{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:55:28Z","timestamp":1790394928088,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,11,14]],"date-time":"2016-11-14T00:00:00Z","timestamp":1479081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001858","name":"VINNOVA","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003793","name":"Hj\u00e4rt-Lungfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003793","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Imatinib, a tyrosine kinase inhibitor, has been shown to restore blood\u2013brain barrier integrity and reduce infarct size, haemorrhagic transformation and cerebral oedema in stroke models treated with tissue plasminogen activator. We evaluated the safety of imatinib, based on clinical and neuroradiological data, and its potential influence on neurological and functional outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A phase II randomized trial was performed in patients with acute ischaemic stroke treated with intravenous thrombolysis. A total of 60 patients were randomly assigned to four groups [3 (active): 1 (control)]; the active treatment groups received oral imatinib for 6 days at three dose levels (400, 600 and 800 mg). Primary outcome was any adverse event; secondary outcomes were haemorrhagic transformation, cerebral oedema, neurological severity on the National Institutes of Health Stroke Scale (NIHSS) at 7 days and at 3 months and functional outcomes on the modified Rankin scale (mRS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Four serious adverse events were reported, which resulted in three deaths (one in the control group and two in the 400\u2010mg dose group; one patient in the latter group did not receive active treatment and the other received two doses). Nonserious adverse events were mostly mild, resulting in full recovery. Imatinib ameliorated neurological outcomes with an improvement of 0.6 NIHSS points per 100 mg imatinib (<jats:italic>P<\/jats:italic>= 0.02). For the 800\u2010mg group, the mean unadjusted and adjusted NIHSS improvements were 4 (<jats:italic>P<\/jats:italic>= 0.037) and 5 points (<jats:italic>P<\/jats:italic>= 0.012), respectively, versus controls. Functional independence (mRS 0\u20132) increased by 18% versus controls (61 vs. 79;<jats:italic>P<\/jats:italic>= 0.296).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This phase II study showed that imatinib is safe and tolerable and may reduce neurological disability in patients treated with intravenous thrombolysis after ischaemic stroke. A confirmatory randomized trial is currently underway.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.12576","type":"journal-article","created":{"date-parts":[[2016,11,14]],"date-time":"2016-11-14T18:13:31Z","timestamp":1479147211000},"page":"273-283","source":"Crossref","is-referenced-by-count":62,"title":["Randomized assessment of imatinib in patients with acute ischaemic stroke treated with intravenous thrombolysis"],"prefix":"10.1111","volume":"281","author":[{"given":"N.","family":"Wahlgren","sequence":"first","affiliation":[{"name":"Department of Neurology Karolinska University Hospital Stockholm Sweden"},{"name":"Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Thor\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Neurology Karolinska University Hospital Stockholm Sweden"},{"name":"Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"H\u00f6jeberg","sequence":"additional","affiliation":[{"name":"Department of Neurology Capio St G\u00f6ran Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.\u2010B.","family":"K\u00e4ll","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine S\u00f6dersjukhuset Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.\u2010C.","family":"Laska","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Danderyd Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Sj\u00f6strand","sequence":"additional","affiliation":[{"name":"Department of Neurology Karolinska University Hospital Stockholm Sweden"},{"name":"Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"H\u00f6ijer","sequence":"additional","affiliation":[{"name":"Unit of Biostatistics Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Almqvist","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden"},{"name":"Department of Neuroradiology Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Holmin","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden"},{"name":"Department of Neuroradiology Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Lilja","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden"},{"name":"Department of Neuroradiology Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Fredriksson","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Cardiovascular Medicine University of Michigan Medical School Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Neurology Karolinska University Hospital Stockholm Sweden"},{"name":"Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,11,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/S0022-3565(24)38186-8","article-title":"Combination of hypoxia\/aglycemia compromises in vitro blood\u2010brain barrier integrity","volume":"289","author":"Abbruscato TJ","year":"1999","journal-title":"J Pharmacol ExpTher"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1999.276.4.C812"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00645.2001"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20199"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2008.08.005"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.608257"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03402.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1109766"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.551341"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1787"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600397"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M503388200"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2012.10.072"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-014-0358-6"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199512143332401"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03530130023023"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60149-4"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0804656"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61339-2"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.192535"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60491-6"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60768-5"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60584-5"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1411587"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1414905"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1414792"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1415061"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1503780"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1177\/1747493015609778"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1515\/jem-2014-0011"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.2427\/8758"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa062867"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.10.018"}],"container-title":["Journal of Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjoim.12576","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjoim.12576","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/joim.12576","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T14:29:39Z","timestamp":1749738579000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/joim.12576"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,14]]},"references-count":33,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017,3]]}},"alternative-id":["10.1111\/joim.12576"],"URL":"https:\/\/doi.org\/10.1111\/joim.12576","archive":["Portico"],"relation":{},"ISSN":["0954-6820","1365-2796"],"issn-type":[{"value":"0954-6820","type":"print"},{"value":"1365-2796","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,14]]}}}