distribution of disability scores on the modified Rankin scale at 90 days. We examined scores on neurologic and activities-of-daily-living scales as secondary end points. We also tested the hypothesis that NXY-059 would reduce alteplase-related intracranial hemorrhages. RESULTS: The efficacy analysis was based on 3195 patients. Prognostic factors were well balanced between the treatment groups. Mortality was equal in the two groups, and adverse-event rates were similar. The distribution of scores on the modified Rankin scale did not differ between the group treated with NXY-059 (1588 patients) and the placebo group (1607 patients; P=0.33 by the Cochran-Mantel-Haenszel test; odds ratio for limiting disability, 0.94; 95% confidence interval [CI], 0.83 to 1.06). Analysis of categorized scores on the modified Rankin scale confirmed the lack of benefit: the odds ratio for trichotomization into modified Rankin scale scores of 0 to 1 versus 2 to 3 versus 4 to 6 wa...