{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:59:26Z","timestamp":1790362766995,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0014736","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000}}],"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009898","name":"Defense Health Agency","doi-asserted-by":"publisher","award":["W81XWH22C0030"],"award-info":[{"award-number":["W81XWH22C0030"]}],"id":[{"id":"10.13039\/100009898","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","award":["R01 FD007839"],"award-info":[{"award-number":["R01 FD007839"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Snakebite envenoming causes an estimated 81,000\u2013138,000 deaths and more than 400,000 cases of permanent disability each year, disproportionately affecting low-resource regions. Antivenom is the only approved treatment but requires intravenous administration. We evaluated intravenous followed by oral varespladib as adjunctive therapy to antivenom in hospitalized patients with snakebite envenoming.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>\n                      In this multicenter, randomized, double-blind, placebo-controlled phase II trial in India (CTRI\/2023\/10\/058782) and the USA (NCT05717062), patients with snakebite envenoming were randomly assigned (1:1) to receive varespladib or placebo, both in addition to standard of care including antivenom. For elapid envenoming, the primary endpoint was time to recovery of 5-second head-lift. For viper envenoming, the primary endpoint was area under the curve (AUC) from baseline to Day 14 of a 3-item Snakebite Severity Score (SSS). Between June 3\n                      <jats:sup>rd<\/jats:sup>\n                      , 2023, and October 19\n                      <jats:sup>th<\/jats:sup>\n                      , 2024, 140 patients were randomized and 139 were analyzed (73 varespladib; 66 placebo). Study drug was initiated a mean of 7.3 hours after the bite and 3.3 hours after antivenom. Among elapid-bite patients, mean time to head-lift recovery was 27.6 hours with varespladib vs. 36.2 hours with placebo (p\u2009=\u20090.6). Among viper-bite patients, SSS AUC to Day 14 was 660 with varespladib vs. 629 with placebo (p\u2009=\u20090.7). No serious adverse event occurred with varespladib.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this trial in which varespladib was initiated on average 7 hours after snakebite and several hours after antivenom, late adjunctive varespladib did not meet the primary endpoint. Interpretation of these results is limited by heterogeneity in the snake species responsible for envenoming and the associated differences in venom composition, clinical manifestations, and antivenom treatments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0014736","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:02:32Z","timestamp":1790013752000},"page":"e0014736","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adjunctive Varespladib after antivenom administration for snakebite: A phase II randomized clinical trial"],"prefix":"10.1371","volume":"20","author":[{"given":"Charles J.","family":"Gerardo","sequence":"first","affiliation":[{"name":"Duke University Hospital","place":["Durham, North Carolina, United States of 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