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

Snake Bite Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00636116
• Other study ID #: YA-07/02
• Status: Completed
• Phase: Phase 3
• First received: March 11, 2008
• Last updated: January 9, 2012
• Start date: May 2008
• Est. completion date: January 2012

Study information

• Verified date: January 2012
• Source: Instituto Bioclon S.A. de C.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00884156

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: January 2012
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Snake Bite
• Snake Bites

Intervention

Biological:
• Crotalinae (pit viper) equine immune F(ab)2
Anavip with Anavip Maintenance Therapy
• Crotalinae (pit viper) equine immune F(ab)2
Anavip with Placebo Maintenance Therapy
• Crotalidae Polyvalent Immune Fab, ovine
CroFab with CroFab Maintenance Therapy

Locations

Country	Name	City	State
United States	The University of New Mexico Hospital	Albuquerque	New Mexico
United States	St. Joseph Regional Health Center	Bryan	Texas
United States	West Texas Regional Poison Center at Thomason Hospital	El Paso	Texas
United States	Pitt County Memorial Hospital	Greenville	North Carolina
United States	Florida Poison Information Center	Jacksonsville	Florida
United States	The Children's Mercy Hospital	Kansas City	Missouri
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Banner Good Samaritan Medical Center	Phoenix	Arizona
United States	Maricopa Integrated Health System	Phoenix	Arizona
United States	Northwest Medical Center	Phoenix	Arizona
United States	Rady Children's Hospital	San Diego	California
United States	University of California San Diego	San Diego	California
United States	Sarasota Memorial Hospital	Sarasota	Florida
United States	LSU Health Sciences Center, Lousiana Poison Control Center	Shreveport	Louisiana
United States	Scott and White Memorial Hospital	Temple	Texas
United States	Tucson Medical Center	Tucson	Arizona
United States	University Medical Center	Tucson	Arizona
United States	University Physicians Hospital	Tucson	Arizona

Sponsors (3)

Lead Sponsor	Collaborator
Instituto Bioclon S.A. de C.V.	Universidad Nacional Autonoma de Mexico, University of Arizona

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)

External Links

•   Information about poisonous animals