BACKGROUND AND PURPOSE: Lubeluzole is a benzothiazole derivative that has shown 
neuroprotective properties in different experimental models. This multicentre, 
double-blind, placebo-controlled trial was conducted to assess the safety and 
efficacy of lubeluzole in patients with an acute ischaemic stroke.
METHODS: Patients who presented with clinical signs and symptoms of acute 
cerebral hemispheric ischaemic stroke were randomised to intravenous therapy 
with placebo (n = 360) or lubeluzole 7.5 mg over 1 h followed by 10 mg/day for 
up to 5 days (n = 365). Treatment was initiated within 6 h of symptom onset. 
Mortality at 12 weeks was the primary end point. Secondary end points included 
neurological status (European Stroke Scale), functional outcome (Barthel Index), 
and disability level (Rankin Scale). The primary and secondary end points were 
all analysed using the protocol-defined Cochran-Mantel-Haenszel's general 
association test. An additional analysis, the logistic regression approach, that 
included risk factors of age, baseline stroke severity and their interactions 
with treatment, was used to analyze outcome measures at 3 months.
RESULTS: In the total ischaemic stroke population, the overall mortality rate at 
3 months was similar for lubeluzole (21.0%) and placebo (21.4%). The logistic 
regression model confirmed the effect of age on mortality risk, but showed that 
this was independent of treatment. Treatment benefit was related to stroke 
severity, as determined by the Clinical Global Impression rating, that is a 
pronounced clinically significant reduction in mortality was noted in the 
lubeluzole-treated patients for whom stroke severity was mild to moderate, but 
not in those for whom it was severe. This was found on the basis of a post hoc 
analysis not specified in the hypothesis. Lubeluzole did not increase morbidity 
among stroke survivors, as measured by the European Stroke Scale, Barthel Index 
and Rankin Scale. No safety concerns were seen with lubeluzole treatment.
CONCLUSIONS: In the overall study population, treatment with intravenous 
lubeluzole within 6 h of the onset of ischaemic stroke did not affect mortality 
or clinical outcome. Among patients with mild to moderate ischaemic stroke, 
lubeluzole decreased mortality without increasing morbidity.