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Previous Volume 354:588-600 February 9, 2006 Number 6 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Perspective by del Zoppo, G. J. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background NXY-059 is a free-radical–trapping agent that is neuroprotective in animal models of stroke. We tested whether it would reduce disability in humans after acute ischemic stroke.

Methods We conducted a randomized, double-blind, placebo-controlled trial involving 1722 patients with acute ischemic stroke who were randomly assigned to receive a 72-hour infusion of placebo or intravenous NXY-059 within 6 hours after the onset of the stroke. The primary outcome was disability at 90 days, as measured according to scores on the modified Rankin scale for disability (range, 0 to 5, with 0 indicating no residual symptoms and 5 indicating bedbound, requiring constant care).

Results Among the 1699 subjects included in the efficacy analysis, NXY-059 significantly improved the overall distribution of scores on the modified Rankin scale, as compared with placebo (P=0.038 by the Cochran–Mantel–Haenszel test). The common odds ratio for improvement across all categories of the scale was 1.20 (95 percent confidence interval, 1.01 to 1.42). Mortality and rates of serious and nonserious adverse events were each similar in the two groups. NXY-059 did not improve neurologic functioning as measured according to the National Institutes of Health Stroke Scale (NIHSS): the difference between the two groups in the change from baseline scores was 0.1 point (95 percent confidence interval, –1.4 to 1.1; P=0.86). Likewise, no improvement was observed according to the Barthel index (P=0.14). In a post hoc analysis of patients who also received alteplase, NXY-059 was associated with a lower incidence of any hemorrhagic transformation (P=0.001) and symptomatic intracranial hemorrhage (P=0.036).

Conclusions The administration of NXY-059 within six hours after the onset of acute ischemic stroke significantly improved the primary outcome (reduced disability at 90 days), but it did not significantly improve other outcome measures, including neurologic functioning as measured by the NIHSS score. Additional research is needed to confirm whether NXY-059 is beneficial in ischemic stroke. (ClinicalTrials.gov number, NCT00119626 [ClinicalTrials.gov] .)

Source Information

From the Acute Stroke Unit and Cerebrovascular Clinic, University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow (K.R.L.); the Department of Neurosciences, University of California, San Diego, La Jolla (J.A.Z.); AstraZeneca Research and Development Södertälje, Medical Neuroscience, Södertälje, Sweden (T.A., H.-G.H.); the Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain (A.D.); the Department of Neurology, Royal Melbourne Hospital, University of Melbourne, Parkville, Melbourne, Victoria, Australia (S.M.D.); the Department of Neurology, University Duisburg-Essen, Essen, Germany (H.-C.D.); the Department of Neurology, University of Texas–Houston Medical School, Houston (J.G.); University of California, San Diego, Stroke Center, La Jolla (P.L.); the Department of Neurology, University of Alberta, Edmonton, Alta., Canada (A.S.); and AstraZeneca, Clinical Research, Emerging Products, Wilmington, Del. (W.W.W.).

Address reprint requests to Dr. Lees at the Acute Stroke Unit and Cerebrovascular Clinic, University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, 44 Church St., Glasgow G11 6NT, United Kingdom, or at k.r.lees{at}clinmed.gla.ac.uk.

Full Text of this Article

Related Letters:

NXY-059 for Acute Ischemic Stroke
Serebruany V., Koziol J. A., Lees K. R., Lyden P., Shuaib A.
Extract | Full Text | PDF  
N Engl J Med 2006; 354:2075-2076, May 11, 2006. Correspondence

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