Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations

This study has been terminated.
(Study terminated due to declining enrollment; data analysis proceeding.)
Sponsor:
Information provided by:
Carolinas Healthcare System
ClinicalTrials.gov Identifier:
NCT00303303
First received: March 14, 2006
Last updated: July 16, 2008
Last verified: July 2008

March 14, 2006
July 16, 2008
April 2005
May 2008   (final data collection date for primary outcome measure)
  • 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 ]
  • 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, 14 days
  • Limb function: AAOS Normative Outcome Study scoring for envenomated limb,time to recovery of 100% of premorbid function, Kaplan-Meier analysis
  • Limb function: AMA disability rating score of envenomated limb, at 14 days
Complete list of historical versions of study NCT00303303 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Pain: Visual analog score, multiple time points, 1 hr - 12 months
  • Pain medication use: Mg of morphine equivalents, multiple time points, 1 hr - 12 months
  • Swelling: % of limb spread proximal from bite site, multiple time points, 1 hr - 12 months
  • Swelling: % increase in volume compared to contralateral (normal) limg, multiple time points, 1 hr - 12 months
  • Limb function: Return to work
  • Limb function: Physical or occupational therapy sessions attended
  • Hematological: Clotting studies and platelet counts, multiple time points, 1 hr - 2 weeks
  • Complications of therapy
Not Provided
Not Provided
 
The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations
The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Snake Envenomation
  • 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)
  • 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)
  • Biological: Placebo
    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.
  • Experimental: 1
    Active initial and maintenance therapy
    Intervention: Biological: Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy)
  • Experimental: 2
    Active initial therapy; placebo maintenance therapy.
    Intervention: Biological: Crotaline Immune Fab (ovine) (active initial therapy; placebo maintenance therapy)
  • Placebo Comparator: 3
    Placebo initial and maintenance therapy.
    Intervention: Biological: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
25
May 2008
May 2008   (final data collection date for primary outcome measure)

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
Both
12 Months and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00303303
06-01-12B
Yes
William P. Kerns III, MD, Carolinas HealthCare System
Carolinas Healthcare System
Not Provided
Principal Investigator: William P Kerns, MD Carolinas Medical Center
Carolinas Healthcare System
July 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP