The clomethiazole acute stroke study in ischemic, hemorrhagic, and t-PA treated stroke: Design of a phase III trial in the united states and canada.

Clomethiazole is a drug with sedative properties effective in laboratory studies of brain ischemia. A large European multicenter trial of clomethiazole in acute stroke patients showed no benefit overall, but subgroup analysis indicated that patients with large infarctions may have benefited from treatment. To confirm this preliminary finding, we have designed CLASS-IHT, the Clomethiazole for Acute Stroke Study in Ischemic, Hemorrhagic and TPA Treated Patients, to be conducted in North America. Patients who suffer large cerebral infarctions and present within 12 hours of symptom onset are eligible. Patients will be randomized to receive clomethiazole 68 mg/kg over 24 hours or vehicle, using a dosing scheme based on the pharmacokinetics measured in the first trial. Outcome assessments include stroke scales, the Barthel Index, and lesion volume. An additional study of health economic outcomes is planned. The primary endpoint for CLASS-I will be the Barthel Index 90 days after stroke. A total of 1,200 patients will be randomized to CLASS-I, and in safety-only trials, 200 patients with cerebral hemorrhage will be randomized into CLASS-H and another 100 to 200 patients will be randomized into CLASS-T. The details of the protocols for all three studies are presented.