The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations

• Limb function: AMA disability rating score of envenomated limb, time to recovery of 100% of premorbid function, Kaplan-Meier analysis [ Time Frame: One year ] [ Designated as safety issue: No ]
  
• Limb function: AAOS Normative Outcome Study scoring for envenomated limb [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  
• Limb function: AAOS Normative Outcome Study scoring for envenomated limb, time to recovery of 100% of premorbid function, Kaplan-Meier analysis [ Time Frame: One year ] [ Designated as safety issue: No ]
  

• Pain: visual analog score [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  
• Pain medication use: Mg of morphine equivalents [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  
• Swelling: percentage (%) of limb spread proximal from bite site [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  
• Swelling: % increase in volume compared to contralateral (non-envenomated) limb [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  
• Limb function: return to work [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  
• Limb function: physical or occupational therapy sessions attended [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  
• Hematological: Clotting studies and platelet counts [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  
• Complications of therapy [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  

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.