{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T23:55:26Z","timestamp":1788652526731,"version":"build-2803163510"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["RS-2024-00335934"],"award-info":[{"award-number":["RS-2024-00335934"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u2011 2021R1A2C2014304"],"award-info":[{"award-number":["NRF\u2011 2021R1A2C2014304"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Systemic ischemic-reperfusion injury following cardiac arrest results in multisystem organ failure, brain injury and death. The aim of this trial is to investigate whether the combined use of cortisol, ascorbic acid (vitamin C), and thiamine during the early post-resuscitation period reduces the neurologic injury among out-of-hospital cardiac arrest (OHCA) survivors treated with targeted temperature management (TTM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>This is a single-blind, multi-center, randomized, placebo-controlled trial to be conducted in nine tertiary university-affiliated hospitals in South Korea. A total of 160 OHCA survivors treated with TTM will be randomly assigned to the treatment or control groups (1:1 ratio). For the treatment group, patients will intravenously receive a combination dose of ascorbic acid (50\u2009mg\/kg, maximum single dose 3\u2009g), thiamine (200\u2009mg), and cortisol (100\u2009mg) that will be mixed in three separate 50mL bags of 0.9% saline, respectively, every 12 hours for 3 days. For the placebo group, patients will receive three separate 50mL bags of 0.9% saline intravenously in the same manner. The primary outcome is the peak neuron-specific enolase level at 48\u201372 hours after the return of spontaneous circulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The potential benefits of ascorbic acid, thiamine, and cortisol as neuroprotective agents have been reported in previous preclinical trials. This trial is the first clinical trial to assess the neuroprotective effectiveness of a combination of ascorbic acid, thiamine, and cortisol for OHCA survivors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04921189\" xlink:type=\"simple\">NCT<\/jats:ext-link>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04921189\" xlink:type=\"simple\">04921189<\/jats:ext-link>\n                    <\/jats:p>\n                  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Hwan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6904-5966","authenticated-orcid":true,"given":"Won Young","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"pone.0319733.ref001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.resuscitation.2021.02.003","article-title":"European Resuscitation Council Guidelines 2021: Executive summary","volume":"161","author":"GD Perkins","year":"2021","journal-title":"Resuscitation"},{"issue":"12","key":"pone.0319733.ref002","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1007\/s00134-021-06548-2","article-title":"Brain injury after cardiac arrest: pathophysiology, treatment, and prognosis","volume":"47","author":"C Sandroni","year":"2021","journal-title":"Intensive Care 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