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.