Snake BitePhase 2NCT00868309
A Comparison of Crotalinae Equine Immune F(ab)2 Antivenom (Anavip) and Crotalidae Polyvalent Immune Fab,
A Phase 2 study testing Anavip and CroFab in people with Snake Bite and Blood Coagulation Disorders, run by Instituto Bioclon S.A. de C.V. at 1 site in United States.
Trial summary
This phase II study was a prospective, randomized, open-label, multi-center study in the United States, involving patients from 18 to 70 years of age, comparing Anavip (Antivenin Crotalinae [pit viper] equine immune F(ab)2; Instituto Bioclon, Mexico City, Mexico) against CroFab (Protherics Inc., Nashville, Tennessee)… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Snake Bite, Blood Coagulation Disorders
- What is being tested?
- Anavip and CroFab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2005to Feb 2007
- Phase
- Phase 2
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- men and women 18 to 70 years of age
- presenting for emergency treatment of pit viper bite
- informed consent document read and signed by subject
Who cannot join
- allergy to horse serum, sheep serum, or papaya
- current use of any antivenom, or use within the last month
- current participation in a clinical drug study, or participation within the last month
- pregnancy or breast-feeding
- underlying medical conditions that significantly alter blood coagulation: thrombocytopenia, hemophilia, familial dysfibrinogenemia, leukemia, recent ingestion of superwarfarin compounds (rat poison)
- use of any medication expected to affect platelet count, coagulation factors, or fibrinogen: chemotherapeutic agents, warfarin, heparin, aspirin
- No clinical indications of snake bite envenomation
Trial locations and contacts
1 site in 1 country.
United States1 site
Tucson snakebite investigational site
Tucson, Arizona, 85724
About this study
Official title: A Comparison of Anavip and CroFab in the Treatment of Subjects With Crotalinae (Pit Viper) Envenomation: A Randomized, Prospective, Open-Label, Controlled, Comparative, Multicenter Study
This phase II study was a prospective, randomized, open-label, multi-center study in the United States, involving patients from 18 to 70 years of age, comparing Anavip (Antivenin Crotalinae [pit viper] equine immune F(ab)2; Instituto Bioclon, Mexico City, Mexico) against CroFab (Protherics Inc., Nashville, Tennessee), the only currently approved product for treatment of Crotalinae (pit viper) envenomation in the US.
The study was designed to evaluate the hypothesis that lasting correction of snakebite induced thrombocytopenia and hypofibrinogenemia are possible following correction with F(ab)2 antivenom, by analyzing in detail the relationships among platelet count, fibrinogen, venom levels, and antivenom levels in subjects presenting with thrombocytopenia following crotaline viper envenomation. In the study we expected to see a fall in platelet count following Fab treatment, commensurate with that reported in the past. We hypothesized that following F(ab)2 treatment there would be a slower drop in post-treatment platelet counts, with a relatively higher platelet count at any given point in the follow-up period. We further hypothesized that an initial rise and later fall in platelet count would correspond with rise and fall in antivenom levels, and would be mirrored by concurrent drop and rise in levels of unbound circulating venom.
Read the detailed description
The overall objective of this Phase 2 open-label comparative study was to demonstrate that the F(ab)2 antivenom Anavip has significantly longer plasma persistence than does Fab, and that this is associated with a slower rise in venom levels and slower decline in platelet count and fibrinogen following hospital discharge of envenomated subjects. The effectiveness of F(ab)2 in preventing the recurrence of coagulopathies after the subject's discharge from hospital will indicate that, inherently, F(ab)2 antivenom has an improved safety profile relative to the Fab antivenom CroFab in treating envenomation by crotaline vipers.
Each subject was assessed for quantitative serum venom levels. Relatively few historical data exist to support the use of venom levels as a surrogate endpoint in envenomation. However, changes in venom levels have been correlated with coagulopathic effects, during both the acute phase of venom toxicity and the post treatment period of recurrent venom effect. Validation of this surrogate endpoint via correlation of venom effect with platelet count and fibrinogen level in this phase II study is intended to support future studies.
The secondary endpoints were the determination of coagulation abnormalities during the follow up period.
- Conditions
- Snake Bite, Blood Coagulation Disorders
- Being tested
- Anavip, CroFab
- Keywords
- Snake Bite, Venom and antivenom kinetics
- Medical subject headings
- Snake Bites, Blood Coagulation Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnavipBiological
Also called Antivenin Crotalinae (pit viper) equine immune F(ab)2
Anavip, 10 vials Intravenous (IV) every 2 hours until initial control has been achieved; then 3 maintenance doses of 4 vials every 6 hrs
CroFabBiological
CroFab, 5 vials Intravenous (IV) every 2 hours until initial control has been achieved; then 3 maintenance doses of 2 vials every 6 hrs
| Study group | Role | What they receive |
|---|---|---|
| Anavip | Experimental | The initial dose of study drug was administered in a total volume of 500 mL (initial doses only) IV over 30 minutes for Anavip Receives: Biological: Anavip |
| CroFab | Active comparator | The initial dose of study drug was administered in a total volume of 500 mL (initial doses only) IV over 60 minutes for CroFab, or as permitted by IV access. Receives: Biological: CroFab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Detection of Plasma Venom Levels During the Post Acute Treatment Period.
Measured: Follow up after Maintenance doses were completed. Two Weeks.
Secondary outcomes (1)
>50,000 Platelets/mm3
Thrombocytopenia during follow up period. Two weeks
Measured: Follow up after maintenance dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2009 (estimated)
- Study startJan 2005
- Primary completionAug 2006
- Study completionFeb 2007
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 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto Bioclon S.A. de C.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of Arizona
- Responsible party
- Sponsor
- Investigators
- Walter García, MD, Study director, Instituto BioclonLeslie Boyer, MD, Principal investigator, University of ArizonaAlejandro Alagón, MD, PhD, Principal investigator, Instituto de Biotecnología UNAM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00868309
- Sponsor's protocol ID
- AN-03/02
- Other IDs
- AN-03/02
- Status last verified
- Mar 2016
- First submitted
- 6 Nov 2008
- Last updated
- 18 Apr 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2016. 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 Subjects With Crotalinae (Pit Viper) Envenomation: A Randomized, Prospective, Open-Label, Controlled, Comparative, Multicenter Study
- ClinicalTrials.gov ID
- NCT00868309
- Acronym / sponsor ID
- AN-03/02
- Conditions
- Snake Bite, Blood Coagulation Disorders
- Keywords
- Snake Bite, Venom and antivenom kinetics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Instituto Bioclon S.A. de C.V.Industry (pharma, biotech, devices)
- Collaborators
- University of Arizona
- Study start
- Jan 2005
- Primary completion
- Aug 2006 (actual)
- Study completion
- Feb 2007 (actual)
- First posted
- 24 Mar 2009 (estimated)
- Results
- Posted 24 Mar 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II study was a prospective, randomized, open-label, multi-center study in the United States, involving patients from 18 to 70 years of age, comparing Anavip (Antivenin Crotalinae [pit viper] equine immune F(ab)2; Instituto Bioclon, Mexico City, Mexico) against CroFab (Protherics Inc., Nashville, Tennessee), the only currently approved product for treatment of Crotalinae (pit viper) envenomation in the US.
The study was designed to evaluate the hypothesis that lasting correction of snakebite induced thrombocytopenia and hypofibrinogenemia are possible following correction with F(ab)2 antivenom, by analyzing in detail the relationships among platelet count, fibrinogen, venom levels, and antivenom levels in subjects presenting with thrombocytopenia following crotaline viper envenomation. In the study we expected to see a fall in platelet count following Fab treatment, commensurate with that reported in the past. We hypothesized that following F(ab)2 treatment there would be a slower drop in post-treatment platelet counts, with a relatively higher platelet count at any given point in the follow-up period. We further hypothesized that an initial rise and later fall in platelet count would correspond with rise and fall in antivenom levels, and would be mirrored by concurrent drop and rise in levels of unbound circulating venom.
Detailed description
The overall objective of this Phase 2 open-label comparative study was to demonstrate that the F(ab)2 antivenom Anavip has significantly longer plasma persistence than does Fab, and that this is associated with a slower rise in venom levels and slower decline in platelet count and fibrinogen following hospital discharge of envenomated subjects. The effectiveness of F(ab)2 in preventing the recurrence of coagulopathies after the subject's discharge from hospital will indicate that, inherently, F(ab)2 antivenom has an improved safety profile relative to the Fab antivenom CroFab in treating envenomation by crotaline vipers.
Each subject was assessed for quantitative serum venom levels. Relatively few historical data exist to support the use of venom levels as a surrogate endpoint in envenomation. However, changes in venom levels have been correlated with coagulopathic effects, during both the acute phase of venom toxicity and the post treatment period of recurrent venom effect. Validation of this surrogate endpoint via correlation of venom effect with platelet count and fibrinogen level in this phase II study is intended to support future studies.
The secondary endpoints were the determination of coagulation abnormalities during the follow up period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anavip | Experimental | Biological: AnavipThe initial dose of study drug was administered in a total volume of 500 mL (initial doses only) IV over 30 minutes for Anavip |
| CroFab | Active comparator | Biological: CroFabThe initial dose of study drug was administered in a total volume of 500 mL (initial doses only) IV over 60 minutes for CroFab, or as permitted by IV access. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- men and women 18 to 70 years of age
- presenting for emergency treatment of pit viper bite
- informed consent document read and signed by subject
Key exclusion criteria (7 listed)
- allergy to horse serum, sheep serum, or papaya
- current use of any antivenom, or use within the last month
- current participation in a clinical drug study, or participation within the last month
- pregnancy or breast-feeding
- underlying medical conditions that significantly alter blood coagulation: thrombocytopenia, hemophilia, familial dysfibrinogenemia, leukemia, recent ingestion of superwarfarin compounds (rat poison)
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 |
|---|---|---|
| AnavipAlso: Antivenin Crotalinae (pit viper) equine immune F(ab)2Anavip, 10 vials Intravenous (IV) every 2 hours until initial control has been achieved; then 3 maintenance doses of 4 vials every 6 hrs | Biological | Anavip |
| CroFabCroFab, 5 vials Intravenous (IV) every 2 hours until initial control has been achieved; then 3 maintenance doses of 2 vials every 6 hrs | Biological | CroFab |
Primary outcome
Detection of Plasma Venom Levels During the Post Acute Treatment Period.
Time frame: Follow up after Maintenance doses were completed. Two Weeks.
1 secondary outcome
>50,000 Platelets/mm3
Time frame: Follow up after maintenance dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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, MD study director
Instituto Bioclon
Leslie Boyer, MD principal investigator
University of Arizona
Alejandro Alagón, MD, PhD principal investigator
Instituto de Biotecnología UNAM
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anavip and CroFab in people with Snake Bite and Blood Coagulation Disorders, run by Instituto Bioclon S.A. de C.V. at 1 site 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 7 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 18 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 24 Mar 2009). 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?
Detection of Plasma Venom Levels During the Post Acute Treatment Period. (time frame: Follow up after Maintenance doses were completed. Two Weeks.). 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 18 Apr 2016.