TerminatedNCT00303303Updated Dec 1, 2023Results posted

The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations

A Phase 4 interventional study of Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy) and Crotaline Immune Fab (ovine) (active initial therapy; placebo maintenance therapy) in Snake Envenomation, sponsored by Wake Forest University Health Sciences. Terminated at 4 sites in United States. Open to participants aged 12 Months and older. Per ClinicalTrials.gov, last updated 2023-12-01.

Sponsored by Wake Forest University Health Sciences · Phase 4, Interventional, and Treatment

Why this study was terminated

Study terminated due to declining enrollment; data analysis proceeding.

Phase: Phase 4
Study type: Interventional
Enrollment: 13
Allocation: Randomized
Ages: 12 Months and older
Sex: All

Study 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.

Read the 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.

Conditions studied

Snake Envenomation

Browse trials for

Snake Bites 38

Keywords

Snake envenomation
Antivenins
Disability evaluation
Activities of daily living

In context

Snake Bites

38 studies on the registry are indexed under Snake Bites; 11 are open to participants now.

This study's enrollment of 13 is below the median of 70 across 18 interventional studies indexed under Snake Bites.

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Lead sponsor

Wake Forest University Health Sciences is the lead sponsor of 1,351 studies on the registry; 201 are open to participants now.

Of its 332 completed or terminated interventional studies of FDA-regulated products, 251 (76%) have results posted.

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Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 12 Months and older
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Envenomation by copperhead snake (Agkistrodon contortrix) within 6 hours
Mild or moderate severity envenomation

Exclusion criteria

Exclusion Criteria:

Allergy to antivenom or components
Severe envenomation (hypotension, severe swelling, compartment syndrome, bleeding, etc.)
Uncertain snake ID
Prior treatment with antivenom

Study design

Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 13 participants (actual)

Study arms

Experimental
Fab initial and maintenance therapy
Active Fab Antivenom initial therapy followed by active Fab antivenom maintenance therapy
Biological: Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy)
Experimental
Fab initial therapy; placebo maintenance
Active initial Fab antivenom therapy followed by placebo maintenance therapy.
Biological: Crotaline Immune Fab (ovine) (active initial therapy; placebo maintenance therapy)
Placebo comparator
Placebo initial and maintenance therapy
Placebo initial and maintenance therapy.
Biological: Placebo

Interventions

BiologicalCrotaline 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.
Also known as: CroFab (tm)
BiologicalCrotaline 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.
Also known as: CroFab (tm)
BiologicalPlacebo
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.

What researchers measure

Primary outcomes

Limb Function: AMA Disability Rating Score of Envenomated Limb
The range of possible scores is 0 - 100, and a lower score denotes less disability.
Time frame: 14 days
Limb Function: AAOS Normative Outcome Study Scoring for Envenomated Limb
Score ranges from 0-100 with higher scores meaning better function.
Time frame: 14 days
Limb Function: AAOS Normative Outcome Study Scoring for Envenomated Limb
Score ranges from 0-100 with higher scores meaning better function.
Time frame: One year
Limb Function: AAOS--time to Return to Normal Value
Score ranges from 0-100 with higher scores meaning better function. Time in days to return to baseline value.
Time frame: 14 days

Secondary outcomes

Pain: Visual Analog Score
0-100 mm visual analog scale. Lower scores mean less pain.
Time frame: 14 days
Pain Medication Use
Mg of morphine equivalents
Time frame: First 6 hours from baseline, first 18 hours from baseline, First 24 hours from baseline, 12 months
Swelling: Percentage (%) of Limb Spread Proximal From Bite Site
Time frame: 12 months
Swelling: % Change in Volume Compared to Contralateral (Non-envenomated) Limb
Time frame: 14 days
Limb Function: Return to Work
Time frame: Week 4
Limb Function: Physical or Occupational Therapy Sessions Attended
Time frame: Week 4
Hematological: Clotting Studies and Platelet Counts
Time frame: 12 months
Complications of Therapy
Number of participants with acute hypersensitivity reactions
Time frame: 12 months

Results

Posted Dec 1, 2023

Participant flow

Participant flow — Overall Study
Milestone	Fab Antivenom Followed by Fab Antivenom Maintenance	Fab Antivenom Followed by Placebo Maintenance Therapy	Placebo Initial Followed by Placebo Maintenance Therapy
Started	5	4	4
Completed	5	4	3
Not completed	0	0	1
Withdrew: Withdrawal by subject	0	0	1

Outcome measures

PrimaryLimb Function: AMA Disability Rating Score of Envenomated Limb

The range of possible scores is 0 - 100, and a lower score denotes less disability.

Time frame:: 14 days
Reported as:: Mean · units on a scale

Limb Function: AMA Disability Rating Score of Envenomated Limb
units on a scale	Group 1	Group 2	Group 3
Limb Function: AMA Disability Rating Score of Envenomated Limb	11.2 ± 17.20	7.75 ± 7.18	22.67 ± 24.70

PrimaryLimb Function: AAOS Normative Outcome Study Scoring for Envenomated Limb

Score ranges from 0-100 with higher scores meaning better function.

Time frame:: 14 days
Reported as:: Mean · score on a scale

Limb Function: AAOS Normative Outcome Study Scoring for Envenomated Limb
score on a scale	Fab Initial and Maintenance Therapy	Fab Initial Therapy; Placebo Maintenance	Placebo Initial and Maintenance Therapy
Limb Function: AAOS Normative Outcome Study Scoring for Envenomated Limb	48.4 ± 19.2	40.7 ± 14.7	40.3 ± 9.8

PrimaryLimb Function: AAOS Normative Outcome Study Scoring for Envenomated Limb

Score ranges from 0-100 with higher scores meaning better function.

Time frame:: One year
Reported as:: Mean · score on a scale

Limb Function: AAOS Normative Outcome Study Scoring for Envenomated Limb
score on a scale	Fab Antivenom Followed by Fab Antivenom Maintenance	Fab Antivenom Followed by Placebo Maintenance Therapy	Placebo Initial Followed by Placebo Maintenance Therapy
Limb Function: AAOS Normative Outcome Study Scoring for Envenomated Limb	55.78 ± 2.45	55.18 ± 2.04	54.09 ± 3.96

PrimaryLimb Function: AAOS--time to Return to Normal Value

Score ranges from 0-100 with higher scores meaning better function. Time in days to return to baseline value.

Time frame:: 14 days
Reported as:: Mean · days

Limb Function: AAOS--time to Return to Normal Value
days	Fab Antivenom Followed by Fab Antivenom Maintenance	Fab Antivenom Followed by Placebo Maintenance Therapy	Placebo Initial Followed by Placebo Maintenance Therapy
Limb Function: AAOS--time to Return to Normal Value	3.6 ± 2.8	5.5 ± 1.66	6.3 ± 1.70

SecondaryPain: Visual Analog Score

0-100 mm visual analog scale. Lower scores mean less pain.

Time frame:: 14 days
Reported as:: Mean · score on a scale

Pain: Visual Analog Score
score on a scale	Fab Antivenom Followed by Fab Antivenom Maintenance	Fab Antivenom Followed by Placebo Maintenance Therapy	Placebo Initial Followed by Placebo Maintenance Therapy
Pain: Visual Analog Score	.5 ± 1.0	6.5 ± 7.3	19.0 ± 18.7

SecondaryPain Medication Use

Mg of morphine equivalents

Time frame:: First 6 hours from baseline, first 18 hours from baseline, First 24 hours from baseline, 12 months
Reported as:: Mean · miligrams

Pain Medication Use
miligrams	Fab Antivenom Followed by Fab Antivenom Maintenance	Fab Antivenom Followed by Placebo Maintenance Therapy	Placebo Initial Followed by Placebo Maintenance Therapy
First 24 hours from baseline	5.2 ± 6.6	43.5 ± 40.5	29.9 ± 15.6
First 6 hours from baseline	4.4 ± 4.45	15.95 ± 9.32	13.1 ± 2.45
first 18 hours from baseline	.8 ± 1.6	27.5 ± 28.9	16.8 ± 13.38

SecondarySwelling: Percentage (%) of Limb Spread Proximal From Bite Site

Time frame:: 12 months

No measurements were reported for this outcome.

SecondarySwelling: % Change in Volume Compared to Contralateral (Non-envenomated) Limb

Time frame:: 14 days
Reported as:: Mean · percentage of change

Swelling: % Change in Volume Compared to Contralateral (Non-envenomated) Limb
percentage of change	Fab Antivenom Followed by Fab Antivenom Maintenance	Fab Antivenom Followed by Placebo Maintenance Therapy	Placebo Initial Followed by Placebo Maintenance Therapy
Swelling: % Change in Volume Compared to Contralateral (Non-envenomated) Limb	1 ± 5	2 ± 6	-8 ± 9

SecondaryLimb Function: Return to Work

Time frame:: Week 4
Reported as:: Median · days

Limb Function: Return to Work
days	Fab Antivenom Followed by Fab Antivenom Maintenance	Fab Antivenom Followed by Placebo Maintenance Therapy	Placebo Initial Followed by Placebo Maintenance Therapy
Limb Function: Return to Work	3.75 ± .25	4	—

SecondaryLimb Function: Physical or Occupational Therapy Sessions Attended

Time frame:: Week 4
Reported as:: Number · number of sessions

Limb Function: Physical or Occupational Therapy Sessions Attended
number of sessions	Fab Antivenom Followed by Fab Antivenom Maintenance	Fab Antivenom Followed by Placebo Maintenance Therapy	Placebo Initial Followed by Placebo Maintenance Therapy
Limb Function: Physical or Occupational Therapy Sessions Attended	0	0	0

SecondaryHematological: Clotting Studies and Platelet Counts

Time frame:: 12 months

No measurements were reported for this outcome.

SecondaryComplications of Therapy

Number of participants with acute hypersensitivity reactions

Time frame:: 12 months
Reported as:: Count of participants · Participants

Complications of Therapy
Participants	Fab Antivenom Followed by Fab Antivenom Maintenance	Fab Antivenom Followed by Placebo Maintenance Therapy	Placebo Initial Followed by Placebo Maintenance Therapy
Complications of Therapy	1	0	0

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Group 1	0/5 (0%)	0/5 (0%)	1/5 (20%)
Group 2	0/4 (0%)	0/4 (0%)	0/4 (0%)
Group 3	0/4 (0%)	0/4 (0%)	0/4 (0%)

Most frequent other events

Most frequent other events
Event	Group 1	Group 2	Group 3
Acute hypersensitivity reactionGeneral disorders	1/5	0/4	0/4
NauseaGastrointestinal disorders	1/5	0/4	0/4
HypotensionCardiac disorders	1/5	0/4	0/4
TachycardiaCardiac disorders	1/5	0/4	0/4

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Experimental: Fab Initial and Maintenance Therapy	Experimental: Fab Initial Therapy; Placebo Maintenance	Placebo Comparator: Placebo Initial and Maintenance Therapy	Total
<=18 years	1	0	0	1
Between 18 and 65 years	4	4	4	12
>=65 years	0	0	0	0

Age, Continuous
Age, Continuous(years)	Experimental: Fab Initial and Maintenance Therapy	Experimental: Fab Initial Therapy; Placebo Maintenance	Placebo Comparator: Placebo Initial and Maintenance Therapy	Total
Mean	35.4 ± 19.9	41 ± 14.9	39 ± 19	38.2 ± 16.6

Sex: Female, Male
Sex: Female, Male(Participants)	Experimental: Fab Initial and Maintenance Therapy	Experimental: Fab Initial Therapy; Placebo Maintenance	Placebo Comparator: Placebo Initial and Maintenance Therapy	Total
Female	4	1	3	8
Male	1	3	1	5

Region of Enrollment
Region of Enrollment(participants)	Experimental: Fab Initial and Maintenance Therapy	Experimental: Fab Initial Therapy; Placebo Maintenance	Placebo Comparator: Placebo Initial and Maintenance Therapy	Total
United States	5	4	4	13

Study locations

4 sites

Carolinas Medical Center
Charlotte, North Carolina 28232, United States
Duke University Medical Center
Durham, North Carolina 27710, United States
Richland Memorial Hospital
Columbia, South Carolina 29203, United States
Medical College of Virigina/Virginia Commonwealth University Hospital
Richmond, Virginia 23298, United States

Timeline

Tracking since Sep 25, 2026

Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Apr 2005, a primary completion of May 2008 and a completion of May 2008. It does not say whether these dates are actual or estimated.

Results were first posted in Dec 2023, 15 years 7 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered: Mar 14, 2006
First posted: Mar 16, 2006
Start: Apr 2005
Primary completionActual: May 2008
CompletionActual: May 2008
Results first posted: Dec 1, 2023
Last update: Dec 1, 2023

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Dec 1, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00303303
Lead sponsor: Wake Forest University Health Sciences
Responsible party: Sponsor
First posted: Mar 16, 2006
Start date: Apr 2005
Primary completion: May 2008
Completion: May 2008
Results posted: Dec 1, 2023
Last update: Dec 1, 2023

Study contacts

William P Kerns, MD

principal investigator · Carolinas Medical Center

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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