Phase 3 Multicenter Comparative Study to Confirm Safety and Effectiveness of the F(ab)2 Antivenom Anavip.
- Conditions
- Snake Bite
- Interventions
- Biological: Crotalinae (pit viper) equine immune F(ab)2Biological: Crotalidae Polyvalent Immune Fab, ovine
- Registration Number
- NCT00636116
- Lead Sponsor
- Instituto Bioclon S.A. de C.V.
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 121
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1 Crotalinae (pit viper) equine immune F(ab)2 Anavip with Anavip Maintenance Therapy Group 2 Crotalinae (pit viper) equine immune F(ab)2 Anavip with Placebo Maintenance Therapy Group 3 Crotalidae Polyvalent Immune Fab, ovine CroFab with CroFab Maintenance Therapy
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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)
Trial Locations
- Locations (18)
The Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
University Physicians Hospital
🇺🇸Tucson, Arizona, United States
University Medical Center
🇺🇸Tucson, Arizona, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
LSU Health Sciences Center, Lousiana Poison Control Center
🇺🇸Shreveport, Louisiana, United States
Pitt County Memorial Hospital
🇺🇸Greenville, North Carolina, United States
Florida Poison Information Center
🇺🇸Jacksonsville, Florida, United States
Sarasota Memorial Hospital
🇺🇸Sarasota, Florida, United States
Tucson Medical Center
🇺🇸Tucson, Arizona, United States
West Texas Regional Poison Center at Thomason Hospital
🇺🇸El Paso, Texas, United States
St. Joseph Regional Health Center
🇺🇸Bryan, Texas, United States
Scott and White Memorial Hospital
🇺🇸Temple, Texas, United States
Maricopa Integrated Health System
🇺🇸Phoenix, Arizona, United States
Banner Good Samaritan Medical Center
🇺🇸Phoenix, Arizona, United States
Northwest Medical Center
🇺🇸Phoenix, Arizona, United States
University of California San Diego
🇺🇸San Diego, California, United States
Rady Children's Hospital
🇺🇸San Diego, California, United States
The University of New Mexico Hospital
🇺🇸Albuquerque, New Mexico, United States