A Comparison of Crotalinae Equine Immune F(ab)2 Antivenom (Anavip) and Crotalidae Polyvalent Immune Fab,
Condition: Snake Bite; Blood Coagulation Disorders
MeSH terms: Hemostatic Disorders; Blood Coagulation Disorders; Snake Bites
Study type: Interventional
Phase: Phase 2

Summary: 
      This phase II study was a prospective, randomized, open-label, multi-center study in the
      United States, involving patients from 18 to 70 years of age, comparing Anavip (Antivenin
      Crotalinae [pit viper] equine immune F(ab)2; Instituto Bioclon, Mexico City, Mexico) against
      CroFab (Protherics Inc., Nashville, Tennessee), the only currently approved product for
      treatment of Crotalinae (pit viper) envenomation in the US.

      The study was designed to evaluate the hypothesis that lasting correction of snakebite
      induced thrombocytopenia and hypofibrinogenemia are possible following correction with F(ab)2
      antivenom, by analyzing in detail the relationships among platelet count, fibrinogen, venom
      levels, and antivenom levels in subjects presenting with thrombocytopenia following crotaline
      viper envenomation. In the study we expected to see a fall in platelet count following Fab
      treatment, commensurate with that reported in the past. We hypothesized that following F(ab)2
      treatment there would be a slower drop in post-treatment platelet counts, with a relatively
      higher platelet count at any given point in the follow-up period. We further hypothesized
      that an initial rise and later fall in platelet count would correspond with rise and fall in
      antivenom levels, and would be mirrored by concurrent drop and rise in levels of unbound
      circulating venom.
    

Detailed description: 
      The overall objective of this Phase 2 open-label comparative study was to demonstrate that
      the F(ab)2 antivenom Anavip has significantly longer plasma persistence than does Fab, and
      that this is associated with a slower rise in venom levels and slower decline in platelet
      count and fibrinogen following hospital discharge of envenomated subjects. The effectiveness
      of F(ab)2 in preventing the recurrence of coagulopathies after the subject's discharge from
      hospital will indicate that, inherently, F(ab)2 antivenom has an improved safety profile
      relative to the Fab antivenom CroFab in treating envenomation by crotaline vipers.

      Each subject was assessed for quantitative serum venom levels. Relatively few historical data
      exist to support the use of venom levels as a surrogate endpoint in envenomation. However,
      changes in venom levels have been correlated with coagulopathic effects, during both the
      acute phase of venom toxicity and the post treatment period of recurrent venom effect.
      Validation of this surrogate endpoint via correlation of venom effect with platelet count and
      fibrinogen level in this phase II study is intended to support future studies.

      The secondary endpoints were the determination of coagulation abnormalities during the follow
      up period.
    

Intervention name(s): Anavip; CroFab
Intervention type(s): Biological; Biological
Intervention description(s): Anavip, 10 vials Intravenous (IV) every 2 hours until initial control has been achieved; then 3 maintenance doses of 4 vials every 6 hrs; CroFab, 5 vials Intravenous (IV) every 2 hours until initial control has been achieved; then 3 maintenance doses of 2 vials every 6 hrs
Other intervention name(s): Antivenin Crotalinae (pit viper) equine immune F(ab)2
Intervention MeSH terms: Antivenins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Snake Bite; Venom and antivenom kinetics