03859nas a2200685   4500000000100000008004100001653001100042653001100053653000900064653002400073653000900097653001600106653001400122653001300136653001100149653001600160653002200176653001600198653003300214653002700247653001700274653002000291653003000311653002000341653001700361653001500378653002700393653001700420653002200437653001900459653001000478653002400488653002400512653003100536653001700567653001800584653001500602653001600617653002700633100001300660700001400673700001200687700001400699700001500713700001400728700001500742700001700757700001600774700001700790700001600807700003300823700001300856700001900869245009200888250001500980300001100995490000701006520211401013020004603127       2008                            d10aFemale10aHumans10aAged10aDouble-Blind Method10aMale10aMiddle Aged10aPrognosis10aPlacebos10aStroke10aAge Factors10aTreatment Failure10aComorbidity10aDrug Administration Schedule10aMeta-Analysis as Topic10aEpidemiology10aphysiopathology10aAdministration and dosage10aAdverse effects10aDrug therapy10ametabolism10aPrevention and control10aAntioxidants10aBenzenesulfonates10aBrain Ischemia10aBrain10aCerebral Hemorrhage10aCerebral Infarction10aEmergency Medical Services10aEncephalitis10aHyperglycemia10aInjections10aIntravenous10aNeuroprotective Agents1 aDavis S.1 aDiener H.1 aLees K.1 aGrotta J.1 aDavalos A.1 aShuaib A.1 aAshwood T.1 aWasiewski W.1 aAlderfer V.1 aHardemark H.1 aRodichok L.1 aSAINT I and II Investigators1 aLyden P.1 aAnderson Craig00aNXY-059 for the treatment of acute stroke: pooled analysis of the SAINT I and II Trials  a2008/03/29  a1751-80 v393 a<p>
BACKGROUND AND PURPOSE: In animal models of acute ischemic stroke (AIS), the free radical-trapping agent NXY-059 showed promise as a neuroprotectant. SAINT I and II were randomized, placebo-controlled, double-blind trials to investigate the efficacy of NXY-059 in patients with AIS. METHODS: Patients with AIS received an infusion of intravenous NXY-059 or placebo within 6 hours from the onset of stroke symptoms. A pooled individual patient analysis was prespecified to assess the overall efficacy and to examine subgroups. The primary end point was the distribution of disability scores measured on the modified Rankin scale (mRS) at 90 days. Neurologic and activities of daily living scores were investigated as secondary end points. We also evaluated whether treatment with NXY-059 would reduce alteplase-related intracranial hemorrhages. Finally, we evaluated possible predictors of good or poor outcome. RESULTS: An intent-to-treat efficacy analysis was based on 5028 patients. Baseline parameters and prognostic factors were well balanced between treatment groups. The distribution of scores on the mRS was not different in the group treated with NXY-059 (n=2438) compared with the placebo group (n=2456): odds ratio for limiting disability=1.02; 95% CI, 0.92 to 1.13 (P=0.682, Cochran-Mantel-Haenszel test). Comparisons at each level of the mRS confirmed an absence of benefit. There was no evidence of efficacy in prespecified subgroups or from the secondary outcome analyses. Mortality was equal in the 2 groups (16.7% vs 16.5%), and adverse event rates were similar. Among patients treated with alteplase, there was no decrease in rates of symptomatic or asymptomatic hemorrhage associated with NXY-059 treatment versus placebo. Subgroup analyses identified National Institutes of Health Stroke Scale score, age, markers of inflammation, blood glucose, and right-sided infarct as predictors of poor outcome. CONCLUSIONS: NXY-059 is ineffective for treatment of AIS within 6 hours of symptom onset. This is also true for subgroups and the prevention of alteplase-associated hemorrhage.
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