The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations

Wake Forest University (WFU)

Status and phase: Terminated; Phase 4

Conditions: Snake Envenomation

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

Study type: Interventional

Funder types: Other

Identifiers

NCT00303303

06-01-12B

Details and patient eligibility

About

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.

Full 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.

Enrollment: 13 patients

Sex: All

Ages: 12+ months old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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13 participants in 3 patient groups, including a placebo group

Fab initial and maintenance therapy

Experimental group

Description:

Active Fab Antivenom initial therapy followed by active Fab antivenom maintenance therapy

Treatment:

Biological: Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy)

Fab initial therapy; placebo maintenance

Experimental group

Description:

Active initial Fab antivenom therapy followed by placebo maintenance therapy.

Treatment:

Biological: Crotaline Immune Fab (ovine) (active initial therapy; placebo maintenance therapy)

Placebo initial and maintenance therapy

Placebo Comparator group

Description:

Placebo initial and maintenance therapy.

Treatment:

Biological: Placebo