Clinical trial NCT00868309: A Comparison of Crotalinae Equine Immune F(ab)2 Antivenom (Anavip) and Crotalidae Polyvalent Immune Fab,
Official title: A Comparison of Anavip and CroFab in the Treatment of Subjects With Crotalinae (Pit Viper) Envenomation: A Randomized, Prospective, Open-Label, Controlled, Comparative, Multicenter Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Snake Bite
Blood Coagulation Disorders
Keywords: Snake Bite
Venom and antivenom kinetics
Lead sponsor: Instituto Bioclon S.A. de C.V.
Sponsor class: INDUSTRY
Collaborators: name: University of Arizona
First posted: 2009-03-24
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This phase II study was a prospective, randomized, open-label, multi-center study in the United States, involving patients from 18 to 70 years of age, comparing Anavip (Antivenin Crotalinae \[pit viper\] equine immune F(ab)2; Instituto Bioclon, Mexico City, Mexico) against CroFab (Protherics Inc., Nashville, Tennessee), the only currently approved product for treatment of Crotalinae (pit viper) envenomation in the US.

The study was designed to evaluate the hypothesis that lasting correction of snakebite induced thrombocytopenia and hypofibrinogenemia are possible following correction with F(ab)2 antivenom, by analyzing in detail the relationships among platelet count, fibrinogen, venom levels, and antivenom levels in subjects presenting with thrombocytopenia following crotaline viper envenomation. In the study we expected to see a fall in platelet count following Fab treatment, commensurate with that reported in the past. We hypothesized that following F(ab)2 treatment there would be a slower drop in post-treatment platelet counts, with a relatively higher platelet count at any given point in the follow-up period. We further hypothesized that an initial rise and later fall in platelet count would correspond with rise and fall in antivenom levels, and would be mirrored by concurrent drop and rise in levels of unbound circulating venom.

Detailed description: The overall objective of this Phase 2 open-label comparative study was to demonstrate that the F(ab)2 antivenom Anavip has significantly longer plasma persistence than does Fab, and that this is associated with a slower rise in venom levels and slower decline in platelet count and fibrinogen following hospital discharge of envenomated subjects. The effectiveness of F(ab)2 in preventing the recurrence of coagulopathies after the subject's discharge from hospital will indicate that, inherently, F(ab)2 antivenom has an improved safety profile relative to the Fab antivenom CroFab in treating envenomation by crotaline vipers.

Each subject was assessed for quantitative serum venom levels. Relatively few historical data exist to support the use of venom levels as a surrogate endpoint in envenomation. However, changes in venom levels have been correlated with coagulopathic effects, during both the acute phase of venom toxicity and the post treatment period of recurrent venom effect. Validation of this surrogate endpoint via correlation of venom effect with platelet count and fibrinogen level in this phase II study is intended to support future studies.

The secondary endpoints were the determination of coagulation abnormalities during the follow up period.

Eligibility criteria: Inclusion Criteria:

* men and women 18 to 70 years of age
* presenting for emergency treatment of pit viper bite
* informed consent document read and signed by subject

Exclusion Criteria:

* allergy to horse serum, sheep serum, or papaya
* current use of any antivenom, or use within the last month
* current participation in a clinical drug study, or participation within the last month
* pregnancy or breast-feeding
* underlying medical conditions that significantly alter blood coagulation: thrombocytopenia, hemophilia, familial dysfibrinogenemia, leukemia, recent ingestion of superwarfarin compounds (rat poison)
* use of any medication expected to affect platelet count, coagulation factors, or fibrinogen: chemotherapeutic agents, warfarin, heparin, aspirin
* No clinical indications of snake bite envenomation

Primary outcomes:
measure: Detection of Plasma Venom Levels During the Post Acute Treatment Period.
timeFrame: Follow up after Maintenance doses were completed. Two Weeks.
Secondary outcomes:
measure: >50,000 Platelets/mm3
timeFrame: Follow up after maintenance dose
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Tucson snakebite investigational site
state: Arizona
Study officials:
affiliation: Instituto Bioclon
name: Walter García, MD
role: STUDY_DIRECTOR
affiliation: University of Arizona
name: Leslie Boyer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto de Biotecnología UNAM
name: Alejandro Alagón, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: