A Comparison of Crotalinae Equine Immune F(ab)2 Antivenom (Anavip) and Crotalidae Polyvalent Immune Fab,
| Status: | Completed |
|---|---|
| Conditions: | Infectious Disease, Hematology |
| Therapuetic Areas: | Hematology, Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - 70 |
| Updated: | 4/21/2016 |
| Start Date: | January 2005 |
| End Date: | February 2007 |
A Comparison of Anavip and CroFab in the Treatment of Subjects With Crotalinae (Pit Viper) Envenomation: A Randomized, Prospective, Open-Label, Controlled, Comparative, Multicenter Study
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.
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.
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.
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.
Inclusion Criteria:
- men and women 18 to 70 years of age
- presenting for emergency treatment of pit viper bite
- informed consent document read and signed by subject
Exclusion Criteria:
- allergy to horse serum, sheep serum, or papaya
- current use of any antivenom, or use within the last month
- current participation in a clinical drug study, or participation within the last
month
- pregnancy or breast-feeding
- underlying medical conditions that significantly alter blood coagulation:
thrombocytopenia, hemophilia, familial dysfibrinogenemia, leukemia, recent ingestion
of superwarfarin compounds (rat poison)
- use of any medication expected to affect platelet count, coagulation factors, or
fibrinogen: chemotherapeutic agents, warfarin, heparin, aspirin
- No clinical indications of snake bite envenomation
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