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

Condition(s) targeted: Snake Bite

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

Phase: Phase 3

Status: Recruiting

Sponsored by: Instituto Bioclon S.A. de C.V.

Official(s) and/or principal investigator(s):
Walter García Ubbelohde, MD, Study Director, Affiliation: Instituto Bioclon

Overall contact:
Walter García, MD, Phone: (5255)54883700, Ext: 3785, Email: wgarcia@silanes.com.mx

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: 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.

Secondary outcome: 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

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.

Minimum age: 2 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

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

Walter García, MD, Phone: (5255)54883700, Ext: 3785, Email: wgarcia@silanes.com.mx

Northwest Medical Center, Phoenix, Arizona 85741, United States; Terminated

Banner Good Samaritan Medical Center, Phoenix, Arizona 85006, United States; Recruiting

Maricopa Integrated Health System, Phoenix, Arizona 85008, United States; Active, not recruiting

University Physicians Hospital, Tucson, Arizona 85713, United States; Terminated

Tucson Medical Center, Tucson, Arizona 85712, United States; Active, not recruiting

University Medical Center, Tucson, Arizona 85721, United States; Terminated

Loma Linda University Medical Center, Loma Linda, California 92354, United States; Recruiting

Rady Children's Hospital, San Diego, California 92123, United States; Recruiting

University of California San Diego, San Diego, California 92103, United States; Active, not recruiting

Florida Poison Information Center, Jacksonsville, Florida 32209, United States; Active, not recruiting

Sarasota Memorial Hospital, Sarasota, Florida 34239, United States; Active, not recruiting

LSU Health Sciences Center, Lousiana Poison Control Center, Shreveport, Louisiana 71103, United States; Recruiting

The Children's Mercy Hospital, Kansas City, Missouri 64108, United States; Completed

The University of New Mexico Hospital, Albuquerque, New Mexico 87106, United States; Recruiting

Pitt County Memorial Hospital, Greenville, North Carolina 27834, United States; Completed

St. Joseph Regional Health Center, Bryan, Texas 77802, United States; Recruiting

West Texas Regional Poison Center at Thomason Hospital, El Paso, Texas 79905, United States; Recruiting

Scott and White Memorial Hospital, Temple, Texas 76508, United States; Recruiting

Information about poisonous animals

Starting date: May 2008
Last updated: February 19, 2011