The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations
Primary Purpose
Snake Envenomation
Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy)
Crotaline Immune Fab (ovine) (active initial therapy; placebo maintenance therapy)
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Snake Envenomation focused on measuring Snake envenomation, Antivenins, Disability evaluation, 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
Sites / Locations
- Carolinas Medical Center
- Duke University Medical Center
- Richland Memorial Hospital
- Medical College of Virigina/Virginia Commonwealth University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
1
2
3
Arm Description
Active initial and maintenance therapy
Active initial therapy; placebo maintenance therapy.
Placebo initial and maintenance therapy.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
Full Information
NCT ID
NCT00303303
First Posted
March 14, 2006
Last Updated
July 16, 2008
Sponsor
Wake Forest University Health Sciences
1. Study Identification
Unique Protocol Identification Number
NCT00303303
Brief Title
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
2. Study Status
Record Verification Date
July 2008
Overall Recruitment Status
Terminated
Why Stopped
Study terminated due to declining enrollment; data analysis proceeding.
Study Start Date
April 2005 (undefined)
Primary Completion Date
May 2008 (Actual)
Study Completion Date
May 2008 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Wake Forest University Health Sciences
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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):
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.
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Snake Envenomation
Keywords
Snake envenomation, Antivenins, Disability evaluation, Activities of daily living
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
25 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Active initial and maintenance therapy
Arm Title
2
Arm Type
Experimental
Arm Description
Active initial therapy; placebo maintenance therapy.
Arm Title
3
Arm Type
Placebo Comparator
Arm Description
Placebo initial and maintenance therapy.
Intervention Type
Biological
Intervention Name(s)
Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy)
Other Intervention Name(s)
CroFab (tm)
Intervention Description
Crotaline Polyvalent Immune Fab (Ovine), 4 vials initially; Second 4-vial dose two hours later if needed to achieve initial control of the envenomation syndrome; active maintenance therapy with 2 vials administered 6, 12, and 18 hours after initial control is achieved.
Intervention Type
Biological
Intervention Name(s)
Crotaline Immune Fab (ovine) (active initial therapy; placebo maintenance therapy)
Other Intervention Name(s)
CroFab (tm)
Intervention Description
Crotaline Polyvalent Immune Fab (Ovine), 4 vials initially; Second 4-vial dose two hours later if needed to achieve initial control of the envenomation syndrome; placebo maintenance therapy administered 6, 12, and 18 hours after initial control is achieved.
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Placebo therapy in place of initial and maintenance antivenom therapy. Note that open-label rescue therapy is mandated if the envenomation syndrome becomes severe, or if progression of envenomation signs/symptoms has not spontaneously halted by 6 hours.
Primary Outcome Measure Information:
Title
Limb function: AMA disability rating score of envenomated limb, time to recovery of 100% of premorbid function, Kaplan-Meier analysis
Time Frame
One year
Title
Limb function: AAOS Normative Outcome Study scoring for envenomated limb
Time Frame
14 days
Title
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
Secondary Outcome Measure Information:
Title
Pain: visual analog score
Time Frame
12 months
Title
Pain medication use: Mg of morphine equivalents
Time Frame
12 months
Title
Swelling: percentage (%) of limb spread proximal from bite site
Time Frame
12 months
Title
Swelling: % increase in volume compared to contralateral (non-envenomated) limb
Time Frame
12 months
Title
Limb function: return to work
Time Frame
12 months
Title
Limb function: physical or occupational therapy sessions attended
Time Frame
12 months
Title
Hematological: Clotting studies and platelet counts
Time Frame
12 months
Title
Complications of therapy
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Months
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William P Kerns, MD
Organizational Affiliation
Carolinas Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28232
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Richland Memorial Hospital
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29203
Country
United States
Facility Name
Medical College of Virigina/Virginia Commonwealth University Hospital
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
12. IPD Sharing Statement
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The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations
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