Phase 3 Multicenter Comparative Study to Confirm Safety and Effectiveness of the F(ab)2 Antivenom Anavip.

Study Overview
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Brief Summary
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The purpose of this study is to establish if F(ab)2 antivenom (Anavip) is safe for crotalinae envenomation. Confirm its effectiveness in preventing the occurrence of delayed coagulopathies and compare the safety and efficacy with Fab antivenom (CroFab) in patients with Crotalinae envenomation.

Detailed Description
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Fewer than 200,000 crotaline envenomations occur annually in the US.Crotaline venoms contain a broad variety of toxins, venom variability and injection quantity among individual snakes and across species result in broadly variable patient presentations. Clinical consequences of crotaline envenomation include local and systemic effects, both of which may progress for hours to days.The best studied systemic consequence is coagulopathy, which may in its complexity mimic disseminated intravascular coagulation. Platelet and clotting disorders respond rapidly to administration of polyvalent antivenom. Crotaline viper envenomation in the United States is treated with one of two licensed products: Wyeth Antivenin (Crotalidae) Polyvalent (Polyvalent), or CroFab® (antivenin Crotalidae polyvalent immune Fab, ovine). In recent years, both of these products have been in critically short supply. Use of Wyeth Polyvalent has been associated with a greater than 75% incidence of adverse reactions, including acute type 1 and delayed type 2 immune reactions.These phenomena are an inherent risk in the use of whole immunoglobulin. CroFab´s low molecular weight creates a pharmacokinetic mismatch with crotaline venom which leds to a recurrent venom effects. Anavip is pharmacologically and pharmacokinetically different.Because of the elimination of the Fc portion of the immunoglobulin molecule, Anavip is expected to produce far fewer adverse reactions than seen with whole immunoglobulin antivenoms and unlike Fab molecules, F(ab)2 molecules exceed the size threshold for renal clearance and thus are expected to remain in circulation for a significantly longer time and substantially reduce the incidence of recurrent coagulopathy.

Official Title
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A Comparison of Anavip® and CroFab® in the Treatment of Patients With Crotalinae Envenomation: A Randomized, Prospective, Blinded, Controlled, Comparative, Multicenter Study

Conditions
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Snake Bite

Intervention / Treatment
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* Biological: Crotalinae (pit viper) equine immune F(ab)2
* Biological: Crotalinae (pit viper) equine immune F(ab)2
* Biological: Crotalidae Polyvalent Immune Fab, ovine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women 2 to 80 years of age Presenting for emergency treatment of pit viper bite Informed consent document read and signed by patient (or parent/legal guardian) Exclusion Criteria: Current use of any antivenom, or use within the last month Current participation in a clinical drug study, or participation within the last month Positive urine or blood pregnancy test at screening Breast-feeding Allergy to horse serum, sheep serum, or papaya Underlying medical conditions that significantly alter platelet count or fibrinogen; thrombocytopenia, hemophilia, familial dysfibrinogenemia, leukemia Use of any medication expected to affect platelet count, coagulation factors or fibrinogen: chemotherapeutic agents, warfarin, heparin No clinical indications of snake bite requiring antivenom for treatment

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Anavip with Anavip Maintenance Therapy | Biological: Crotalinae (pit viper) equine immune F(ab)2<br>* Anavip with Anavip Maintenance Therapy<br>* Other names: Anavip;|
| Experimental: Group 2<br>Anavip with Placebo Maintenance Therapy | Biological: Crotalinae (pit viper) equine immune F(ab)2<br>* Anavip with Placebo Maintenance Therapy<br>* Other names: Anavip;|
| Active Comparator: Group 3<br>CroFab with CroFab Maintenance Therapy | Biological: Crotalidae Polyvalent Immune Fab, ovine<br>* CroFab with CroFab Maintenance Therapy<br>* Other names: CroFab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of patients experiencing coagulopathy during the follow-up phase of the study. Absolute Platelet levels < 150,000/mm3. Absolute Fibrinogen levels < 150 mg/dL. Clinical coagulopathy requiring additional antivenom. |  | Study Day 5 (±/- 1 day), Study Day 8 (±/- 1 day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison between groups of: Percentage of patients who experience venonemia. Absolute platelet level measured Lowest absolute platelet level measured Absolute fibrinogen level Lowest absolute fibrinogen level |  | Study Day 5 (+/- 1 day) and Study Day 8 (+/- 1 day) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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snake bite, antivenin treatment