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
  Purpose

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.


Condition Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations

Further study details as provided by Carolinas Healthcare System:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 25
Study Start Date: April 2005
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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)
Experimental: 2
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.
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.

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

Ages Eligible for Study:   12 Months and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00303303

Locations
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
Sponsors and Collaborators
Carolinas Healthcare System
Investigators
Principal Investigator: William P Kerns, MD Carolinas Medical Center
  More Information

No publications provided

Responsible Party: William P. Kerns III, MD, Carolinas HealthCare System
ClinicalTrials.gov Identifier: NCT00303303     History of Changes
Other Study ID Numbers: 06-01-12B
Study First Received: March 14, 2006
Last Updated: July 16, 2008
Health Authority: United States: Institutional Review Board

Keywords provided by Carolinas Healthcare System:
Snake envenomation
Antivenins
Disability evaluation
Activities of daily living

Additional relevant MeSH terms:
Snake Bites
Poisoning
Bites and Stings
Chemically-Induced Disorders
Wounds and Injuries
Antivenins
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014