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

Sponsor:	Instituto Bioclon S.A. de C.V.
Collaborators:	Instituto de Biotecnologia,UNAM, Cuernavaca Mexico University of Arizona
Information provided by (Responsible Party):	Instituto Bioclon S.A. de C.V.
ClinicalTrials.gov Identifier:	NCT00636116

Purpose

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.

Condition	Intervention	Phase
Snake Bite	Biological: Crotalinae (pit viper) equine immune F(ab)2 Biological: Crotalidae Polyvalent Immune Fab, ovine	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Comparison of Anavip® and CroFab® in the Treatment of Patients With Crotalinae Envenomation: A Randomized, Prospective, Blinded, Controlled, Comparative, Multicenter Study

Resource links provided by NLM:

MedlinePlus related topics: Bleeding Disorders

U.S. FDA Resources

Further study details as provided by Instituto Bioclon S.A. de C.V.:

Primary Outcome Measures:

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. [ Time Frame: Study Day 5 (±/- 1 day), Study Day 8 (±/- 1 day) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 [ Time Frame: Study Day 5 (+/- 1 day) and Study Day 8 (+/- 1 day) ] [ Designated as safety issue: Yes ]

Enrollment:	121
Study Start Date:	May 2008
Study Completion Date:	January 2012
Primary Completion Date:	November 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group 1 Anavip with Anavip Maintenance Therapy	Biological: Crotalinae (pit viper) equine immune F(ab)2 Anavip with Anavip Maintenance Therapy Other Name: Anavip
Experimental: Group 2 Anavip with Placebo Maintenance Therapy	Biological: Crotalinae (pit viper) equine immune F(ab)2 Anavip with Placebo Maintenance Therapy Other Name: Anavip
Active Comparator: Group 3 CroFab with CroFab Maintenance Therapy	Biological: Crotalidae Polyvalent Immune Fab, ovine CroFab with CroFab Maintenance Therapy Other Name: CroFab

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

Ages Eligible for Study:	2 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00636116

Locations

United States, Arizona
Northwest Medical Center
Phoenix, Arizona, United States, 85741
Banner Good Samaritan Medical Center
Phoenix, Arizona, United States, 85006
Maricopa Integrated Health System
Phoenix, Arizona, United States, 85008
University Physicians Hospital
Tucson, Arizona, United States, 85713
Tucson Medical Center
Tucson, Arizona, United States, 85712
University Medical Center
Tucson, Arizona, United States, 85721
United States, California
Loma Linda University Medical Center
Loma Linda, California, United States, 92354
Rady Children's Hospital
San Diego, California, United States, 92123
University of California San Diego
San Diego, California, United States, 92103
United States, Florida
Florida Poison Information Center
Jacksonsville, Florida, United States, 32209
Sarasota Memorial Hospital
Sarasota, Florida, United States, 34239
United States, Louisiana
LSU Health Sciences Center, Lousiana Poison Control Center
Shreveport, Louisiana, United States, 71103
United States, Missouri
The Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
United States, New Mexico
The University of New Mexico Hospital
Albuquerque, New Mexico, United States, 87106
United States, North Carolina
Pitt County Memorial Hospital
Greenville, North Carolina, United States, 27834
United States, Texas
St. Joseph Regional Health Center
Bryan, Texas, United States, 77802
West Texas Regional Poison Center at Thomason Hospital
El Paso, Texas, United States, 79905
Scott and White Memorial Hospital
Temple, Texas, United States, 76508

Sponsors and Collaborators

Instituto Bioclon S.A. de C.V.

Instituto de Biotecnologia,UNAM, Cuernavaca Mexico

University of Arizona

Investigators

Study Director:

Walter García Ubbelohde, MD

Instituto Bioclon

More Information

Additional Information:

Information about poisonous animals This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Instituto Bioclon S.A. de C.V.
ClinicalTrials.gov Identifier:	NCT00636116 History of Changes
Obsolete Identifiers:	NCT00884156
Other Study ID Numbers:	YA-07/02
Study First Received:	March 11, 2008
Last Updated:	January 9, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Instituto Bioclon S.A. de C.V.:

snake bite
antivenin treatment

Additional relevant MeSH terms:

Snake Bites
Bites and Stings
Poisoning
Substance-Related Disorders

ClinicalTrials.gov processed this record on February 09, 2012