Snake BitePhase 3NCT00636116
Phase 3 Multicenter Comparative Study to Confirm Safety and Effectiveness of the F(ab)2 Antivenom Anavip.
A Phase 3 study testing Crotalinae (pit viper) equine immune F(ab)2 and Crotalidae Polyvalent Immune Fab, ovine in people with Snake Bite, run by Instituto Bioclon S.A. de C.V. at 18 sites in United States.
Trial summary
The purpose of this study is to establish if F(ab)2 antivenom (Anavip) is safe for crotalinae envenomation. Confirm its effectiveness in preventing the occurrence of delayed coagulopathies and compare the safety and efficacy with Fab antivenom (CroFab) in patients with Crotalinae envenomation. Read more about this study
- Who is it for?
- Ages 2 to 80 years
- Conditions the study is for
- Snake Bite
- What is being tested?
- Crotalinae (pit viper) equine immune F(ab)2 and Crotalidae Polyvalent Immune Fab, ovine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 121 participants
- Where
- 18 sitesUnited States
- Study dates
- May 2008to Jan 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 2 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Men and women 2 to 80 years of age
- Presenting for emergency treatment of pit viper bite
- Informed consent document read and signed by patient (or parent/legal guardian)
Who cannot join
- Current use of any antivenom, or use within the last month
- Current participation in a clinical drug study, or participation within the last month
- Positive urine or blood pregnancy test at screening
- Breast-feeding
- Allergy to horse serum, sheep serum, or papaya
- Underlying medical conditions that significantly alter platelet count or fibrinogen; thrombocytopenia, hemophilia, familial dysfibrinogenemia, leukemia
- Use of any medication expected to affect platelet count, coagulation factors or fibrinogen: chemotherapeutic agents, warfarin, heparin
- No clinical indications of snake bite requiring antivenom for treatment
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United States18 sites
The University of New Mexico Hospital
Albuquerque, New Mexico, 87106
St. Joseph Regional Health Center
Bryan, Texas, 77802
West Texas Regional Poison Center at Thomason Hospital
El Paso, Texas, 79905
Pitt County Memorial Hospital
Greenville, North Carolina, 27834
Florida Poison Information Center
Jacksonsville, Florida, 32209
The Children's Mercy Hospital
Kansas City, Missouri, 64108
Loma Linda University Medical Center
Loma Linda, California, 92354
Banner Good Samaritan Medical Center
Phoenix, Arizona, 85006
Maricopa Integrated Health System
Phoenix, Arizona, 85008
Northwest Medical Center
Phoenix, Arizona, 85741
University of California San Diego
San Diego, California, 92103
Rady Children's Hospital
San Diego, California, 92123
Sarasota Memorial Hospital
Sarasota, Florida, 34239
LSU Health Sciences Center, Lousiana Poison Control Center
Shreveport, Louisiana, 71103
Scott and White Memorial Hospital
Temple, Texas, 76508
Tucson Medical Center
Tucson, Arizona, 85712
University Physicians Hospital
Tucson, Arizona, 85713
University Medical Center
Tucson, Arizona, 85721
About this study
Official title: A Comparison of Anavip® and CroFab® in the Treatment of Patients With Crotalinae Envenomation: A Randomized, Prospective, Blinded, Controlled, Comparative, Multicenter Study
The purpose of this study is to establish if F(ab)2 antivenom (Anavip) is safe for crotalinae envenomation. Confirm its effectiveness in preventing the occurrence of delayed coagulopathies and compare the safety and efficacy with Fab antivenom (CroFab) in patients with Crotalinae envenomation.
Read the detailed description
Fewer than 200,000 crotaline envenomations occur annually in the US.Crotaline venoms contain a broad variety of toxins, venom variability and injection quantity among individual snakes and across species result in broadly variable patient presentations. Clinical consequences of crotaline envenomation include local and systemic effects, both of which may progress for hours to days.The best studied systemic consequence is coagulopathy, which may in its complexity mimic disseminated intravascular coagulation. Platelet and clotting disorders respond rapidly to administration of polyvalent antivenom.
Crotaline viper envenomation in the United States is treated with one of two licensed products: Wyeth Antivenin (Crotalidae) Polyvalent (Polyvalent), or CroFab® (antivenin Crotalidae polyvalent immune Fab, ovine). In recent years, both of these products have been in critically short supply. Use of Wyeth Polyvalent has been associated with a greater than 75% incidence of adverse reactions, including acute type 1 and delayed type 2 immune reactions.These phenomena are an inherent risk in the use of whole immunoglobulin. CroFab´s low molecular weight creates a pharmacokinetic mismatch with crotaline venom which leds to a recurrent venom effects.
Anavip is pharmacologically and pharmacokinetically different.Because of the elimination of the Fc portion of the immunoglobulin molecule, Anavip is expected to produce far fewer adverse reactions than seen with whole immunoglobulin antivenoms and unlike Fab molecules, F(ab)2 molecules exceed the size threshold for renal clearance and thus are expected to remain in circulation for a significantly longer time and substantially reduce the incidence of recurrent coagulopathy.
- Conditions
- Snake Bite
- Being tested
- Crotalinae (pit viper) equine immune F(ab)2, Crotalidae Polyvalent Immune Fab, ovine
- Keywords
- snake bite, antivenin treatment
- Medical subject headings
- Snake Bites
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Crotalinae (pit viper) equine immune F(ab)2Biological
Also called Anavip
Anavip with Anavip Maintenance Therapy
Crotalinae (pit viper) equine immune F(ab)2Biological
Also called Anavip
Anavip with Placebo Maintenance Therapy
Crotalidae Polyvalent Immune Fab, ovineBiological
Also called CroFab
CroFab with CroFab Maintenance Therapy
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Anavip with Anavip Maintenance Therapy Receives: Biological: Crotalinae (pit viper) equine immune F(ab)2 |
| Group 2 | Experimental | Anavip with Placebo Maintenance Therapy Receives: Biological: Crotalinae (pit viper) equine immune F(ab)2 |
| Group 3 | Active comparator | CroFab with CroFab Maintenance Therapy Receives: Biological: Crotalidae Polyvalent Immune Fab, ovine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence rate of patients experiencing coagulopathy during the follow-up phase of the study. Absolute Platelet levels < 150,000/mm3. Absolute Fibrinogen levels < 150 mg/dL. Clinical coagulopathy requiring additional antivenom.
Measured: Study Day 5 (±/- 1 day), Study Day 8 (±/- 1 day)
Secondary outcomes (1)
Comparison between groups of: Percentage of patients who experience venonemia. Absolute platelet level measured Lowest absolute platelet level measured Absolute fibrinogen level Lowest absolute fibrinogen level
Measured: Study Day 5 (+/- 1 day) and Study Day 8 (+/- 1 day)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2008 (estimated)
- Study startMay 2008
- Primary completionNov 2011
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Snake BiteStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto Bioclon S.A. de C.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Universidad Nacional Autonoma de Mexico, University of Arizona
- Responsible party
- Sponsor
- Investigators
- Walter García Ubbelohde, MD, Study director, Instituto Bioclon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00636116
- Sponsor's protocol ID
- YA-07/02
- Status last verified
- Jan 2012
- First submitted
- 11 Mar 2008
- Last updated
- 10 Jan 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Comparison of Anavip® and CroFab® in the Treatment of Patients With Crotalinae Envenomation: A Randomized, Prospective, Blinded, Controlled, Comparative, Multicenter Study
- ClinicalTrials.gov ID
- NCT00636116
- Acronym / sponsor ID
- YA-07/02
- Conditions
- Snake Bite
- Keywords
- snake bite, antivenin treatment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 121 participants (actual)
- Lead sponsor
- Instituto Bioclon S.A. de C.V.Industry (pharma, biotech, devices)
- Collaborators
- Universidad Nacional Autonoma de Mexico, University of Arizona
- Study start
- May 2008
- Primary completion
- Nov 2011 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 14 Mar 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to establish if F(ab)2 antivenom (Anavip) is safe for crotalinae envenomation. Confirm its effectiveness in preventing the occurrence of delayed coagulopathies and compare the safety and efficacy with Fab antivenom (CroFab) in patients with Crotalinae envenomation.
Detailed description
Fewer than 200,000 crotaline envenomations occur annually in the US.Crotaline venoms contain a broad variety of toxins, venom variability and injection quantity among individual snakes and across species result in broadly variable patient presentations. Clinical consequences of crotaline envenomation include local and systemic effects, both of which may progress for hours to days.The best studied systemic consequence is coagulopathy, which may in its complexity mimic disseminated intravascular coagulation. Platelet and clotting disorders respond rapidly to administration of polyvalent antivenom.
Crotaline viper envenomation in the United States is treated with one of two licensed products: Wyeth Antivenin (Crotalidae) Polyvalent (Polyvalent), or CroFab® (antivenin Crotalidae polyvalent immune Fab, ovine). In recent years, both of these products have been in critically short supply. Use of Wyeth Polyvalent has been associated with a greater than 75% incidence of adverse reactions, including acute type 1 and delayed type 2 immune reactions.These phenomena are an inherent risk in the use of whole immunoglobulin. CroFab´s low molecular weight creates a pharmacokinetic mismatch with crotaline venom which leds to a recurrent venom effects.
Anavip is pharmacologically and pharmacokinetically different.Because of the elimination of the Fc portion of the immunoglobulin molecule, Anavip is expected to produce far fewer adverse reactions than seen with whole immunoglobulin antivenoms and unlike Fab molecules, F(ab)2 molecules exceed the size threshold for renal clearance and thus are expected to remain in circulation for a significantly longer time and substantially reduce the incidence of recurrent coagulopathy.
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 |
|---|---|---|
| Group 1 | Experimental | Biological: Crotalinae (pit viper) equine immune F(ab)2Anavip with Anavip Maintenance Therapy |
| Group 2 | Experimental | Biological: Crotalinae (pit viper) equine immune F(ab)2Anavip with Placebo Maintenance Therapy |
| Group 3 | Active comparator | Biological: Crotalidae Polyvalent Immune Fab, ovineCroFab with CroFab Maintenance Therapy |
Who may qualify
- Ages
- 2 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Men and women 2 to 80 years of age
- Presenting for emergency treatment of pit viper bite
- Informed consent document read and signed by patient (or parent/legal guardian)
Key exclusion criteria (8 listed)
- Current use of any antivenom, or use within the last month
- Current participation in a clinical drug study, or participation within the last month
- Positive urine or blood pregnancy test at screening
- Breast-feeding
- Allergy to horse serum, sheep serum, or papaya
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 |
|---|---|---|
| Crotalinae (pit viper) equine immune F(ab)2Also: AnavipAnavip with Anavip Maintenance Therapy | Biological | Group 1 |
| Crotalinae (pit viper) equine immune F(ab)2Also: AnavipAnavip with Placebo Maintenance Therapy | Biological | Group 2 |
| Crotalidae Polyvalent Immune Fab, ovineAlso: CroFabCroFab with CroFab Maintenance Therapy | Biological | Group 3 |
Primary outcome
Incidence rate of patients experiencing coagulopathy during the follow-up phase of the study. Absolute Platelet levels < 150,000/mm3. Absolute Fibrinogen levels < 150 mg/dL. Clinical coagulopathy requiring additional antivenom.
Time frame: Study Day 5 (±/- 1 day), Study Day 8 (±/- 1 day)
1 secondary outcome
Comparison between groups of: Percentage of patients who experience venonemia. Absolute platelet level measured Lowest absolute platelet level measured Absolute fibrinogen level Lowest absolute fibrinogen level
Time frame: Study Day 5 (+/- 1 day) and Study Day 8 (+/- 1 day)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2012.
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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.
Walter García Ubbelohde, MD study director
Instituto Bioclon
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Crotalinae (pit viper) equine immune F(ab)2 and Crotalidae Polyvalent Immune Fab, ovine in people with Snake Bite, run by Instituto Bioclon S.A. de C.V. at 18 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 3 inclusion and 8 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: finished, as of the sponsor's last update on 10 Jan 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence rate of patients experiencing coagulopathy during the follow-up phase of the study. Absolute Platelet levels < 150,000/mm3. Absolute Fibrinogen levels < 150 mg/dL. Clinical coagulopathy requiring additional antivenom. (time frame: Study Day 5 (±/- 1 day), Study Day 8 (±/- 1 day)). 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 10 Jan 2012.