The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations

NCT ID: NCT00303303

Last Updated: 2023-12-01

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-04-30

Study Completion Date

2008-05-31

Brief Summary

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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

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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.

Conditions

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Snake Envenomation

Keywords

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Snake envenomation Antivenins Disability evaluation Activities of daily living

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Fab initial and maintenance therapy

Active Fab Antivenom initial therapy followed by active Fab antivenom maintenance therapy

Group Type EXPERIMENTAL

Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy)

Intervention Type BIOLOGICAL

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.

Fab initial therapy; placebo maintenance

Active initial Fab antivenom therapy followed by placebo maintenance therapy.

Group Type EXPERIMENTAL

Crotaline Immune Fab (ovine) (active initial therapy; placebo maintenance therapy)

Intervention Type BIOLOGICAL

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.

Placebo initial and maintenance therapy

Placebo initial and maintenance therapy.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

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.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type BIOLOGICAL

Other Intervention Names

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CroFab (tm) CroFab (tm)

Eligibility Criteria

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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
Minimum Eligible Age

12 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Wake Forest University Health Sciences

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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William P Kerns, MD

Role: PRINCIPAL_INVESTIGATOR

Carolinas Medical Center

Locations

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Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Richland Memorial Hospital

Columbia, South Carolina, United States

Site Status

Medical College of Virigina/Virginia Commonwealth University Hospital

Richmond, Virginia, United States

Site Status

Countries

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United States

Other Identifiers

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06-01-12B

Identifier Type: -

Identifier Source: org_study_id