NXY-059 for the treatment of acute ischemic stroke.
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].)
Shuaib
Ashfaq
A
Division of Neurology, University of Alberta, Edmonton, Canada.
Lees
Kennedy R
KR
Lyden
Patrick
P
Grotta
James
J
Davalos
Antonio
A
Davis
Stephen M
SM
Diener
Hans-Christoph
HC
Ashwood
Tim
T
Wasiewski
Warren W
WW
Emeribe
Ugochi
U
D000208:Acute Disease; D000368:Aged; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy*; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D016017:Odds Ratio; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality; D013997:Time Factors; D017211:Treatment Failure
D001557:Benzenesulfonates; D002317:Cardiovascular Agents; C120851:disufenton sodium