Clinical trial NCT00303303: The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations
Official title: The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Snake Envenomation
Keywords: Snake envenomation
Antivenins
Disability evaluation
Activities of daily living
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2006-03-16
Enrollment: 13
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Limb Function: AMA Disability Rating Score of Envenomated Limb
timeFrame: 14 days
measure: Limb Function: AAOS Normative Outcome Study Scoring for Envenomated Limb
timeFrame: 14 days
measure: Limb Function: AAOS Normative Outcome Study Scoring for Envenomated Limb
timeFrame: One year
measure: Limb Function: AAOS--time to Return to Normal Value
timeFrame: 14 days
Secondary outcomes:
measure: Pain: Visual Analog Score
timeFrame: 14 days
measure: Pain Medication Use
timeFrame: First 6 hours from baseline, first 18 hours from baseline, First 24 hours from baseline, 12 months
measure: Swelling: Percentage (%) of Limb Spread Proximal From Bite Site
timeFrame: 12 months
measure: Swelling: % Change in Volume Compared to Contralateral (Non-envenomated) Limb
timeFrame: 14 days
measure: Limb Function: Return to Work
timeFrame: Week 4
measure: Limb Function: Physical or Occupational Therapy Sessions Attended
timeFrame: Week 4
measure: Hematological: Clotting Studies and Platelet Counts
timeFrame: 12 months
measure: Complications of Therapy
timeFrame: 12 months
Other outcomes:
Locations:
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbia
country: United States
facility: Richland Memorial Hospital
state: South Carolina
city: Richmond
country: United States
facility: Medical College of Virigina/Virginia Commonwealth University Hospital
state: Virginia
Study officials:
affiliation: Carolinas Medical Center
name: William P Kerns, MD
role: PRINCIPAL_INVESTIGATOR
References: