NACCT Abstracts 2016

Clinical Toxicology

ISSN: 1556-3650 (Print) 1556-9519 (Online) Journal homepage: http://www.tandfonline.com/loi/ictx20

NACCT Abstracts 2016 To cite this article: (2016) NACCT Abstracts 2016, Clinical Toxicology, 54:8, 659-811, DOI: 10.1080/15563650.2016.1197486 To link to this article: http://dx.doi.org/10.1080/15563650.2016.1197486

Published online: 18 Jul 2016.

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Date: 27 February 2017, At: 13:30

CLINICAL TOXICOLOGY, 2016 VOL. 54, NO. 8, 659–811 http://dx.doi.org/10.1080/15563650.2016.1197486

NACCT Abstracts 2016

1. A Phase III Clinical Trial of AnalatroV [Antivenin Latrodectus (Black Widow) Equine Immune F(ab’)2] in Patients with Systemic Latrodectism R

R. C. Darta, Kennon Heardb, S. P. Bushc, T. C. Arnoldd, M. E. Suttere, D. Campagnef, Christopher Holstegeg, Steven Seiferth, D. Quani, Stephen W. Borronj, D. A. Meurerk and V. E. Andersonl a Rocky Mountain Poison and Drug Center, Denver Hospital Health Authority; bUniversity of Colorado Denver - Anschutz; cEast Carolina University Brody School of Medicine/Vidant Medical Center; d Louisiana State University Health Sciences Center – Shreveport; e University of California, Davis, Department of Emergency Medicine; f University of California, San Francisco, Fresno, CA; gUniversity of Virginia School of Medicine; hNew Mexico Poison and Drug Information Center, University of New Mexico Health Sciences Center; iMaricopa Integrated Health System, Department of Emergency Medicine; jTexas Tech University Health Sciences Center; k University of Florida College of Medicine, Department of Emergency Medicine; lRocky Mountain Poison and Drug Center Denver Health

Background: There are 5 species of widow spiders (Latrodectus) in North America, with 1692 bites reported to US Poison Centers in 2014. Therapy for latrodectism in the US may include opioid analgesics, benzodiazepines, muscle relaxants or a currently approved equine based antivenom (AV), which carries a perceived increased risk of hypersensitivity due to its whole IgG preparation. The objective of this study is to determine the safety and efficacy of a highly purified equine based F(ab’)2 AV (AnalatroV) for the treatment of pain associated with latrodectism. Methods: A Phase III, randomized, double blind, placebo controlled trial was conducted at 16 sites across the US. Patients were randomized to 1 of 2 treatment groups: F(ab’)2 AV or saline placebo. Patients with moderate to severe pain intensity measured using the visual analog scale (VAS) were enrolled and treated with up to 2 doses of study drug. Pain intensity was assessed at baseline and every 30 minutes thereafter, for up to 150 minutes. Patients with moderate to severe pain or those who failed to achieve a clinically significant reduction in pain after dose 1 received a 2nd dose. The primary outcome measure was treatment failure, which was defined as failure to achieve and maintain clinically significant reduction in pain for 48 hours posttreatment. The proportion of treatment failures in each group was compared using a 1-sided Chi-squared test. Pain intensity differences (PID) over time were assessed using change in VAS scores relative to baseline at each post baseline time point using a mixed effects model. The summed PID (SPID) was computed for each subject using the area under the curve trapezoidal method. Adverse events (AEs) were recorded through day 17. Results: 60 patients were treated (29 AV:31 placebo). The mean age was 39 years and 66% were male. There were 15 treatment failures in the AV group and 24 in the placebo group R

ß 2016 Informa UK Limited, trading as Taylor & Francis Group

Time (mins) 30 60 90 120 150

Mean Difference in PID (AV- Placebo)

p-value

10.9 14.6 16.6 20.2 21.2

0.1244 0.0401 0.0195 0.0047 0.0029

(p ¼ 0.0185). The mean difference in PID observed between groups was significant at 60, 90, 120, and 150 minutes post baseline (Table). The mean SPID was significantly greater for the AV group (p ¼ 0.0135). The frequency and types of AEs reported were similar between groups. No deaths or serious drug related AEs were reported. Conclusions: This equine based F(ab’)2 AV was effective at reducing moderate to severe pain caused by latrodectism. No serious safety concerns were identified in this study. KEYWORDS Black widow; antivenom; latrodectism [email protected]

2. A randomised controlled trial of low dose antivenom and fresh frozen plasma versus high dose antivenom for coagulopathy in Russell’s viper envenoming Geoffrey Isbistera, Kalana Maduwageb, Shaluka Jayamannec, Fahim Mohamedd, Andrew Dawsone, Indika Gawarammanaf, Janaka De Silvag, David Lallooh and Nicholas Buckleyi a

University of Newcastle; bUniversity of Peradeniya; cUniversity of Kelaniya; dSouth Asian Clinical Toxicology Research Collaboration; e University of Sydney; fUniversity of Peradeniya; gUniversity of Kelaniya; hLiverpool University; iUniversity of Sydney Objectives: Russell’s viper (Daboia russelii) envenoming is a major health issue in South Asia. Russell’s viper envenoming causes venom induced consumption coagulopathy (VICC), which takes 24-48h to resolve. We investigated the effect of fresh frozen plasma (FFP) and two different antivenom doses in correcting the coagulopathy from Russell’s viper envenoming, post-antivenom. Methods: We undertook an open-label randomised controlled trial at two Sri Lankan hospitals in patients with VICC, comparing 20 vials of polyvalent antivenom (high dose) to 10 vials of antivenom (low dose) with 4U FFP. Patients (>15yr) were recruited if they had a Russell’s viper bite and positive whole blood clotting test. Patients were allocated in a 1:1 randomisation. The primary outcome was the proportion with an INR 1000 u/L) developed in 2 out of 65 of the two-stage regimen and and 2 out of the FDA labeled regimen (Pearson chi2 ¼ 0.004 and P value ¼0.9). All hepatotoxicity have resolved, no patient had liver transplant or died. There were a total of 27 NAC administrations

665

errors. 4 errors in the two-stage regimen (2 interruption errors, 1 dose related error and 1 missing loading dose) and 23 errors in the FDA labeled regimen (15 interruption errors, 6 dose related errors, 1 missing loading dose and 1 infusion stopped before 21 hours), with statistically significant difference P value