{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:32:26Z","timestamp":1790706746499,"version":"4.1.0"},"reference-count":24,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neonatology"],"published-print":{"date-parts":[[2019]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background and Objectives:&lt;\/i&gt;&lt;\/b&gt; Therapeutic interventions to improve the efficacy of whole-body cooling for hypoxic-ischemic encephalopathy (HIE) are desirable. Topiramate has been effective in reducing brain damage in experimental studies. However, in the clinical setting information is limited to a small number of feasibility trials. We launched a randomized controlled double-blinded topiramate\/placebo multicenter trial with the primary objective being to reduce the antiepileptic activity in cooled neonates with HIE and assess if brain damage would be reduced as a consequence. &lt;b&gt;&lt;i&gt;Study Design:&lt;\/i&gt;&lt;\/b&gt; Neonates were randomly assigned to topiramate or placebo at the initiation of hypothermia. Topiramate was administered via a nasogastric tube. Brain electric activity was continuously monitored. Topiramate pharmacokinetics, energy-related and Krebs\u2019 cycle intermediates, and lipid peroxidation biomarkers were determined using liquid chromatography-mass spectrometry and MRI for assessing brain damage. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; Out of 180 eligible patients 110 were randomized, 57 (51.8%) to topiramate and 53 (48.2%) to placebo. No differences in the perinatal or postnatal variables were found. The topiramate group exhibited less seizure burden in the first 24 h of hypothermia (topiramate, &lt;i&gt;n&lt;\/i&gt; = 14 [25.9%] vs. placebo, &lt;i&gt;n&lt;\/i&gt; = 22 [42%]); needed less additional medication, and had lower mortality (topiramate, &lt;i&gt;n&lt;\/i&gt; = 5 [9.2%] vs. placebo, &lt;i&gt;n&lt;\/i&gt; = 10 [19.2%]); however, these results did not achieve statistical significance. Topiramate achieved a therapeutic range in 37.5 and 75.5% of the patients at 24 and 48 h, respectively. A significant association between serum topiramate levels and seizure activity (&lt;i&gt;p&lt;\/i&gt; &amp;#x3c; 0.016) was established. No differences for oxidative stress, energy-related metabolites, or MRI were found. &lt;b&gt;&lt;i&gt;Conclusions:&lt;\/i&gt;&lt;\/b&gt; Topiramate reduced seizures in patients achieving therapeutic levels in the first hours after treatment initiation; however, they represented only a part of the study population. Our results warrant further studies with higher loading and maintenance dosing of topiramate.<\/jats:p>","DOI":"10.1159\/000499084","type":"journal-article","created":{"date-parts":[[2019,5,15]],"date-time":"2019-05-15T21:01:12Z","timestamp":1557954072000},"page":"76-84","source":"Crossref","is-referenced-by-count":47,"title":["Topiramate plus Cooling for Hypoxic-Ischemic Encephalopathy: A Randomized, Controlled, Multicenter, Double-Blinded Trial"],"prefix":"10.1159","volume":"116","author":[{"given":"Antonio","family":"Nu\u00f1ez-Ramiro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9276-1912","authenticated-orcid":false,"given":"Isabel","family":"Benavente-Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Valverde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malaika","family":"Cordeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorotea","family":"Blanco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector","family":"Boix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Caba\u00f1as","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Chaffanel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bel\u00e9n","family":"Fern\u00e1ndez-Colomer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose\u00a0Ram\u00f3n","family":"Fern\u00e1ndez-Lorenzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Kuligowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"Loureiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria\u00a0Teresa","family":"Moral-Pumarega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Pav\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7630-0614","authenticated-orcid":false,"given":"Angel","family":"S\u00e1nchez-Illana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e9s","family":"Tof\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Herv\u00e1s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Garc\u00eda-Robles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Parra-Llorca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Cernada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Martinez-Rodilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Lorente-Pozo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Llorens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remedios","family":"Marqu\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0061-4742","authenticated-orcid":false,"given":"M\u00e1ximo","family":"Vento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on\u00a0behalf\u00a0of\u00a0the\u00a0Hypotop\u00a0Study\u00a0Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2019,5,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2018.01.010"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.03.011"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70016-3"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2015-309639"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2014.00040"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2005.086314"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2013-305206"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.3390\/ijms160922368"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2011.01.006"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2010.04.019"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcps050929"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1542\/neo.7-2-e76"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1111\/apa.12287"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2009.01659.x"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70295-9"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17202-7"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-014-7824-6"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01561.x"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2017.07.008"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02302.x"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2628027100"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2002.tb01633.x"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2014.253"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1038\/nature13909"}],"container-title":["Neonatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/499084","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/499084","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:24:47Z","timestamp":1745425487000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000499084"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,7,12]]},"published-print":{"date-parts":[[2019,7,25]]}},"URL":"https:\/\/doi.org\/10.1159\/000499084","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.8131547","asserted-by":"subject"}]},"ISSN":["1661-7800","1661-7819"],"issn-type":[{"value":"1661-7800","type":"print"},{"value":"1661-7819","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019]]}}}