{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:34:07Z","timestamp":1790764447345,"version":"4.1.0"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background and Purpose\u2014<\/jats:italic>\n            <\/jats:bold>\n            DP-b99 is a chelator of zinc and calcium ions that acts selectively within cell membranes and has neuroprotective properties in animal models of stroke. We present the results of a multicenter, double-blind, placebo-controlled, randomized trial to assess the safety and potential protective effects of DP-b99 in acute ischemic stroke.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods\u2014<\/jats:italic>\n            <\/jats:bold>\n            One hundred and fifty stroke patients with signs of cortical involvement and a National Institutes of Health Stroke Scale (NIHSS) score of 7 to 20 received a 4-day course of intravenous 1 mg\/kg per day DP-b99 or placebo within 1 to 9 hours of stroke onset. Treatment with recombinant tissue plasminogen activator was not allowed.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            No major differences in mortality rate, causes of death, adverse events, safety laboratory tests, and ECG parameters were found between the 2 groups. The baseline NIHSS score of the 72 DP-b99\u2013 and 75 placebo-treated patients in the intent-to-treat cohort was (mean\u00b1SD) 12.2\u00b14.0 and 12.6\u00b13.3, respectively; the time to needle (mean\u00b1SD) was 6:36\u00b11:47 and 6:28\u00b11:33 hours, respectively; and the age (mean\u00b1SD) was 73.3\u00b19.9 and 72.0\u00b19.6 years, respectively. The 90-day median change from baseline (the primary end point) was \u22126.0 and \u22125.0 NIHSS points in the DP-b99 and placebo groups, respectively (nonsignificant). At 90 days, there was a significantly better outcome in the DP-b99 group compared with the placebo group (modified Rankin scale score of 0, 1, or same as prestroke): 30.6% and 16.0%, respectively (\n            <jats:italic>P<\/jats:italic>\n            =0.05). The recovery rate was unaffected by the time to needle. Further analyses indicated that the 90-day median change from baseline in patients with an entry NIHSS score of 10 to 16 was 8.0 and 5.0 points in the DP-b99 and placebo groups, respectively (\n            <jats:italic>P<\/jats:italic>\n            =0.03).\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            In this small-scale study, the primary end point of change in NIHSS score from baseline to 90 days was not met. However, secondary end points demonstrated a significantly improved 90-day recovery rate with treatment with DP-b99 when compared with placebo. In addition, in patients with baseline NIHSS scores of 10 to 16, a significant post hoc change in NIHSS score from baseline to day 90 was observed. No major safety problems were identified. These findings need to be confirmed with a larger prospective study of strokes involving the cortex.\n          <\/jats:p>","DOI":"10.1161\/strokeaha.107.506378","type":"journal-article","created":{"date-parts":[[2008,4,11]],"date-time":"2008-04-11T01:55:00Z","timestamp":1207878900000},"page":"1774-1778","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":60,"title":["DP-b99, a Membrane-Activated Metal Ion Chelator, as Neuroprotective Therapy in Ischemic Stroke"],"prefix":"10.1161","volume":"39","author":[{"given":"Hans-Christoph","family":"Diener","sequence":"first","affiliation":[{"name":"From the Department of Neurology (H.C.D.), University of Duisburg-Essen, Essen, Germany; Neurologic ICU and Stroke Unit (D.S.), University of Leipzig, Leipzig, Germany; Department of Neurology (Y.L.), Edith Wolfson Medical Center, Holon and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Neurology (N.M.B.), Tel Aviv Medical Center and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; and D-Pharm Ltd (A.K., G.R.), Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar","family":"Schneider","sequence":"additional","affiliation":[{"name":"From the Department of Neurology (H.C.D.), University of Duisburg-Essen, Essen, Germany; Neurologic ICU and Stroke Unit (D.S.), University of Leipzig, Leipzig, Germany; Department of Neurology (Y.L.), Edith Wolfson Medical Center, Holon and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Neurology (N.M.B.), Tel Aviv Medical Center and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; and D-Pharm Ltd (A.K., G.R.), Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yair","family":"Lampl","sequence":"additional","affiliation":[{"name":"From the Department of Neurology (H.C.D.), University of Duisburg-Essen, Essen, Germany; Neurologic ICU and Stroke Unit (D.S.), University of Leipzig, Leipzig, Germany; Department of Neurology (Y.L.), Edith Wolfson Medical Center, Holon and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Neurology (N.M.B.), Tel Aviv Medical Center and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; and D-Pharm Ltd (A.K., G.R.), Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natan M.","family":"Bornstein","sequence":"additional","affiliation":[{"name":"From the Department of Neurology (H.C.D.), University of Duisburg-Essen, Essen, Germany; Neurologic ICU and Stroke Unit (D.S.), University of Leipzig, Leipzig, Germany; Department of Neurology (Y.L.), Edith Wolfson Medical Center, Holon and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Neurology (N.M.B.), Tel Aviv Medical Center and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; and D-Pharm Ltd (A.K., G.R.), Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Kozak","sequence":"additional","affiliation":[{"name":"From the Department of Neurology (H.C.D.), University of Duisburg-Essen, Essen, Germany; Neurologic ICU and Stroke Unit (D.S.), University of Leipzig, Leipzig, Germany; Department of Neurology (Y.L.), Edith Wolfson Medical Center, Holon and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Neurology (N.M.B.), Tel Aviv Medical Center and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; and D-Pharm Ltd (A.K., G.R.), Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilad","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"From the Department of Neurology (H.C.D.), University of Duisburg-Essen, Essen, Germany; Neurologic ICU and Stroke Unit (D.S.), University of Leipzig, Leipzig, Germany; Department of Neurology (Y.L.), Edith Wolfson Medical Center, Holon and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Neurology (N.M.B.), Tel Aviv Medical Center and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; and D-Pharm Ltd (A.K., G.R.), Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)15692-4"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20741"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa052980"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000249410.91473.44"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa070240"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/399a007"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.10083"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","unstructured":"Krakovsky M Polyak M Angel I Kozak A. 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