The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations
|ClinicalTrials.gov Identifier: NCT00303303|
Recruitment Status : Terminated (Study terminated due to declining enrollment; data analysis proceeding.)
First Posted : March 16, 2006
Last Update Posted : July 18, 2008
|Condition or disease||Intervention/treatment||Phase|
|Snake Envenomation||Biological: Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy) Biological: Crotaline Immune Fab (ovine) (active initial therapy; placebo maintenance therapy) Biological: Placebo||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations|
|Study Start Date :||April 2005|
|Actual Primary Completion Date :||May 2008|
|Actual Study Completion Date :||May 2008|
Active initial and maintenance therapy
Biological: Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy)
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.
Other Name: CroFab (tm)
Active initial therapy; placebo maintenance therapy.
Biological: Crotaline Immune Fab (ovine) (active initial therapy; placebo maintenance therapy)
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.
Other Name: CroFab (tm)
Placebo Comparator: 3
Placebo initial and maintenance therapy.
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.
- Limb function: AMA disability rating score of envenomated limb, time to recovery of 100% of premorbid function, Kaplan-Meier analysis [ Time Frame: One year ]
- Limb function: AAOS Normative Outcome Study scoring for envenomated limb [ Time Frame: 14 days ]
- 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 ]
- Pain: visual analog score [ Time Frame: 12 months ]
- Pain medication use: Mg of morphine equivalents [ Time Frame: 12 months ]
- Swelling: percentage (%) of limb spread proximal from bite site [ Time Frame: 12 months ]
- Swelling: % increase in volume compared to contralateral (non-envenomated) limb [ Time Frame: 12 months ]
- Limb function: return to work [ Time Frame: 12 months ]
- Limb function: physical or occupational therapy sessions attended [ Time Frame: 12 months ]
- Hematological: Clotting studies and platelet counts [ Time Frame: 12 months ]
- Complications of therapy [ Time Frame: 12 months ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00303303
|United States, North Carolina|
|Carolinas Medical Center|
|Charlotte, North Carolina, United States, 28232|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|United States, South Carolina|
|Richland Memorial Hospital|
|Columbia, South Carolina, United States, 29203|
|United States, Virginia|
|Medical College of Virigina/Virginia Commonwealth University Hospital|
|Richmond, Virginia, United States, 23298|
|Principal Investigator:||William P Kerns, MD||Carolinas Medical Center|