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

This study has been completed.
Sponsor:
Collaborator:
University of Arizona
Information provided by:
Instituto Bioclon S.A. de C.V.
ClinicalTrials.gov Identifier:
NCT00868309
First received: November 6, 2008
Last updated: April 3, 2009
Last verified: April 2009
  Purpose

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 Intervention Phase
Snake Bite
Blood Coagulation Disorders
Biological: Antivenin Crotalinae (pit viper) equine immune F(ab)2
Biological: CroFab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Instituto Bioclon S.A. de C.V.:

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

Secondary Outcome Measures:
  • Thrombocytopenia During Follow up Period. Two Weeks. [ Time Frame: Follow up after maintenance dose ] [ Designated as safety issue: Yes ]

Enrollment: 12
Study Start Date: January 2005
Study Completion Date: February 2007
Primary Completion Date: August 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anavip 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
Other Name: Anavip
Active Comparator: CroFab 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
Other Name: CroFab

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00868309

Locations
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
Investigators
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
  More Information

No publications provided

Responsible Party: Walter García Ubbelohde. MD/ Clinical Research Manager, Instituto Bioclon S.A. de C.V.
ClinicalTrials.gov Identifier: NCT00868309     History of Changes
Other Study ID Numbers: AN-03/02, AN-03/02
Study First Received: November 6, 2008
Results First Received: November 6, 2008
Last Updated: April 3, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Instituto Bioclon S.A. de C.V.:
Snake Bite
Venom and antivenom kinetics

Additional relevant MeSH terms:
Blood Coagulation Disorders
Hemostatic Disorders
Snake Bites
Hematologic Diseases
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders
Bites and Stings
Poisoning
Chemically-Induced Disorders
Wounds and Injuries
Antivenins
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014