{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:13:18Z","timestamp":1791231198257,"version":"4.1.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2002,1]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:bold>\n                  <jats:italic>Background and Purpose<\/jats:italic>\n                <\/jats:bold>\n                \u2014\n              <\/jats:italic>\n            <\/jats:bold>\n            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.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:bold>\n                  <jats:italic>Methods<\/jats:italic>\n                <\/jats:bold>\n                \u2014\n              <\/jats:italic>\n            <\/jats:bold>\n            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 \u226560 at last follow-up as the primary outcome measure.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:bold>\n                  <jats:italic>Results<\/jats:italic>\n                <\/jats:bold>\n                \u2014\n              <\/jats:italic>\n            <\/jats:bold>\n            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\u00b15.2). Ninety-six percent were classified as total anterior circulation syndrome. The proportion of patients reaching a Barthel Index score of \u226560 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;\n            <jats:italic>P<\/jats:italic>\n            =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 (&lt;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.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:bold>\n                  <jats:italic>Conclusions<\/jats:italic>\n                <\/jats:bold>\n                \u2014\n              <\/jats:italic>\n            <\/jats:bold>\n            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.\n          <\/jats:p>","DOI":"10.1161\/hs0102.101478","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T23:16:47Z","timestamp":1027898207000},"page":"122-129","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":125,"title":["Clomethiazole Acute Stroke Study in Ischemic Stroke (CLASS-I)"],"prefix":"10.1161","volume":"33","author":[{"given":"P.","family":"Lyden","sequence":"first","affiliation":[{"name":"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 ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Shuaib","sequence":"additional","affiliation":[{"name":"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 ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Ng","sequence":"additional","affiliation":[{"name":"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 ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Levin","sequence":"additional","affiliation":[{"name":"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 ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.P.","family":"Atkinson","sequence":"additional","affiliation":[{"name":"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 ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Rajput","sequence":"additional","affiliation":[{"name":"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 ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Wechsler","sequence":"additional","affiliation":[{"name":"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 ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Ashwood","sequence":"additional","affiliation":[{"name":"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 ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Claesson","sequence":"additional","affiliation":[{"name":"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 ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Odergren","sequence":"additional","affiliation":[{"name":"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 ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Salazar-Grueso","sequence":"additional","affiliation":[{"name":"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 ..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)91658-U"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200009073431007"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.29.2.415"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.94.5.1167"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199710303371812"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.9.1151"},{"key":"e_1_3_2_7_2","first-page":"233","volume":"40","year":"1997","unstructured":"Lyden PD. GABA and neuroprotection. Int Rev Neurobiol. 1997; 40: 233\u2013258.","journal-title":"Int Rev Neurobiol"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(99)00233-6"},{"key":"e_1_3_2_9_2","first-page":"406","volume":"104","year":"1999","unstructured":"Cross AJ, Jones JA, Baldwin HA, Green AR. Neuroprotective activity of chlomethiazole following transient forebrain ischaemia in the gerbil. Br J Pharmacol. 1999; 104: 406\u2013411.","journal-title":"Br J Pharmacol"},{"key":"e_1_3_2_10_2","first-page":"121","volume":"156","year":"1998","unstructured":"Marshall JW, Cross AJ, Murray TK, Ridley RM. Clomethiazole treatment ameliorates the motor disability incurred by focal cerebral ischaemia in a non-human primate. Exp Neurol. 1998; 156: 121\u2013129.","journal-title":"Exp Neurol"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(99)00275-0"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/1055-8330(95)90022-5"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb14950.x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02071-0"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.30.1.21"},{"key":"e_1_3_2_16_2","first-page":"61","volume":"14","year":"1965","unstructured":"Mahoney FI, Barthel DW. Functional evaluation: the Barthel Index. Md Med J. 1965; 14: 61\u201365.","journal-title":"Md Med J"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1052-3057(99)80072-X"},{"key":"e_1_3_2_18_2","first-page":"158","volume":"9","year":"2000","unstructured":"Wahlgren N-G, Matias-Guiu J, Miguel Lainez J, Veloso F, Ranasinha K, Grossman E, Ashwood T, for the CLASS Study Group. The Clomethiazole Acute Stroke Study (CLASS): safety results in 1356 patients with hemispheric stroke. Stroke. 2000; 9: 158\u2013165.","journal-title":"Stroke"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1052-3057(98)80128-6"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.3109\/09638288809164105"},{"key":"e_1_3_2_21_2","first-page":"14","volume":"60","year":"1979","unstructured":"Granger CV, Devis LS, Peters MC, Sherwood CC, and Barrett JE. Stroke rehabilitation: analysis of repeated Barthel Index measures. Arch Phys Med Rehabil. 1979; 60: 14\u201317.","journal-title":"Arch Phys Med Rehabil"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1177\/003693305700200504"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.19.5.3363593"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.25.11.7974549"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.16.5.3901425"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1159\/000108825"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1159\/000109022"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)93206-O"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.24.1.35"},{"key":"e_1_3_2_30_2","first-page":"723","volume":"68","year":"1987","unstructured":"Shinar D, Gross CR, Bronstein KS, Licata-Gehr EE, Eden DT, Cabrera AR, Fishman IG, Roth AA, Barwick JA, Kunitz SC. Reliability of the activities of daily living scale and its use in the telephone interview. Arch Phys Med Rehabil. 1987; 68: 723\u2013728.","journal-title":"Arch Phys Med Rehabil"},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","unstructured":"Lyden P Broderick J Mascha L. Reliability of the Barthel Index Outcome Measure selected for the NINDS t-PA Stroke Trial.In: Yamaguchi T Mori E Minematsu K del Zoppo G eds. Thrombolytic Therapy in Acute Ischemic Stroke III. Tokyo Japan: Springer-Verlag; 1995: 327\u2013333.","DOI":"10.1007\/978-4-431-68459-6_39"},{"key":"e_1_3_2_32_2","unstructured":"Beal SL Sheiner LB. NONMEM User Guides. San Francisco Calif: NONMEM Project Group University of California; 1992."},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.25.7.8023352"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.27.4.599"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1159\/000015955"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.30.1.93"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.52.6.1125"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.21.2003"},{"key":"e_1_4_3_1_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.33.1.122"},{"key":"e_1_4_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.30.1.21"},{"key":"e_1_4_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)05847-0"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/hs0102.101478","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T02:11:15Z","timestamp":1715652675000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/hs0102.101478"}},"subtitle":["Final Results"],"short-title":[],"issued":{"date-parts":[[2002,1]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2002,1]]}},"alternative-id":["10.1161\/hs0102.101478"],"URL":"https:\/\/doi.org\/10.1161\/hs0102.101478","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,1]]},"assertion":[{"value":"2001-07-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-10-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-01-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}