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(Stroke. 2002;33:122.)
© 2002 American Heart Association, Inc.

Original Contributions

Clomethiazole Acute Stroke Study in Ischemic Stroke (CLASS-I)

Final Results

P. Lyden, MD; A. Shuaib, MD; K. Ng, MD; K. Levin, MD; R.P. Atkinson, MD; A. Rajput, MD; L. Wechsler, MD; T. Ashwood, PhD; L. Claesson, MS; T. Odergren, MD E. Salazar-Grueso, MD on behalf of the CLASS-I/H/T Investigators

From the Departments of Neurosciences, UCSD School of Medicine, and Neurology, Veterans Administration Medical Center (P.L.), San Diego, Calif; Department of Neurology (A.S.), University of Alberta, Edmonton, Alberta; Ocala Medical Center (K.N.), Ocala, Fla; Neurology Group of Bergen County (K.L.), Ridgewood, NJ; Mercy General Hospital (R.A.), Sacramento, Calif; Department of Neurology, Royal University Hospital (A.R.), Saskatoon, Saskatchewan; University of Pittsburgh Medical Center Stroke Center (L.W.), Pittsburgh, Pa; AstraZeneca (T.A., L.C., T.O.), Södertälje, Sweden, and AstraZeneca LP (E.S-G.), Wilmington, Del.

Correspondence to Dr Patrick Lyden, OPC Third Floor, Suite 3, 200 W Arbor Dr, San Diego, CA 92103–8466. E-mail plyden{at}ucsd.edu

Background and Purpose— A previous trial (the Clomethiazole Acute Stroke Study) generated the hypothesis that clomethiazole is effective in patients with a major ischemic stroke (total anterior circulation syndrome), and this was tested in the present study.

Methods— A total of 1198 patients with major ischemic stroke and a combination of limb weakness, higher cortical dysfunction, and visual field deficits were randomly assigned to clomethiazole (68 mg/kg IV over 24 hours) or placebo. The study drug was initiated within 12 hours of symptom onset. Functional outcome and neurological recovery were assessed at days 7, 30, and 90, with the proportion of patients with a Barthel Index 60 at last follow-up as the primary outcome measure.

Results— The patients were randomly assigned equally, and the two treatment groups were well matched for baseline characteristics, including stroke severity (mean National Institutes of Health Stroke Scale score 16.9±5.2). Ninety-six percent were classified as total anterior circulation syndrome. The proportion of patients reaching a Barthel Index score of 60 was 42% in the clomethiazole-treated group and 46% in the placebo-treated group (odds ratio, 0.81; 95% CI, 0.62 to 1.05; P=0.11). There was no evidence of efficacy on any secondary outcome variables (modified Rankin Score, National Institutes of Health Stroke Scale, Scandinavian Stroke Scale, and 30-day CT infarct volumes) compared with placebo. Subgroup analysis showed a similar lack of treatment effect in patients treated early (<6 hours) and in those treated later (6 to 12 hours). Somnolence was an expected pharmacological effect of clomethiazole, and this occurred during treatment as an adverse event in half of the patients randomly assigned to study drug.

Conclusions— The target population was selected, and sufficient drug was given to produce the expected pharmacological effect in the brain. Clomethiazole does not improve outcome in patients with major ischemic stroke.

Editorial Comment

Final Results

Graeme J. Hankey, MBBS, MD, FRCP, FRCP(Edin), FRACP, Guest Editor

Royal Perth Hospital, Department of Medicine, University of Western Australia, Perth, Western Australia

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