(Stroke. 1999;30:21-28.)
© 1999 American Heart Association, Inc.
Original Contributions |
Clomethiazole Acute Stroke Study (CLASS)
Results of a Randomized, Controlled Trial of Clomethiazole Versus Placebo in 1360 Acute Stroke Patients
From the Stroke Research Unit, Department of Neurology, Karolinska Hospital, Stockholm, Sweden (N.G.W.); Epsom General Hospital, Epsom, United Kingdom (K.W.R.); Centre Hospitalier, Department de Neurologie Maubeuge, Maubeuge, France (T.R.); Department of Neurology De Wever Ziekenhuis, Heerlen, the Netherlands (C.L.F.); Department of Neurology, Ignatius Ziekenhuis, Breda, the Netherlands (P.M.M. v E.); and Astra Arcus AB, Södertälje, Sweden (T.A., L.C.).
Correspondence to N.G. Wahlgren, MD, PhD, The Stroke Research Unit, Department of Neurology, Karolinska Hospital, S-171 76 Stockholm, Sweden. E-mail nilsgw{at}neuro.ks.se
Background and Purpose—The efficacy and safety of the neuroprotective drug clomethiazole was tested in a double blind placebo controlled trial in patients with a clinical diagnosis of acute hemispheric stroke.
Methods—Patients with symptom onset of 
12 hours before the
start of treatment were included in the study. Clomethiazole (75 mg/kg)
or placebo was given as an intravenous infusion over a
24-hour period. Patients were followed up for 90 days. The primary
efficacy variable was the proportion of patients reaching relative
functional independence (
60 points on the Barthel Index) at 90
days.
Results—A total of 1360 patients were included. In the main efficacy analysis (n=1353), 56.1% of patients taking clomethiazole and 54.8% of placebo patients reached relative functional independence. The difference was not statistically significant. An analysis of the effect of time since onset of symptoms showed no difference between the treatment groups. Clomethiazole was generally well tolerated and appeared safe in the population studied. Sedation was the most common adverse event, leading to treatment withdrawal that occurred in 15.6% of clomethiazole-treated patients compared with 4.2% of placebo-treated patients. In a subgroup classified before randomization as having total anterior circulation syndrome (TACS) (n=545, or 40% of all randomized patients), the percentage of those reaching relative functional independence was 40.8% on clomethiazole and 29.8% on placebo, a difference of approximately 11 percentage units. TACS patients have clinical symptoms suggesting a "large" stroke.
Conclusions—Clomethiazole had no adverse or beneficial effect on long-term outcome for all patients but produced sedation. The hypothesis that clomethiazole is effective in patients with large strokes will be tested in a further study.
Key Words: cerebral ischemia • clinical trials • clomethiazole • efficacy • neuroprotection
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