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.