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Previous Volume 357:562-571 August 9, 2007 Number 6 Next

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ABSTRACT

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 was 0.92 (95% CI, 0.80 to 1.06). There was no evidence of efficacy for any of the secondary end points. Among patients treated with alteplase, there was no difference between the NXY-059 group and the placebo group in the frequency of symptomatic or asymptomatic hemorrhage.

Conclusions NXY-059 is ineffective for the treatment of acute ischemic stroke within 6 hours after the onset of symptoms. (ClinicalTrials.gov number, NCT00061022 [ClinicalTrials.gov] .)

Source Information

From the Division of Neurology, University of Alberta, Edmonton, Canada (A.S.); the Acute Stroke Unit and Cerebrovascular Clinic, University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow, United Kingdom (K.R.L.); the University of California San Diego Stroke Center, San Diego (P.L.); the Department of Neurology, University of Texas–Houston Medical School, Houston (J.G.); 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, Australia (S.M.D.); the Department of Neurology, University Duisburg–Essen, Essen, Germany (H.-C.D.); AstraZeneca R&D Södertälje, Medical Neuroscience, Södertälje, Sweden (T.A.); and AstraZeneca, Wilmington, DE (W.W.W., U.E.).

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.

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Related Letters:

NXY-059 for the Treatment of Stroke
Savitz S. I., Fisher M., Lyden P., Lees K. R., Shuaib A.
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N Engl J Med 2007; 357:2198-2199, Nov 22, 2007. Correspondence

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