03548nas a2200637   4500000000100000008004100001260004600042653001400088653001100102653001000113653001000123653001700133653001900150653001100169653001600180100001500196700001300211700001500224700001200239700001200251700001400263700001400277700001000291700001300301700001400314700001400328700001600342700001500358700001400373700001100387700001400398700001200412700001300424700001300437700001700450700001500467700001300482700001200495700001600507700001500523700001500538700001600553700001400569700001400583700001400597700001400611700001300625700002000638700001400658245011000672856009900782300001100881490000700892520199700899022001402896       2026                            d  c09/2026bPublic Library of Science (PLoS)10asnakebite10aSnakes10aViper10aIndia10aSnake venoms10aAdverse events10aToxins10aRattlesnake1 aGerardo CJ1 aBhalla A1 aMohanty CR1 aSahu BK1 aKumar S1 aAgrawal S1 aAyyan S M1 aShu E1 aDeuson T1 aKumar R M1 aBeatty NL1 aAkpunonu PD1 aShirazi FM1 aWatkins S1 aRuha A1 aVarney SM1 aGoel AK1 aGautam M1 aArnold J1 aBammigatti C1 aFrancis SJ1 aSelvam S1 aKumar H1 aAizenberg A1 aMicciche A1 aBledsoe RS1 aBoatright G1 aOomman SC1 aSamuel SP1 aWittes JT1 aCarter RW1 aLewin MR1 aPlatts-Mills TF1 aBhaumik S00aAdjunctive Varespladib after antivenom administration for snakebite: A phase II randomized clinical trial  uhttps://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0014736&type=printable  a1 - 150 v203 a<p><strong>Background</strong></p>

<p>Snakebite envenoming causes an estimated 81,000–138,000 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.</p>

<p><strong>Methods and findings</strong></p>

<p>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 rd , 2023, and October 19 th , 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 = 0.6). Among viper-bite patients, SSS AUC to Day 14 was 660 with varespladib vs. 629 with placebo (p = 0.7). No serious adverse event occurred with varespladib.</p>

<p><strong>Conclusions</strong></p>

<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.</p>
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