The clomethiazole acute stroke study (CLASS): Efficacy results in 545 patients classified as total anterior circulation syndrome (TACS)

Abstract

The CLASS study showed no significant difference between treatment groups for the neuroprotectant clomethiazole compared with placebo. However, a beneficial effect of the drug was seen in patients with total anterior circulation syndrome (TACS). These are patients with clinical symptoms suggesting a large stroke. Full results of this subgroup analysis are reported. Patients were classified before randomization using clinical symptoms into the stroke syndromes TACS, partial anterior circulation syndrome, and lacunar syndrome. Subgroup analyses of stroke syndromes were performed post hoc after detecting a treatment by severity interaction. The primary efficacy variable was relative functional independence defined as the proportion of patients scoring > or =60 on the Barthel Index at 90 days. TACS patients (n=546, 40% of all CLASS patients) were more severe at baseline on the 58 point Scandinavian Stroke Scale compared with non-TACS patients (median difference 10 points, mean difference 10.9 points, SE=0.6). Outcome for TACS patients treated with placebo was poor, with only 29.8% reaching relative functional independence. This was increased to 40.8% in the clomethiazole group, a 37% relative benefit, which is clinically significant (odds ratio=1.62, 95% CI 1.13-2.31, nominal P=.008). There was little or no difference in the outcome of non-TACS patients treated with clomethiazole compared with placebo. The treatment effect in TACS patients was quite consistent across participating countries and the 3 parts of the study defined by the 2 interim analyses. The treatment effect seen in patients with clinical symptoms suggesting a large stroke (TACS) is biologically plausible but requires confirmation in a prospective study which is ongoing.