The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations

Condition(s) targeted: Snake Envenomation

Intervention: Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy) (Biological); Crotaline Immune Fab (ovine) (active initial therapy; placebo maintenance therapy) (Biological); Placebo (Biological)

Phase: Phase 4

Status: Recruiting

Sponsored by: Carolinas Healthcare System

Official(s) and/or principal investigator(s):
William P Kerns, MD, Principal Investigator, Affiliation: Carolinas Medical Center

Overall contact:
William P Kerns, MD, Phone: 704-355-4212, Email: rkerns@carolinas.org

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.

Official title: The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

Limb function: AMA disability rating score of envenomated limb, time to recovery of 100% of premorbid function, Kaplan-Meier analysis

Limb function: AAOS Normative Outcome Study scoring for envenomated limb

Limb function: AAOS Normative Outcome Study scoring for envenomated limb, time to recovery of 100% of premorbid function, Kaplan-Meier analysis

Limb function: AAOS Normative Outcome Study scoring for envenomated limb

Secondary outcome:

Pain: visual analog score

Pain medication use: Mg of morphine equivalents

Swelling: percentage (%) of limb spread proximal from bite site

Swelling: % increase in volume compared to contralateral (non-envenomated) limb

Limb function: return to work

Limb function: physical or occupational therapy sessions attended

Hematological: Clotting studies and platelet counts

Complications of therapy

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.

Minimum age: 12 Months. Maximum age: N/A. Gender(s): Both.

Criteria:

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

William P Kerns, MD, Phone: 704-355-4212, Email: rkerns@carolinas.org

Carolinas Medical Center, Charlotte, North Carolina 28232, United States; Recruiting
William P Kerns, MD

Duke University Medical Center, Durham, North Carolina 27710, United States; Recruiting
Charles Gerardo, MD

Richland Memorial Hospital, Columbia, South Carolina 29203, United States; Recruiting
William Richardson, MD

Medical College of Virigina/Virginia Commonwealth University Hospital, Richmond, Virginia 23298, United States; Recruiting
Kenneth Whitlow, MD

Starting date: April 2005
Ending date: December 2009
Last updated: May 2, 2008