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(Stroke. 2000;31:82.)
© 2000 American Heart Association, Inc.

Original Contributions

Results in 95 Hemorrhagic Stroke Patients Included in CLASS, a Controlled Trial of Clomethiazole Versus Placebo in Acute Stroke Patients

N. G. Wahlgren, MD, PhD; E. Díez-Tejedor, MD, PhD; J. Teitelbaum, MD, FRCP(C); A. Arboix, MD; D. Leys, MD; T. Ashwood, PhD; E. Grossman, MD for the CLASS (CLomethiazole Acute Stroke Study) Study Group

From the Stroke Research Unit, Department of Neurology, Karolinska Hospital, Stockholm, Sweden (N.G.W.); Stroke Unit, Department of Neurology, University Hospital La Paz, Universidad Autónoma de Madrid, Spain (E.D.-T.); Hopital Maisonneuve Rosemont, Montreal, Canada (J.T.); Quinta de Salud la Alianza, Servicio de Neurologia, Barcelona, Spain (A.A.); Service de Neurologie Vasculaire, Hôpital Roger Salengro, Lille, France (D.L.); and AstraZeneca, Södertälje, Sweden (T.A., E.G.).

Correspondence to N.G. Wahlgren, MD, The Stroke Research Unit, Department of Neurology, Karolinska Hospital, S-171 76 Stockholm, Sweden. E-mail nilsgw{at}neuro.ks.se

Background and Purpose—Clomethiazole is a neuroprotective drug that enhances -aminobutyrate type A (GABA_A) receptor activity. Its efficacy and safety were tested in the CLomethiazole Acute Stroke Study (CLASS). The protocol allowed a CT scan to be done after randomization but within 7 days of stroke 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 hemispheric cerebral infarction. Treatment was a 24-hour intravenous infusion of 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 Patients with intracranial hemorrhage discovered on a postrandomization CT were withdrawn from study treatment if treatment was ongoing, and all patients were followed up to 90 days.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 hemorrhage was classified as intracerebral in 89 patients (94%). Mortality at 90 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 incidence in clomethiazole-treated patients (clomethiazole 53%, placebo 17%), followed 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 60) at 90 days was 59.6% in the clomethiazole group and 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 clomethiazole in hemorrhagic stroke patients will be further evaluated in a prospective study that is under way in North America.

Key Words: cerebral ischemia • clinical trials • clomethiazole • hemorrhage • neuroprotection

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