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.