Clomethiazole Acute Stroke Study (CLASS) - Results of a randomized, controlled trial of clomethiazole versus placebo in 1360 acute stroke patients

Background and Purpose-The efficacy and safety of the neuroprotective drug clomethiazole was tested in a double blind placebo controlled trial in pati ents with a clinical diagnosis of acute hemispheric stroke. Methods-Patients with symptom onset of less than or equal to 12 hours befor e the start of treatment were included in the study. Clomethiazole (75 mg/k g) or placebo was given as an intravenous infusion over a 24-hour period. P atients were followed up for 90 days. The primary efficacy variable was the proportion of patients reaching relative functional independence (greater than or equal to 60 points on the Barthel Index) at 90 days. Results-A total of 1360 patients were included. In the main efficacy analys is (n = 1353), 56.1% of patients taking clomethiazole and 54.8% of placebo patients reached relative functional independence. The difference was not s tatistically significant. An analysis of the effect of time since onset of symptoms showed no difference between the treatment groups. Clomethiazole w as generally well tolerated and appeared safe in the population studied. Se dation was the most common adverse event, leading to treatment withdrawal t hat occurred in 15.6% of clomethiazole-treated patients compared with 4.2% of placebo-treated patients. In a subgroup classified before randomization as having total anterior circulation syndrome (TACS) (n = 545, or 40% of al l randomized patients), the percentage of those reaching relative functiona l independence was 40.8% on clomethiazole and 29.8% on placebo, a differenc e of approximately 11 percentage units. TACS patients have clinical symptom s suggesting a "large" stroke. Conclusions-Clomethiazole had no adverse or beneficial effect on long-term outcome for all patients but produced sedation. The hypothesis that clometh iazole is effective in patients with large strokes will be tested in a furt her study.