Clinical trial NCT00636116: Phase 3 Multicenter Comparative Study to Confirm Safety and Effectiveness of the F(ab)2 Antivenom Anavip.
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Snake Bite
Keywords: snake bite
antivenin treatment
Lead sponsor: Instituto Bioclon S.A. de C.V.
Sponsor class: INDUSTRY
Collaborators: name: Universidad Nacional Autonoma de Mexico
name: University of Arizona
First posted: 2008-03-14
Enrollment: 121
Sex: ALL
Minimum age (years): 2
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: 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.
timeFrame: Study Day 5 (±/- 1 day), Study Day 8 (±/- 1 day)
Secondary outcomes:
measure: 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
timeFrame: Study Day 5 (+/- 1 day) and Study Day 8 (+/- 1 day)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner Good Samaritan Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Maricopa Integrated Health System
state: Arizona
city: Phoenix
country: United States
facility: Northwest Medical Center
state: Arizona
city: Tucson
country: United States
facility: Tucson Medical Center
state: Arizona
city: Tucson
country: United States
facility: University Physicians Hospital
state: Arizona
city: Tucson
country: United States
facility: University Medical Center
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: Jacksonsville
country: United States
facility: Florida Poison Information Center
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Shreveport
country: United States
facility: LSU Health Sciences Center, Lousiana Poison Control Center
state: Louisiana
city: Kansas City
country: United States
facility: The Children's Mercy Hospital
state: Missouri
city: Albuquerque
country: United States
facility: The University of New Mexico Hospital
state: New Mexico
city: Greenville
country: United States
facility: Pitt County Memorial Hospital
state: North Carolina
city: Bryan
country: United States
facility: St. Joseph Regional Health Center
state: Texas
city: El Paso
country: United States
facility: West Texas Regional Poison Center at Thomason Hospital
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital
state: Texas
Study officials:
affiliation: Instituto Bioclon
name: Walter García Ubbelohde, MD
role: STUDY_DIRECTOR
References: