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Comparison of F(ab')2 versus Fab antivenom for pit viper envenomation: a prospective, blinded, multicenter, randomized clinical trial.
Clin Toxicol (Phila). 2015 Jan; 53(1):37-45.CT

Abstract

BACKGROUND

Crotalidae Polyvalent Immune Fab (Ovine) has been the only antivenom commercially available in the US since 2007 for treatment of Crotalinae envenomation. Late coagulopathy can occur or recur after clearance of Fab antivenom, often after hospital discharge, lasting in some cases more than 2 weeks. There have been serious, even fatal, bleeding complications associated with recurrence phenomena. Frequent follow-up is required, and additional intervention or hospitalization is often necessary. F(ab')2 immunoglobulin derivatives have longer plasma half life than do Fab. We hypothesized that F(ab')2 antivenom would be superior to Fab in the prevention of late coagulopathy following treatment of patients with Crotalinae envenomation.

METHODS

We conducted a prospective, double-blind, randomized clinical trial, comparing late coagulopathy in snakebitten patients treated with F(ab')2 with maintenance doses [F(ab')2/F(ab')2], or F(ab')2 with placebo maintenance doses [F(ab')2/placebo], versus Fab with maintenance doses [Fab/Fab]. The primary efficacy endpoint was coagulopathy (platelet count < 150 K/mm(3), fibrinogen level < 150 mg/dL) between end of maintenance dosing and day 8.

RESULTS

121 patients were randomized at 18 clinical sites and received at least one dose of study drug. 114 completed the study. Of these, 11/37 (29.7%) in the Fab/Fab cohort experienced late coagulopathy versus 4/39 (10.3%, p < 0.05) in the F(ab')2/F(ab')2 cohort and 2/38 (5.3%, p < 0.05) in the F(ab')2/placebo cohort. The lowest heterologous protein exposure was with F(ab')2/placebo. No serious adverse events were related to study drug. In each study arm, one patient experienced an acute serum reaction and one experienced serum sickness.

CONCLUSIONS

In this study, management of coagulopathic Crotalinae envenomation with longer-half-life F(ab')2 antivenom, with or without maintenance dosing, reduced the risk of subacute coagulopathy and bleeding following treatment of envenomation.

Authors+Show Affiliations

East Carolina University Brody School of Medicine/Vidant Medical Center , Greenville, NC , USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

25361165

Citation

Bush, Sean P., et al. "Comparison of F(ab')2 Versus Fab Antivenom for Pit Viper Envenomation: a Prospective, Blinded, Multicenter, Randomized Clinical Trial." Clinical Toxicology (Philadelphia, Pa.), vol. 53, no. 1, 2015, pp. 37-45.
Bush SP, Ruha AM, Seifert SA, et al. Comparison of F(ab')2 versus Fab antivenom for pit viper envenomation: a prospective, blinded, multicenter, randomized clinical trial. Clin Toxicol (Phila). 2015;53(1):37-45.
Bush, S. P., Ruha, A. M., Seifert, S. A., Morgan, D. L., Lewis, B. J., Arnold, T. C., Clark, R. F., Meggs, W. J., Toschlog, E. A., Borron, S. W., Figge, G. R., Sollee, D. R., Shirazi, F. M., Wolk, R., de Chazal, I., Quan, D., García-Ubbelohde, W., Alagón, A., Gerkin, R. D., & Boyer, L. V. (2015). Comparison of F(ab')2 versus Fab antivenom for pit viper envenomation: a prospective, blinded, multicenter, randomized clinical trial. Clinical Toxicology (Philadelphia, Pa.), 53(1), 37-45. https://doi.org/10.3109/15563650.2014.974263
Bush SP, et al. Comparison of F(ab')2 Versus Fab Antivenom for Pit Viper Envenomation: a Prospective, Blinded, Multicenter, Randomized Clinical Trial. Clin Toxicol (Phila). 2015;53(1):37-45. PubMed PMID: 25361165.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparison of F(ab')2 versus Fab antivenom for pit viper envenomation: a prospective, blinded, multicenter, randomized clinical trial. AU - Bush,Sean P, AU - Ruha,Anne-Michelle, AU - Seifert,Steven A, AU - Morgan,David L, AU - Lewis,Brandon J, AU - Arnold,Thomas C, AU - Clark,Richard F, AU - Meggs,William J, AU - Toschlog,Eric A, AU - Borron,Stephen W, AU - Figge,Gary R, AU - Sollee,Dawn R, AU - Shirazi,Farshad M, AU - Wolk,Robert, AU - de Chazal,Ives, AU - Quan,Dan, AU - García-Ubbelohde,Walter, AU - Alagón,Alejandro, AU - Gerkin,Richard D, AU - Boyer,Leslie V, Y1 - 2014/10/31/ PY - 2014/11/1/entrez PY - 2014/11/2/pubmed PY - 2015/3/3/medline KW - Antivenins KW - Snakes KW - Toxinology SP - 37 EP - 45 JF - Clinical toxicology (Philadelphia, Pa.) JO - Clin Toxicol (Phila) VL - 53 IS - 1 N2 - BACKGROUND: Crotalidae Polyvalent Immune Fab (Ovine) has been the only antivenom commercially available in the US since 2007 for treatment of Crotalinae envenomation. Late coagulopathy can occur or recur after clearance of Fab antivenom, often after hospital discharge, lasting in some cases more than 2 weeks. There have been serious, even fatal, bleeding complications associated with recurrence phenomena. Frequent follow-up is required, and additional intervention or hospitalization is often necessary. F(ab')2 immunoglobulin derivatives have longer plasma half life than do Fab. We hypothesized that F(ab')2 antivenom would be superior to Fab in the prevention of late coagulopathy following treatment of patients with Crotalinae envenomation. METHODS: We conducted a prospective, double-blind, randomized clinical trial, comparing late coagulopathy in snakebitten patients treated with F(ab')2 with maintenance doses [F(ab')2/F(ab')2], or F(ab')2 with placebo maintenance doses [F(ab')2/placebo], versus Fab with maintenance doses [Fab/Fab]. The primary efficacy endpoint was coagulopathy (platelet count < 150 K/mm(3), fibrinogen level < 150 mg/dL) between end of maintenance dosing and day 8. RESULTS: 121 patients were randomized at 18 clinical sites and received at least one dose of study drug. 114 completed the study. Of these, 11/37 (29.7%) in the Fab/Fab cohort experienced late coagulopathy versus 4/39 (10.3%, p < 0.05) in the F(ab')2/F(ab')2 cohort and 2/38 (5.3%, p < 0.05) in the F(ab')2/placebo cohort. The lowest heterologous protein exposure was with F(ab')2/placebo. No serious adverse events were related to study drug. In each study arm, one patient experienced an acute serum reaction and one experienced serum sickness. CONCLUSIONS: In this study, management of coagulopathic Crotalinae envenomation with longer-half-life F(ab')2 antivenom, with or without maintenance dosing, reduced the risk of subacute coagulopathy and bleeding following treatment of envenomation. SN - 1556-9519 UR - https://www.unboundmedicine.com/medline/citation/25361165/Comparison_of_F_ab'_2_versus_Fab_antivenom_for_pit_viper_envenomation:_a_prospective_blinded_multicenter_randomized_clinical_trial_ L2 - https://www.tandfonline.com/doi/full/10.3109/15563650.2014.974263 DB - PRIME DP - Unbound Medicine ER -