Adjunctive Varespladib after antivenom administration for snakebite: A phase II randomized clinical trial

Background 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. Methods and findings 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. Conclusions 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.

Authors

Institutions

Publication Details

Journal
PLoS neglected tropical diseases
Published
2026-09-21
DOI
https://doi.org/10.1371/journal.pntd.0014736
Primary Topic
Venomous Animal Envenomation and Studies
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
article

Adjunctive Varespladib after antivenom administration for snakebite: A phase II randomized clinical trial

Rebecca W. Carter, Suresh Selvam, Samuel Francis, Shawn M. Varney et al.
PLoS neglected tropical diseases
Venomous Animal Envenomation and Studies
article

Adjunctive Varespladib after antivenom administration for snakebite: A phase II randomized clinical trial

Rebecca W. Carter, Suresh Selvam, Samuel Francis, Shawn M. Varney, Medhavi Gautam, Suneil Agrawal, Chitta R. Mohanty, Peter Akpunonu, Matthew R. Lewin, A Goel, Timothy F. Platts‐Mills, Andrew Micciche, Norman L. Beatty, Harish Kumar, Adiel Aizenberg, Ashish Bhalla, Suraj C. Oomman, Anne-Michelle Ruha, Manu Ayyan S, Janet T. Wittes, Ginger Boatright, Travis Deuson, Sarah Watkins, Justin Arnold, Eileen Shu, Chanaveerappa Bammigatti, Charles J. Gerardo, Stephen P. Samuel, Farshad M. Shirazi, Surendra Kumar, Badal K. Sahu, Madhu Kumar R, Rylee S. Bledsoe
article en

Abstract

Background 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. Methods and findings 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. Conclusions 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.

PLoS neglected tropical diseasesVol. 20(9)
Twitter (United States) (US), Texas Tech University (US), University of Arizona (US), University of Kentucky (US), Deloitte (United States) (US), Nil Ratan Sircar Medical College and Hospital (IN), The University of Texas at San Antonio Health Science Center (US), Antelope Valley Hospital (US), Sardar Patel Medical College (IN), Santa Clara Valley Medical Center (US), Tampa General Hospital (US), California Academy of Sciences (US), University of Florida (US), King George Hospital (GB), Valley Medical Center (US), Washington Poison Center (US), Desert Regional Medical Center (US), Banner - University Medical Center Tucson (US), Marien Hospital Witten (DE), Mysore Medical College (IN), Duke University Hospital (US), Sardar Patel University (IN), Jawaharlal Institute of Post Graduate Medical Education and Research (IN), All India Institute of Medical Sciences (IN), Texas Tech University Health Sciences Center (US)
Openalex Percentile: Top 12%
Venomous Animal Envenomation and Studies
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.