Lubeluzole in acute ischemic stroke treatment - A double-blind study with an 8-hour inclusion window comparing a 10-mg daily dose of lubeluzole with placebo

Background and Purpose-This trial was a double-blind, placebo-controlled, p hase III trial with an 8-hour inclusion window to assess the efficacy and s afety of an intravenous loading dose of 7.5 mg followed by a daily intraven ous dose of 10 mg lubeluzole for 5 days in acute ischemic stroke patients. Methods-A total of 1786 patients were randomized: 901 to lubeluzole and 885 to placebo. Overall, 212 patients (23.5%) from the lubeluzole group and 21 3 (24.1%) from the placebo group discontinued the trial prematurely. In the lubeluzole group 201 patients (22.3%) discontinued because of adverse even ts compared with 193 patients (21.8%) in the placebo group. Results-The primary population for the efficacy analysis comprised the core stroke patients (exclusion of older patients aged >75 years with severe st roke) in the 0- to 6-hour inclusion time window. The primary efficacy param eter was a 3-category functional status (Barthel Index 70 to 100/0 to 70/ve getative, dead) at week 12. In the lubeluzole group 207 patients (47.8%) we re classified as mildly dependent/independent at-week 12, 131 (30.3%) were moderately/severely dependent, and 95 (21.9%) were vegetative/dead, In the placebo group these numbers were 221 (54.4%), 112 (27.6%), and 73 (18.0%), respectively. Logistic regression analysis showed no statistically signific ant difference between the treatment groups (P=0.162). Additionally, for no ne of the secondary efficacy parameters (mortality at week 12, modified Ran kin score, total Barthel score) was a statistically significant difference between the lubeluzole and placebo groups obtained. There were no statistic ally significant differences between the 2 treatments for all treated patie nts, patients included within the 6- to 8-hour window, and patients with se vere strokes aged >75 years. Overall, of all treated patients, 401 (22.5%) died: 203 (22.5%) in the lubeluzole group and 198 (22.4%) with placebo. Of all subjects treated, 853 (95%) on lubeluzole ands 826 (93%) on placebo rep orted an adverse event during their treatment period or within the next 2 d ays after discontinuation of treatment. The most frequently observed advers e events were fever (25.9% lubeluzole; 23.4% placebo), constipation (20.2%; 19.7%), and headache (17.6%; 21.2%), Imbalances were found for atrial fibr illation, (1.8% lubeluzole; 1.1% placebo) and QT prolongation (0.9%; 0.2%). Conclusions-This study failed to show an efficacy of lubeluzole in the trea tment of acute stroke. On the other hand, lubeluzole treatment by the curre nt dosage schedule was not associated with a significant safety problem.