Snake EnvenomationPhase 4NCT00303303
The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations
A Phase 4 study testing Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy) in people with Snake Envenomation, run by Wake Forest University Health Sciences at 4 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 months and older
- Conditions the study is for
- Snake Envenomation
- What is being tested?
- Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 4 sitesUnited States
- Study dates
- Apr 2005to May 2008
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Envenomation by copperhead snake (Agkistrodon contortrix) within 6 hours
- Mild or moderate severity envenomation
Who cannot join
- Allergy to antivenom or components
- Severe envenomation (hypotension, severe swelling, compartment syndrome, bleeding, etc.)
- Uncertain snake ID
- Prior treatment with antivenom
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Carolinas Medical Center
Charlotte, North Carolina, 28232
Richland Memorial Hospital
Columbia, South Carolina, 29203
Duke University Medical Center
Durham, North Carolina, 27710
Medical College of Virigina/Virginia Commonwealth University Hospital
Richmond, Virginia, 23298
About this study
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:
- initial stabilizing dose of antivenom, followed by maintenance therapy,
- initial stabilizing dose of antivenom followed by placebo in lieu of maintenance therapy, or
- 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
- Snake Envenomation
- Being tested
- Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy), Crotaline Immune Fab (ovine) (active initial therapy; placebo maintenance therapy), Placebo
- Keywords
- Snake envenomation, Antivenins, Disability evaluation, Activities of daily living
- Medical subject headings
- Snake Bites
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy)Biological
Also called CroFab (tm)
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.
Crotaline Immune Fab (ovine) (active initial therapy; placebo maintenance therapy)Biological
Also called CroFab (tm)
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.
PlaceboBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Fab initial and maintenance therapy | Experimental | Active Fab Antivenom initial therapy followed by active Fab antivenom maintenance therapy Receives: Biological: Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy) |
| Fab initial therapy; placebo maintenance | Experimental | Active initial Fab antivenom therapy followed by placebo maintenance therapy. Receives: Biological: Crotaline Immune Fab (ovine) (active initial therapy; placebo maintenance therapy) |
| Placebo initial and maintenance therapy | Placebo comparator | Placebo initial and maintenance therapy. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Limb Function: AMA Disability Rating Score of Envenomated Limb
The range of possible scores is 0 - 100, and a lower score denotes less disability.
Measured: 14 days
Limb Function: AAOS Normative Outcome Study Scoring for Envenomated Limb
Score ranges from 0-100 with higher scores meaning better function.
Measured: 14 days
Limb Function: AAOS Normative Outcome Study Scoring for Envenomated Limb
Score ranges from 0-100 with higher scores meaning better function.
Measured: 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.
Measured: 14 days
Secondary outcomes (8)
Pain: Visual Analog Score
0-100 mm visual analog scale. Lower scores mean less pain.
Measured: 14 days
Pain Medication Use
Mg of morphine equivalents
Measured: 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
Measured: 12 months
Swelling: % Change in Volume Compared to Contralateral (Non-envenomated) Limb
Measured: 14 days
Limb Function: Return to Work
Measured: Week 4
Limb Function: Physical or Occupational Therapy Sessions Attended
Measured: Week 4
Hematological: Clotting Studies and Platelet Counts
Measured: 12 months
Complications of Therapy
Number of participants with acute hypersensitivity reactions
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2006 (estimated)
- Study startApr 2005
- Primary completionMay 2008
- Study completionMay 2008
Why it stopped: Study terminated due to declining enrollment; data analysis proceeding.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Snake EnvenomationStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- William P Kerns, MD, Principal investigator, Carolinas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00303303
- Sponsor's protocol ID
- 06-01-12B
- Status last verified
- Aug 2013
- First submitted
- 14 Mar 2006
- Last updated
- 1 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy of Crotaline Fab Antivenom for Copperhead Snake Envenomations
- ClinicalTrials.gov ID
- NCT00303303
- Acronym / sponsor ID
- 06-01-12B
- Conditions
- Snake Envenomation
- Keywords
- Snake envenomation, Antivenins, Disability evaluation, Activities of daily living
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated due to declining enrollment; data analysis proceeding.
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Study start
- Apr 2005
- Primary completion
- May 2008 (actual)
- Study completion
- May 2008 (actual)
- First posted
- 16 Mar 2006 (estimated)
- Results
- Posted 1 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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:
- initial stabilizing dose of antivenom, followed by maintenance therapy,
- initial stabilizing dose of antivenom followed by placebo in lieu of maintenance therapy, or
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Fab initial and maintenance therapy | Experimental | Biological: Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy)Active Fab Antivenom initial therapy followed by active Fab antivenom maintenance therapy |
| Fab initial therapy; placebo maintenance | Experimental | Biological: Crotaline Immune Fab (ovine) (active initial therapy; placebo maintenance therapy)Active initial Fab antivenom therapy followed by placebo maintenance therapy. |
| Placebo initial and maintenance therapy | Placebo comparator | Biological: PlaceboPlacebo initial and maintenance therapy. |
Who may qualify
- Ages
- 12 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Envenomation by copperhead snake (Agkistrodon contortrix) within 6 hours
- Mild or moderate severity envenomation
Key exclusion criteria (4 listed)
- Allergy to antivenom or components
- Severe envenomation (hypotension, severe swelling, compartment syndrome, bleeding, etc.)
- Uncertain snake ID
- Prior treatment with antivenom
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy)Also: CroFab (tm)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. | Biological | Fab initial and maintenance therapy |
| Crotaline Immune Fab (ovine) (active initial therapy; placebo maintenance therapy)Also: CroFab (tm)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. | Biological | Fab initial therapy; placebo maintenance |
| PlaceboPlacebo 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. | Biological | Placebo initial and maintenance therapy |
Primary outcome
Limb Function: AMA Disability Rating Score of Envenomated Limb
Time frame: 14 days
The range of possible scores is 0 - 100, and a lower score denotes less disability.
Limb Function: AAOS Normative Outcome Study Scoring for Envenomated Limb
Time frame: 14 days
Score ranges from 0-100 with higher scores meaning better function.
Limb Function: AAOS Normative Outcome Study Scoring for Envenomated Limb
Time frame: One year
Score ranges from 0-100 with higher scores meaning better function.
Limb Function: AAOS--time to Return to Normal Value
Time frame: 14 days
Score ranges from 0-100 with higher scores meaning better function. Time in days to return to baseline value.
8 secondary outcomes
Pain: Visual Analog Score
Time frame: 14 days
Pain Medication Use
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
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William P Kerns, MD principal investigator
Carolinas Medical Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Crotaline Polyvalent Immune Fab (ovine) (active initial and maintenance therapy) in people with Snake Envenomation, run by Wake Forest University Health Sciences at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Limb Function: AMA Disability Rating Score of Envenomated Limb (time frame: 14 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2023.