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A Comparison of Crotalinae Equine Immune F(ab)2 Antivenom (Anavip) and Crotalidae Polyvalent Immune Fab,

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ClinicalTrials.gov Identifier: NCT00868309
Recruitment Status : Completed
First Posted : March 24, 2009
Results First Posted : March 24, 2009
Last Update Posted : April 18, 2016
University of Arizona
Information provided by (Responsible Party):
Instituto Bioclon S.A. de C.V.

Brief 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.

Condition or disease Intervention/treatment Phase
Snake Bite Blood Coagulation Disorders Biological: Anavip Biological: CroFab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : January 2005
Actual Primary Completion Date : August 2006
Actual Study Completion Date : February 2007

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Anavip
The initial dose of study drug was administered in a total volume of 500 mL (initial doses only) IV over 30 minutes for Anavip
Biological: Anavip
Anavip, 10 vials Intravenous (IV) every 2 hours until initial control has been achieved; then 3 maintenance doses of 4 vials every 6 hrs
Other Name: Antivenin Crotalinae (pit viper) equine immune F(ab)2

Active Comparator: CroFab
The initial dose of study drug was administered in a total volume of 500 mL (initial doses only) IV over 60 minutes for CroFab, or as permitted by IV access.
Biological: 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

Primary Outcome Measures :
  1. Detection of Plasma Venom Levels During the Post Acute Treatment Period. [ Time Frame: Follow up after Maintenance doses were completed. Two Weeks. ]

Secondary Outcome Measures :
  1. >50,000 Platelets/mm3 [ Time Frame: Follow up after maintenance dose ]
    Thrombocytopenia during follow up period. Two weeks

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00868309

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United States, Arizona
Tucson snakebite investigational site
Tucson, Arizona, United States, 85724
Sponsors and Collaborators
Instituto Bioclon S.A. de C.V.
University of Arizona
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Study Director: Walter García, MD Instituto Bioclon
Principal Investigator: Leslie Boyer, MD University of Arizona
Principal Investigator: Alejandro Alagón, MD, PhD Instituto de Biotecnología UNAM
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Responsible Party: Instituto Bioclon S.A. de C.V.
ClinicalTrials.gov Identifier: NCT00868309    
Other Study ID Numbers: AN-03/02
AN-03/02 ( Other Identifier: Bioclon )
First Posted: March 24, 2009    Key Record Dates
Results First Posted: March 24, 2009
Last Update Posted: April 18, 2016
Last Verified: March 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Instituto Bioclon S.A. de C.V.:
Snake Bite
Venom and antivenom kinetics
Additional relevant MeSH terms:
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Hemostatic Disorders
Blood Coagulation Disorders
Snake Bites
Hematologic Diseases
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders
Bites and Stings
Chemically-Induced Disorders
Wounds and Injuries
Immunologic Factors
Physiological Effects of Drugs