title: Comparison of F(ab')2 versus Fab antivenom for pit viper envenomation: a prospective, blinded, multicenter, randomized clinical trial.
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.affiliation: East Carolina University Brody School of Medicine/Vidant Medical Center , Greenville, NC , USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Bush
authors.forename: Anne-Michelle
authors.initials: AM
authors.lastname: Ruha
authors.forename: Steven A
authors.initials: SA
authors.lastname: Seifert
authors.forename: David L
authors.initials: DL
authors.lastname: Morgan
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Lewis
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Arnold
authors.forename: Richard F
authors.initials: RF
authors.lastname: Clark
authors.forename: William J
authors.initials: WJ
authors.lastname: Meggs
authors.forename: Eric A
authors.initials: EA
authors.lastname: Toschlog
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Borron
authors.forename: Gary R
authors.initials: GR
authors.lastname: Figge
authors.forename: Dawn R
authors.initials: DR
authors.lastname: Sollee
authors.forename: Farshad M
authors.initials: FM
authors.lastname: Shirazi
authors.forename: Robert
authors.initials: R
authors.lastname: Wolk
authors.forename: Ives
authors.initials: I
authors.lastname: de Chazal
authors.forename: Dan
authors.initials: D
authors.lastname: Quan
authors.forename: Walter
authors.initials: W
authors.lastname: García-Ubbelohde
authors.forename: Alejandro
authors.initials: A
authors.lastname: Alagón
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gerkin
authors.forename: Leslie V
authors.initials: LV
authors.lastname: Boyer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000997:Antivenins / Q000494:pharmacology*; D001778:Blood Coagulation Disorders / Q000188:drug therapy / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D003435:Crotalid Venoms / Q000633:toxicity*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011446:Prospective Studies; D012909:Snake Bites / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome; D017819:Viperidae; D055815:Young Adult
chemical_list: D000997:Antivenins; D003435:Crotalid Venoms; C431183:Crotalidae Polyvalent immune Fab; D007140:Immunoglobulin Fab Fragments
keywords: Antivenins; Snakes; Toxinology