Results in 95 hemorrhagic stroke patients included in CLASS, a controlled trial of clomethiazole versus placebo in acute stroke patients

Background and Purpose-Clomethiazole is a neuroprotective drug that enhance s gamma-aminobutyrate types (GABA,) receptor activity. Its efficacy and saf ety were tested in the CLomethiazole Acute Stroke Study (CLASS). The protoc ol allowed a CT scan to be done after randomization but within 7 days of st roke onset to minimize delays before start of treatment. Ninety-five of the 1360 patients randomized were diagnosed as having intracranial hemorrhage rather than ischemic stroke. Safety results for clomethiazole compared with -placebo in this group are reported. Methods-The study included patients with a clinical diagnosis of acute hemi spheric cerebral infarction. Treatment was a 24-hour intravenous infusion o f 75 mg/kg clomethiazole or placebo. Patients with intracranial hemorrhage discovered on a postrandomization CT were withdrawn from study treatment if treatment was ongoing, and all patients were followed up to 90 days. Results-Ninety-four patients received treatment, 47 in each group. The hemo rrhage was classified as intracerebral in 89 patients (94%). Mortality at 9 0 days was 19.1% in the clomethiazole group and 23.4% in the placebo group, Sedation was the most common adverse event, occurring at a higher incidenc e in clomethiazole-treated patients (clomethiazole 53%, placebo 17%), follo wed by rhinitis and coughing. The incidence and pattern of serious adverse events was similar between the treatment groups. The percentage of patients reaching relative functional independence on the Barthel Index (score grea ter than or equal to 60) at 90 days was 59.6% in the clomethiazole group an d 53.2% in the placebo group. Conclusions-Clomethiazole appears safe to administer to hemorrhagic stroke patients compared with placebo. These results would obviate the need for a CT scan before therapy is initiated in acute stroke. The safety of clomethi azole in hemorrhagic stroke patients will be further evaluated in a prospec tive study that is under way in North America.