BACKGROUND AND PURPOSE: We aimed to assess the safety and efficacy of lubeluzole 
in patients with a clinical diagnosis of acute (< 6 hours) ischemic stroke in 
the carotid artery territory.
METHODS: A randomized, double-blind, placebo-controlled multicenter trial was 
conducted in 232 patients. Because treatment was administered within 6 hours and 
a CT scan was not mandatory before the start of treatment, 39 patients with 
either an intracerebral hemorrhage or ischemic stroke in the vertebrobasilar 
circulation were excluded from the primary efficacy analysis as prespecified in 
the protocol. Of the 193 patients with acute ischemic stroke in the carotid 
artery territory (target population), 61 received placebo, 66 lubeluzole 7.5 mg 
over 1 hour followed by 10 mg/d for 5 days, and 66 lubeluzole 15 mg over 1 hour 
followed by 20 mg/d for 5 days.
RESULTS: The trial, initially aimed at a patient inclusion of 270, was 
terminated prematurely according to the advice of the Safety Committee because 
of an imbalance in mortality between the treatment groups. Mortality rates at 
the final follow-up of 28 days for placebo, lubeluzole 10 mg/d, and lubeluzole 
20 mg/d were, respectively, 18%, 6%, and 35% in the target population, results 
that were confirmed in the intent-to-treat population. Multivariate logistic 
regression analysis showed that the lower mortality in the lubeluzole 10 mg/d 
group was significantly in favor of the 10 mg/d treatment (P = .019). The higher 
mortality rate in the 20 mg/d group could be explained, at least in part, by an 
imbalance at randomization that led to a higher number of patients in that group 
with severe ischemic stroke. A total of 26 of 66 patients (39%) who received 
lubeluzole 10 mg/d had a score on the Barthel Index of > 70 at day 28, 
indicating no or mild disability, compared with 21 of 61 (34%) in the placebo 
group and 19 of 66 (29%) in the lubeluzole 20 mg/d group (P = NS).
CONCLUSIONS: In patients with acute ischemic stroke, the dosage regimen of 7.5 
mg over 1 hour followed by 10 mg/d of intravenous lubeluzole is safe and 
statistically significantly reduced mortality. Further clinical trials in a 
larger number of patients are ongoing to confirm efficacy.