{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:01:40Z","timestamp":1791295300625,"version":"4.1.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic>Background and Purpose\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Numerous preclinical findings and a clinical pilot study suggest that recombinant human erythropoietin (EPO) provides neuroprotection that may be beneficial for the treatment of patients with ischemic stroke. Although EPO has been considered to be a safe and well-tolerated drug over 2 decades, recent studies have identified increased thromboembolic complications and\/or mortality risks on EPO administration to patients with cancer or chronic kidney disease. Accordingly, the double-blind, placebo-controlled, randomized German Multicenter EPO Stroke Trial (Phase II\/III; ClinicalTrials.gov Identifier: NCT00604630) was designed to evaluate efficacy and safety of EPO in stroke.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Methods\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    This clinical trial enrolled 522 patients with acute ischemic stroke in the middle cerebral artery territory (intent-to-treat population) with 460 patients treated as planned (per-protocol population). Within 6 hours of symptom onset, at 24 and 48 hours, EPO was infused intravenously (40 000 IU each). Systemic thrombolysis with recombinant tissue plasminogen activator was allowed and stratified for.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Results\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Unexpectedly, a very high number of patients received recombinant tissue plasminogen activator (63.4%). On analysis of total intent-to-treat and per-protocol populations, neither primary outcome Barthel Index on Day 90 (\n                    <jats:italic>P<\/jats:italic>\n                    =0.45) nor any of the other outcome parameters showed favorable effects of EPO. There was an overall death rate of 16.4% (n=42 of 256) in the EPO and 9.0% (n=24 of 266) in the placebo group (OR, 1.98; 95% CI, 1.16 to 3.38;\n                    <jats:italic>P<\/jats:italic>\n                    =0.01) without any particular mechanism of death unexpected after stroke.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Conclusions\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Based on analysis of total intent-to-treat and per-protocol populations only, this is a negative trial that also raises safety concerns, particularly in patients receiving systemic thrombolysis.\n                  <\/jats:p>","DOI":"10.1161\/strokeaha.109.564872","type":"journal-article","created":{"date-parts":[[2009,10,15]],"date-time":"2009-10-15T21:45:55Z","timestamp":1255643155000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":497,"title":["Recombinant Human Erythropoietin in the Treatment of Acute Ischemic Stroke"],"prefix":"10.1161","volume":"40","author":[{"given":"Hannelore","family":"Ehrenreich","sequence":"first","affiliation":[{"name":"From the Division of Clinical Neuroscience (H.E., M.W., C.B.), Max Planck Institute of Experimental Medicine, Go\u0308ttingen, Germany; Center for Neurological Medicine (K.W., R.D.), Hannover Medical School, Hannover, Germany; the Department of Neurology (H.P., M.B., A.K.), University Medical Center Go\u0308ttingen, Georg-August-University, Go\u0308ttingen, Germany; the Department of Neurology (D.S., A.W.), University Hospital of Leipzig, Leipzig, Germany; the Department of Neurology (C.W.), University of Duisburg..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Weissenborn","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Neuroscience (H.E., M.W., C.B.), Max Planck Institute of Experimental Medicine, Go\u0308ttingen, Germany; Center for Neurological Medicine (K.W., R.D.), Hannover Medical School, Hannover, Germany; the Department of Neurology (H.P., M.B., A.K.), University Medical Center Go\u0308ttingen, Georg-August-University, Go\u0308ttingen, Germany; the Department of Neurology (D.S., A.W.), University Hospital of Leipzig, Leipzig, Germany; the Department of Neurology (C.W.), University of Duisburg..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilmar","family":"Prange","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Neuroscience (H.E., M.W., C.B.), Max Planck Institute of Experimental Medicine, Go\u0308ttingen, Germany; Center for Neurological Medicine (K.W., R.D.), Hannover Medical School, Hannover, Germany; the Department of Neurology (H.P., M.B., A.K.), University Medical Center Go\u0308ttingen, Georg-August-University, Go\u0308ttingen, Germany; the Department of Neurology (D.S., A.W.), University Hospital of Leipzig, Leipzig, Germany; the Department of Neurology (C.W.), University of Duisburg..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar","family":"Schneider","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Neuroscience (H.E., M.W., C.B.), Max Planck Institute of Experimental Medicine, Go\u0308ttingen, Germany; Center for Neurological Medicine (K.W., R.D.), Hannover Medical School, Hannover, Germany; the Department of Neurology (H.P., M.B., A.K.), University Medical Center Go\u0308ttingen, Georg-August-University, Go\u0308ttingen, Germany; the Department of Neurology (D.S., A.W.), University Hospital of Leipzig, Leipzig, Germany; the Department of Neurology (C.W.), University of Duisburg..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Weimar","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Neuroscience (H.E., M.W., C.B.), Max Planck Institute of Experimental Medicine, Go\u0308ttingen, Germany; Center for Neurological Medicine (K.W., R.D.), Hannover Medical School, Hannover, Germany; the Department of Neurology (H.P., M.B., A.K.), University Medical Center Go\u0308ttingen, Georg-August-University, Go\u0308ttingen, Germany; the Department of Neurology (D.S., A.W.), University Hospital of Leipzig, Leipzig, Germany; the Department of Neurology (C.W.), University of Duisburg..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Wartenberg","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Neuroscience (H.E., M.W., C.B.), Max Planck Institute of Experimental Medicine, Go\u0308ttingen, Germany; Center for Neurological Medicine (K.W., R.D.), Hannover Medical School, Hannover, Germany; the Department of Neurology (H.P., M.B., A.K.), University Medical Center Go\u0308ttingen, Georg-August-University, Go\u0308ttingen, Germany; the Department of Neurology (D.S., A.W.), University Hospital of Leipzig, Leipzig, Germany; the Department of Neurology (C.W.), University of Duisburg..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Schellinger","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Neuroscience (H.E., M.W., C.B.), Max Planck Institute of Experimental Medicine, Go\u0308ttingen, Germany; Center for Neurological Medicine (K.W., R.D.), Hannover Medical School, Hannover, Germany; the Department of Neurology (H.P., M.B., A.K.), University Medical Center Go\u0308ttingen, Georg-August-University, Go\u0308ttingen, Germany; the Department of Neurology (D.S., A.W.), University Hospital of Leipzig, Leipzig, Germany; the Department of Neurology (C.W.), University of Duisburg..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Bohn","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Neuroscience (H.E., M.W., C.B.), Max Planck Institute of Experimental Medicine, Go\u0308ttingen, Germany; Center for Neurological Medicine (K.W., R.D.), Hannover Medical School, Hannover, Germany; the Department of Neurology (H.P., M.B., A.K.), University Medical Center Go\u0308ttingen, Georg-August-University, Go\u0308ttingen, Germany; the Department of Neurology (D.S., A.W.), University Hospital of Leipzig, Leipzig, Germany; the Department of Neurology (C.W.), University of Duisburg..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Becker","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Neuroscience (H.E., M.W., C.B.), Max Planck Institute of Experimental Medicine, Go\u0308ttingen, Germany; Center for Neurological Medicine (K.W., R.D.), Hannover Medical School, Hannover, Germany; the Department of Neurology (H.P., M.B., A.K.), University Medical Center Go\u0308ttingen, Georg-August-University, Go\u0308ttingen, Germany; the Department of Neurology (D.S., A.W.), University Hospital of Leipzig, Leipzig, Germany; the Department of Neurology (C.W.), University of Duisburg..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Wegrzyn","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Neuroscience (H.E., M.W., C.B.), Max Planck Institute of Experimental Medicine, Go\u0308ttingen, Germany; Center for Neurological Medicine (K.W., R.D.), Hannover Medical School, Hannover, Germany; the Department of Neurology (H.P., M.B., A.K.), University Medical Center Go\u0308ttingen, Georg-August-University, Go\u0308ttingen, Germany; the Department of Neurology (D.S., A.W.), University Hospital of Leipzig, Leipzig, Germany; the Department of Neurology (C.W.), University of Duisburg..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Ja\u0308hnig","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Neuroscience (H.E., M.W., C.B.), Max Planck Institute of Experimental Medicine, Go\u0308ttingen, Germany; Center for Neurological Medicine (K.W., R.D.), Hannover Medical School, Hannover, Germany; the Department of Neurology (H.P., M.B., A.K.), University Medical Center Go\u0308ttingen, Georg-August-University, Go\u0308ttingen, Germany; the Department of Neurology (D.S., A.W.), University Hospital of Leipzig, Leipzig, Germany; the Department of Neurology (C.W.), University of Duisburg..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Herrmann","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Neuroscience (H.E., M.W., C.B.), Max Planck Institute of Experimental Medicine, Go\u0308ttingen, Germany; Center for Neurological Medicine (K.W., R.D.), Hannover Medical School, Hannover, Germany; the Department of Neurology (H.P., M.B., A.K.), University Medical Center Go\u0308ttingen, Georg-August-University, Go\u0308ttingen, Germany; the Department of Neurology (D.S., A.W.), University Hospital of Leipzig, Leipzig, Germany; the Department of Neurology (C.W.), University of Duisburg..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Knauth","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Neuroscience (H.E., M.W., C.B.), Max Planck Institute of Experimental Medicine, Go\u0308ttingen, Germany; Center for Neurological Medicine (K.W., R.D.), Hannover Medical School, Hannover, Germany; the Department of Neurology (H.P., M.B., A.K.), University Medical Center Go\u0308ttingen, Georg-August-University, Go\u0308ttingen, Germany; the Department of Neurology (D.S., A.W.), University Hospital of Leipzig, Leipzig, Germany; the Department of Neurology (C.W.), University of Duisburg..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Ba\u0308hr","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Neuroscience (H.E., M.W., C.B.), Max Planck Institute of Experimental Medicine, Go\u0308ttingen, Germany; Center for Neurological Medicine (K.W., R.D.), Hannover Medical School, Hannover, Germany; the Department of Neurology (H.P., M.B., A.K.), University Medical Center Go\u0308ttingen, Georg-August-University, Go\u0308ttingen, Germany; the Department of Neurology (D.S., A.W.), University Hospital of Leipzig, Leipzig, Germany; the Department of Neurology (C.W.), University of Duisburg..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Heide","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Neuroscience (H.E., M.W., C.B.), Max Planck Institute of Experimental Medicine, Go\u0308ttingen, Germany; 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