The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations
- Conditions
- Snake Envenomation
- Interventions
- Biological: Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy)Biological: Crotaline Immune Fab (ovine) (active initial therapy; placebo maintenance therapy)Biological: Placebo
- Registration Number
- NCT00303303
- Lead Sponsor
- Wake Forest University Health Sciences
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 13
- Envenomation by copperhead snake (Agkistrodon contortrix) within 6 hours
- Mild or moderate severity envenomation
- Allergy to antivenom or components
- Severe envenomation (hypotension, severe swelling, compartment syndrome, bleeding, etc.)
- Uncertain snake ID
- Prior treatment with antivenom
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Fab initial and maintenance therapy Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy) Active Fab Antivenom initial therapy followed by active Fab antivenom maintenance therapy Fab initial therapy; placebo maintenance Crotaline Immune Fab (ovine) (active initial therapy; placebo maintenance therapy) Active initial Fab antivenom therapy followed by placebo maintenance therapy. Placebo initial and maintenance therapy Placebo Placebo initial and maintenance therapy.
- Primary Outcome Measures
Name Time Method Limb Function: AMA Disability Rating Score of Envenomated Limb 14 days The range of possible scores is 0 - 100, and a lower score denotes less disability.
Limb Function: AAOS Normative Outcome Study Scoring for Envenomated Limb One year Score ranges from 0-100 with higher scores meaning better function.
Limb Function: AAOS--time to Return to Normal Value 14 days Score ranges from 0-100 with higher scores meaning better function. Time in days to return to baseline value.
- Secondary Outcome Measures
Name Time Method Pain Medication Use First 6 hours from baseline, first 18 hours from baseline, First 24 hours from baseline, 12 months Mg of morphine equivalents
Swelling: % Change in Volume Compared to Contralateral (Non-envenomated) Limb 14 days Limb Function: Physical or Occupational Therapy Sessions Attended Week 4 Pain: Visual Analog Score 14 days 0-100 mm visual analog scale. Lower scores mean less pain.
Swelling: Percentage (%) of Limb Spread Proximal From Bite Site 12 months Hematological: Clotting Studies and Platelet Counts 12 months Limb Function: Return to Work Week 4 Complications of Therapy 12 months Number of participants with acute hypersensitivity reactions
Trial Locations
- Locations (4)
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Richland Memorial Hospital
🇺🇸Columbia, South Carolina, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Medical College of Virigina/Virginia Commonwealth University Hospital
🇺🇸Richmond, Virginia, United States