The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations

November 6, 2023 updated by: Wake Forest University Health Sciences
Most patients bitten by copperhead snakes do not currently receive antivenom. Some snakebite victims have long term problems with the function of the limb that was bitten. This study will determine whether early administration of antivenom to patients with mild to moderate copperhead snakebites reduces long-term complications.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This study seeks to answer three important questions about the role of ovine (sheep-derived) antivenom in the treatment of people bitten by copperhead snakes (Agkistrodon contortrix):

  1. Although ovine antivenom has been approved by the FDA for treatment of copperhead envenomation, copperhead victims were excluded from the previous clinical trials. Animal experiments and retrospective human data suggest that the antivenom probably does work for copperhead snakebite, at least in the short term. This study will determine whether the antivenom is actually effective in reducing pain, swelling, and other immediate effects of copperhead snakebite.
  2. Deaths from copperhead snakebite are extremely rare, but survivors often report long term problems with pain and swelling in the envenomated limb. No study has formally measured the long-term outcomes in untreated snakebite, nor whether antivenom has any benefit in reducing the duration or severity of these complications. This study will answer this question through formal assessments of limb function up to 12 months after treatment.
  3. After initial control of the signs and symptoms of snakebite is achieved with antivenom therapy, some patients develop recurrent swelling or blood clotting problems. A randomized controlled trial in rattlesnake victims showed that the frequency of these problems is reduced by administration of 6 additional vials of antivenom over 18 hours ("maintenance therapy"). However, blood clotting problems are uncommon in copperhead snakebite even without antivenom treatment, and a retrospective trial suggested that maintenance therapy may have no effect on the frequency of delayed swelling in copperhead victims. In the typical copperhead victim, maintenance therapy increases the cost of treatment by more than 100%. This study will determine whether maintenance therapy is necessary in mild to moderate copperhead snakebite.

Patients are eligible for enrollment if they have been bitten by a snake positively identified as a copperhead within 6 hours of enrollment, if they have signs of mild or moderate severity envenomation, and if contraindications are not present.

After appropriate informed consent, patients are randomized to receive:

A. initial stabilizing dose of antivenom, followed by maintenance therapy,

B. initial stabilizing dose of antivenom followed by placebo in lieu of maintenance therapy, or

C. placebo for both initial dose and maintenance.

All laboratory testing, pain medication, hospitalization, and other therapies are standard for snakebite of this severity. If at any time the envenomation becomes severe, antivenom is administered.

In addition to the standard assessments performed on all snakebite victims (swelling, pain, vital signs, blood clotting, complications of therapy), patients in this study receive formal assessments of the function of the envenomated limb. This assessment uses the AMA disability rating system and the American Academy of Orthopedic Surgeons' Normative Outcomes Study questionnaire do determine how well the limbs function and how well the limbs perform and how much any remaining problems interfere with the patients' long-term happiness and ability to perform common activities of daily living.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 4

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
    • North Carolina
      • Charlotte, North Carolina, United States, 28232
        • Carolinas Medical Center
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • South Carolina
      • Columbia, South Carolina, United States, 29203
        • Richland Memorial Hospital
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Medical College of Virigina/Virginia Commonwealth University 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

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Envenomation by copperhead snake (Agkistrodon contortrix) within 6 hours
  • Mild or moderate severity envenomation

Exclusion Criteria:

  • Allergy to antivenom or components
  • Severe envenomation (hypotension, severe swelling, compartment syndrome, bleeding, etc.)
  • Uncertain snake ID
  • Prior treatment with antivenom

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: Fab initial and maintenance therapy
Active Fab Antivenom initial therapy followed by active Fab antivenom maintenance therapy
Biological: Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy)
Crotaline Polyvalent Immune Fab (Ovine), 4 vials initially; Second 4-vial dose two hours later if needed to achieve initial control of the envenomation syndrome; active maintenance therapy with 2 vials administered 6, 12, and 18 hours after initial control is achieved.
Other Names:
  • CroFab (tm)
Experimental: Fab initial therapy; placebo maintenance
Active initial Fab antivenom therapy followed by placebo maintenance therapy.
Biological: Crotaline Immune Fab (ovine) (active initial therapy; placebo maintenance therapy)
Crotaline Polyvalent Immune Fab (Ovine), 4 vials initially; Second 4-vial dose two hours later if needed to achieve initial control of the envenomation syndrome; placebo maintenance therapy administered 6, 12, and 18 hours after initial control is achieved.
Other Names:
  • CroFab (tm)
Placebo Comparator: Placebo initial and maintenance therapy
Placebo initial and maintenance therapy.
Biological: Placebo
Placebo therapy in place of initial and maintenance antivenom therapy. Note that open-label rescue therapy is mandated if the envenomation syndrome becomes severe, or if progression of envenomation signs/symptoms has not spontaneously halted by 6 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Limb Function: AMA Disability Rating Score of Envenomated Limb
Time Frame: 14 days
The range of possible scores is 0 - 100, and a lower score denotes less disability.
14 days
Limb Function: AAOS Normative Outcome Study Scoring for Envenomated Limb
Time Frame: 14 days
Score ranges from 0-100 with higher scores meaning better function.
14 days
Limb Function: AAOS Normative Outcome Study Scoring for Envenomated Limb
Time Frame: One year
Score ranges from 0-100 with higher scores meaning better function.
One year
Limb Function: AAOS--time to Return to Normal Value
Time Frame: 14 days
Score ranges from 0-100 with higher scores meaning better function. Time in days to return to baseline value.
14 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain: Visual Analog Score
Time Frame: 14 days
0-100 mm visual analog scale. Lower scores mean less pain.
14 days
Pain Medication Use
Time Frame: First 6 hours from baseline, first 18 hours from baseline, First 24 hours from baseline, 12 months
Mg of morphine equivalents
First 6 hours from baseline, first 18 hours from baseline, First 24 hours from baseline, 12 months
Swelling: Percentage (%) of Limb Spread Proximal From Bite Site
Time Frame: 12 months
12 months
Swelling: % Change in Volume Compared to Contralateral (Non-envenomated) Limb
Time Frame: 14 days
14 days
Limb Function: Return to Work
Time Frame: Week 4
Week 4
Limb Function: Physical or Occupational Therapy Sessions Attended
Time Frame: Week 4
Week 4
Hematological: Clotting Studies and Platelet Counts
Time Frame: 12 months
12 months
Complications of Therapy
Time Frame: 12 months
Number of participants with acute hypersensitivity reactions
12 months

Collaborators and Investigators

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

Sponsor

Wake Forest University Health Sciences

Investigators

  • Principal Investigator: William P Kerns, MD, Carolinas Medical Center

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

April 1, 2005

Primary Completion (Actual)

May 1, 2008

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

March 14, 2006

First Submitted That Met QC Criteria

March 14, 2006

First Posted (Estimated)

March 16, 2006

Study Record Updates

Last Update Posted (Estimated)

December 1, 2023

Last Update Submitted That Met QC Criteria

November 6, 2023

Last Verified

August 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06-01-12B

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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