- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00868309
A Comparison of Crotalinae Equine Immune F(ab)2 Antivenom (Anavip) and Crotalidae Polyvalent Immune Fab,
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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Arizona
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Tucson, Arizona, United States, 85724
- Tucson snakebite investigational site
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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
|
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 Names:
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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.
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CroFab, 5 vials Intravenous (IV) every 2 hours until initial control has been achieved; then 3 maintenance doses of 2 vials every 6 hrs
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Detection of Plasma Venom Levels During the Post Acute Treatment Period.
Time Frame: Follow up after Maintenance doses were completed. Two Weeks.
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Follow up after Maintenance doses were completed. Two Weeks.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
>50,000 Platelets/mm3
Time Frame: Follow up after maintenance dose
|
Thrombocytopenia during follow up period.
Two weeks
|
Follow up after maintenance dose
|
Collaborators and Investigators
Sponsor
Collaborators
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
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- AN-03/02 (Other Identifier: Bioclon)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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