A Comparison of Crotalinae Equine Immune F(ab)2 Antivenom (Anavip) and Crotalidae Polyvalent Immune Fab,
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| ClinicalTrials.gov Identifier: NCT00868309 |
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Recruitment Status :
Completed
First Posted : March 24, 2009
Results First Posted : March 24, 2009
Last Update Posted : April 18, 2016
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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 |
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 : | 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 |
| Arm | Intervention/treatment |
|---|---|
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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
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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 |
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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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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 |
- Detection of Plasma Venom Levels During the Post Acute Treatment Period. [ Time Frame: Follow up after Maintenance doses were completed. Two Weeks. ]
- >50,000 Platelets/mm3 [ Time Frame: Follow up after maintenance dose ]Thrombocytopenia during follow up period. Two weeks
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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
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
| United States, Arizona | |
| Tucson snakebite investigational site | |
| Tucson, Arizona, United States, 85724 | |
| 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 |
| Responsible Party: | Instituto Bioclon S.A. de C.V. |
| ClinicalTrials.gov Identifier: | NCT00868309 History of Changes |
| 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.:
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Snake Bite Venom and antivenom kinetics |
Additional relevant MeSH terms:
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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 |