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

NCT ID: NCT00868309

Last Updated: 2016-04-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-31
• Study Completion Date: 2007-02-28

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.

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.

Conditions

Snake Bite; Blood Coagulation Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Anavip

Intervention Type: BIOLOGICAL

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

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.

Group Type: ACTIVE_COMPARATOR

CroFab

Intervention Type: BIOLOGICAL

CroFab, 5 vials Intravenous (IV) every 2 hours until initial control has been achieved; then 3 maintenance doses of 2 vials every 6 hrs

Interventions

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

Intervention Type: 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

Intervention Type: BIOLOGICAL

Other Intervention Names

Antivenin Crotalinae (pit viper) equine immune F(ab)2

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Arizona

OTHER

Sponsor Role: collaborator

Instituto Bioclon S.A. de C.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Walter García, MD

Role: STUDY_DIRECTOR

Instituto Bioclon

Leslie Boyer, MD

Role: PRINCIPAL_INVESTIGATOR

University of Arizona

Alejandro Alagón, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Instituto de Biotecnología UNAM

Locations

Tucson snakebite investigational site

Tucson, Arizona, United States

Countries

United States

Other Identifiers

AN-03/02

Identifier Type: OTHER

Identifier Source: secondary_id

AN-03/02

Identifier Type: -

Identifier Source: org_study_id