{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:12:26Z","timestamp":1791231146386,"version":"4.1.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>DP-b99, a lipophilic moderate-affinity chelator of zinc, was postulated to improve recovery after acute ischemic stroke. We evaluated the safety and therapeutic effects of DP-b99 in patients with acute hemispheric ischemic stroke.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>The Membrane-Activated Chelator Stroke Intervention trial was a randomized, double-blind, placebo-controlled, multicenter, parallel-group trial of intravenous DP-b99 administered for 4 consecutive days (NCT00893867). Acute ischemic stroke patients within 9 hours of onset, but untreated by alteplase, with a baseline National Institutes of Health Stroke Scale score of 10 to 16, and evidence of language dysfunction, visual field defect, and neglect were eligible. The primary efficacy analysis compared distributions of functional status measured by modified Rankin score in the intent-to-treat population of patients with any post-treatment outcome, adjusted for initial severity. Functional and neurological recovery were secondary measures. Home time was an exploratory end point.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>\n              Enrollment terminated at n=446 after the planned interim analysis determined futility; follow-up continued. Final modified Rankin score distributions were equal between DP-b99 and placebo-treated groups (\n              <jats:italic>P<\/jats:italic>\n              =0.10;\n              <jats:italic>P<\/jats:italic>\n              <jats:sub>adj<\/jats:sub>\n              adjusted for baseline age and National Institutes of Health Stroke Scale=0.21). Fewer patients recovered to modified Rankin score \u22641 in the DP-b99\u2013treated group (45\/218; 20.6%) than after placebo (63\/219; 28.8%) (\n              <jats:italic>P<\/jats:italic>\n              =0.05;\n              <jats:italic>P<\/jats:italic>\n              <jats:sub>adj<\/jats:sub>\n              =0.10). Similarly, fewer patients attained National Institutes of Health Stroke Scale \u22641 after DP-b99 (42\/218; 19.3%) than placebo (56\/219; 25.6%;\n              <jats:italic>P<\/jats:italic>\n              =0.10;\n              <jats:italic>P<\/jats:italic>\n              <jats:sub>adj<\/jats:sub>\n              =0.26). Mortality was similar between DP-b99 and placebo intent-to-treat groups (36\/218; 16.5% vs 33\/219; 15.1%;\n              <jats:italic>P<\/jats:italic>\n              =0.68). Home time was unchanged by treatment (median 36 vs 36.5 days;\n              <jats:italic>P<\/jats:italic>\n              =0.25).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Despite encouraging preclinical and phase II trial data, DP-b99 shows no evidence of efficacy in treating human ischemic stroke.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.111.000013","type":"journal-article","created":{"date-parts":[[2013,2,8]],"date-time":"2013-02-08T02:50:59Z","timestamp":1360291859000},"page":"580-584","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Results of Membrane-activated Chelator Stroke Intervention Randomized Trial of DP-b99 in Acute Ischemic Stroke"],"prefix":"10.1161","volume":"44","author":[{"given":"Kennedy R.","family":"Lees","sequence":"first","affiliation":[{"name":"From the Acute Stroke Unit and Cerebrovascular Clinic, University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary and Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom (K.R.L.); Department of Neurology, Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel (N.B.); Department of Neurology, University of Duisburg-Essen, Essen, Germany (H.-C.D); Department of Neurology and Rehabilitation, University of Illinois College of Medicine at Chicago,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natan","family":"Bornstein","sequence":"additional","affiliation":[{"name":"From the Acute Stroke Unit and Cerebrovascular Clinic, University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary and Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom (K.R.L.); Department of Neurology, Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel (N.B.); Department of Neurology, University of Duisburg-Essen, Essen, Germany (H.-C.D); Department of Neurology and Rehabilitation, University of Illinois College of Medicine at Chicago,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Christoph","family":"Diener","sequence":"additional","affiliation":[{"name":"From the Acute Stroke Unit and Cerebrovascular Clinic, University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary and Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom (K.R.L.); Department of Neurology, Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel (N.B.); Department of Neurology, University of Duisburg-Essen, Essen, Germany (H.-C.D); Department of Neurology and Rehabilitation, University of Illinois College of Medicine at Chicago,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip B.","family":"Gorelick","sequence":"additional","affiliation":[{"name":"From the Acute Stroke Unit and Cerebrovascular Clinic, University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary and Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom (K.R.L.); Department of Neurology, Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel (N.B.); Department of Neurology, University of Duisburg-Essen, Essen, Germany (H.-C.D); Department of Neurology and Rehabilitation, University of Illinois College of Medicine at Chicago,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilad","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"From the Acute Stroke Unit and Cerebrovascular Clinic, University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary and Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom (K.R.L.); Department of Neurology, Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel (N.B.); Department of Neurology, University of Duisburg-Essen, Essen, Germany (H.-C.D); Department of Neurology and Rehabilitation, University of Illinois College of Medicine at Chicago,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashfaq","family":"Shuaib","sequence":"additional","affiliation":[{"name":"From the Acute Stroke Unit and Cerebrovascular Clinic, University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary and Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom (K.R.L.); Department of Neurology, Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel (N.B.); Department of Neurology, University of Duisburg-Essen, Essen, Germany (H.-C.D); Department of Neurology and Rehabilitation, University of Illinois College of Medicine at Chicago,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199512143332401"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0804656"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60491-6"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.21.2003"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000258112.14918.24"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02326-6"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.31.11.2543"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.31.9.2257"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/hs0102.101478"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)15490-1"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa052980"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa070240"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.2119\/2007-00044.Galasso"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2009.07.019"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.10083"},{"key":"e_1_3_2_17_2","first-page":"234 (abstract)","article-title":"The effect of DP-b99, a lipophilic divalent transition metal chelator, on Matrix Metalloproteinases-2 and-9 activity in a rat MCAO ischemic model.","volume":"10","author":"Striem S","year":"2003","unstructured":"Striem S, Schatz G, Krakovsky M, Finkelstein E, Kozak A, Angel I, Friedman JE. The effect of DP-b99, a lipophilic divalent transition metal chelator, on Matrix Metalloproteinases-2 and-9 activity in a rat MCAO ischemic model. Neural Plast. 2003;10:234 (abstract).","journal-title":"Neural Plast."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.107.506378"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-4949.2011.00608.x"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.107.181486"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1159\/000131083"},{"key":"e_1_3_2_22_2","first-page":"246","volume-title":"Analysis of Clinical Trials Using SAS: A Practical Guide","author":"Dmitrienko A","year":"2005","unstructured":"Dmitrienko A, Molenbergh G, Chuang-Stein C, Offen W. Analysis of Clinical Trials Using SAS: A Practical Guide. 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