The clomethiazole acute stroke study (CLASS): Safety results in 1,356 patients with acute hemispheric stroke

The Clomethiazole Acute Stroke Study (CLASS) showed no difference in outcome between patients treated with clomethiazole or placebo for all patients treated, but a beneficial effect in patients classified as a total anterior circulation syndrome (TACS). These are patients with clinical symptoms of a large stroke. Safety and tolerability data are reported here with emphasis on the safety of treating stroke patients with a sedative drug. In total, 1,356 patients were eligible for safety analysis. Mortality at 90 days was equal between the treatment groups (clomethiazole, 19.5%; placebo, 19.7%). Clomethiazole was generally well-tolerated. The most common adverse event was sedation (clomethiazole, 53%; placebo, 10%). Clomethiazole also produced some respiratory adverse events (e.g., rhinitis and increased sputum). Serious adverse events associated with sedation were more commonly reported in the clomethiazole group during treatment. However, the incidence was low. There was no difference in the incidence of serious adverse events between the treatment groups for pulmonary conditions, cardiovascular conditions, or other conditions. Clomethiazole produced a small decrease in blood pressure, but this was not associated with a worse outcome. Safety and tolerability in TACS patients was similar to that for all patients treated with the exception that these patients were more sensitive to the sedative effects of the drug. Despite this, mortality was slightly lower, and functional outcome was better in clomethiazole-treated TACS patients compared with placebo. In conclusion, clomethiazole was generally well-tolerated. The sedation observed did not increase the risk for complications, such as pulmonary serious adverse events or affect the outcome in a negative way. Clomethiazole appeared to be safe to use in stroke patients in general and in patients with a large stroke. The efficacy and safety in large strokes will be studied further in a new study, which is ongoing.