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

January 9, 2012 updated by: Instituto Bioclon S.A. de C.V.

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

121

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 80 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1
Anavip with Anavip Maintenance Therapy
Biological: Crotalinae (pit viper) equine immune F(ab)2
Anavip with Anavip Maintenance Therapy
Other Names:
  • Anavip
Biological: Crotalinae (pit viper) equine immune F(ab)2
Anavip with Placebo Maintenance Therapy
Other Names:
  • Anavip
Experimental: Group 2
Anavip with Placebo Maintenance Therapy
Biological: Crotalinae (pit viper) equine immune F(ab)2
Anavip with Anavip Maintenance Therapy
Other Names:
  • Anavip
Biological: Crotalinae (pit viper) equine immune F(ab)2
Anavip with Placebo Maintenance Therapy
Other Names:
  • Anavip
Active Comparator: Group 3
CroFab with CroFab Maintenance Therapy
Biological: Crotalidae Polyvalent Immune Fab, ovine
CroFab with CroFab Maintenance Therapy
Other Names:
  • CroFab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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)
Study Day 5 (±/- 1 day), Study Day 8 (±/- 1 day)

Secondary Outcome Measures

Outcome Measure
Time Frame
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)
Study Day 5 (+/- 1 day) and Study Day 8 (+/- 1 day)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Bioclon S.A. de C.V.

Collaborators

University of Arizona
Universidad Nacional Autonoma de Mexico

Investigators

  • Study Director: Walter Garcia Ubbelohde, MD, Instituto Bioclon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2008

Primary Completion (Actual)

November 1, 2011

Study Completion (Actual)

January 1, 2012

Study Registration Dates

First Submitted

March 11, 2008

First Submitted That Met QC Criteria

March 11, 2008

First Posted (Estimate)

March 14, 2008

Study Record Updates

Last Update Posted (Estimate)

January 10, 2012

Last Update Submitted That Met QC Criteria

January 9, 2012

Last Verified

January 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • YA-07/02

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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