A Comparison of Crotalinae (Pit Viper) Equine Immune F(ab)2 Antivenom (Anavip) and Crotalidae Polyvalent Immune Fab, Ovine Antivenom (CroFab) in the Treatment of Pit Viper Envenomation

Blood Coagulation Disorders Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00868309
• Other study ID #: AN-03/02
• Secondary ID: AN-03/02
• Status: Completed
• Phase: Phase 2
• First received: November 6, 2008
• Last updated: April 3, 2009
• Start date: January 2005
• Est. completion date: February 2007

Study information

• Verified date: April 2009
• Source: Instituto Bioclon S.A. de C.V.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: February 2007
• Est. primary completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• Hemostatic Disorders
• Snake Bite
• Snake Bites

Intervention

Biological:
• Antivenin Crotalinae (pit viper) equine immune F(ab)2
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
CroFab, 5 vials Intravenous (IV) every 2 hours until initial control has been achieved; then 3 maintenance doses of 2 vials every 6 hrs

Locations

Country	Name	City	State
United States	Tucson snakebite investigational site	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Instituto Bioclon S.A. de C.V.	University of Arizona

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Detection of Plasma Venom Levels During the Post Acute Treatment Period.		Follow up after Maintenance doses were completed. Two Weeks.	Yes
Secondary	Thrombocytopenia During Follow up Period. Two Weeks.		Follow up after maintenance dose	Yes