Snake BitesPAVESNCT02694952
Non-inferiority Trial of Two Snake Antivenoms in CAR (PAVES)
A study testing FAV-Africa and EchiTabPlus-ICP in people with Snake Bites, run by Epicentre.
Trial summary
Interventional, individually randomized, double (e.g. investigator and participant) blinded, parallel two-arm, non-inferiority trial to assess the efficacy of EchiTabPlus-ICP compared to FAV-Africa for the treatment of snakebite with envenoming. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Snake Bites
- What is being tested?
- FAV-Africa and EchiTabPlus-ICP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Mar 2016to Jun 2016
- Phase
- Interventional
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- present within 72 hours of snakebite
- have signs and symptoms of grade 2 envenoming (oedema beyond the elbows or knees, bleeding at site of bite, bleeding from the gums or hematuria) or grade 3 envenoming (oedema to the shoulders or hips, or serious bleeding - epistaxis, hemoptysis, gastrointestinal bleeding)
- lack of coagulation of blood at 20 minutes in a dry vacutainer tube (abnormal 20 minute WBCT)
Who cannot join
- known allergy to horses or heterologous proteins of equine origins
- pregnancy
- have received antivenom since the snakebite
About this study
Official title: Randomized, Double-blind, Non-inferiority Trial of Two Antivenoms for the Treatment of Snakebite With Envenoming
Interventional, individually randomized, double (e.g. investigator and participant) blinded, parallel two-arm, non-inferiority trial to assess the efficacy of EchiTabPlus-ICP compared to FAV-Africa for the treatment of snakebite with envenoming.
Read the detailed description
The study is designed as a randomized, double-blind, non-inferiority trial among patients suffering envenoming following snakebite in Paoua, Central African Republic. The primary aim of the study is to assess the non-inferiority of EchiTabPlus-ICP compared to FAV-Africa, at preventing a composite primary endpoint consisting of death from any cause, need for blood transfusion or need for a third dose of antivenom.
A total of 196 patients will be individually randomized in a 1:1 ratio to receive FAV-Africa or EchiTabPlus-ICP.
The first dose of intervention antivenom will be administered at study enrollment, and the need for further doses will be judged by clinical exam and the 20 minute WBCT, following the protocol. All other necessary medical care will be provided as per routine in the Paoua Prefectural Hospital. Study followup and surveillance for adverse events and serious adverse events will continue until 28 days after the initial dose of antivenom.
Unique identification numbers will be allocated by an individual independent of the study team using a computer-generated random number list using permuted blocks of random sizes. Block sizes will not be disclosed to reduce predictability of the random sequence and ensure allocation concealment. The Site Principal Investigator who will oversee randomization will be given a set of sequentially numbered silver coated booklets. The Site Principal Investigator will be instructed to assign the next sequential randomization code noted in the booklet to each eligible participant as (s)he is enrolled.
Study antivenoms will be prepared by the unblinded study pharmacist, and will be provided to the clinical staff in identical presentations. Group assignment will remain concealed from study personnel, investigators, and participants for the entire study period. The Data and Safety Monitoring Board (DSMB) will also be masked to the group assignment. The DSMB will remain masked unless otherwise deemed necessary by the DSMB members for any safety related issues. Investigators conducting the final analysis will remain masked to the group assignment until the end of the analysis.
- Conditions
- Snake Bites
- Being tested
- FAV-Africa, EchiTabPlus-ICP
- Medical subject headings
- Snake Bites
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FAV-AfricaBiological
Polyspecific antivenom immunoglobulin F(ab)'2 fragments of equine origin manufactured by Sanofi Pasteur, S.A., Lyon, France. Per undiluted 1 ml, the multivalent serum contains ≥25 times the LD50 for mice exposed to venom of Bitis gabonica, Bitis arietans, Echis leucogaster, Echis ocellatus, Naja haje, Dendroaspis polylepis, Dendroaspis viridis, and Dendroaspis jamesoni, as well as ≥20 times the LD50 for mice exposed to venom of Naja melanoleuca and Naja nigricollis.
EchiTabPlus-ICPBiological
Polyspecific antivenom immunoglobulin of equine origin manufactured by the Clodomiro Picado Institute, San Jose, Costa Rica. Each 10 ml of undiluted antivenom contains enough antibody fragments to neutralize 30 mg of Echis ocellatus venom, 20 mg of Bitis arietans venom and 5 mg of Naga nigricollis venom.
| Study group | Role | What they receive |
|---|---|---|
| FAV-Africa | Active comparator | FAV-Africa infusion at enrollment, and then at two and six hours after enrollment, if necessary. To be given as unblinded rescue dose at twelve hours if fourth dose of antivenom necessary. Receives: Biological: FAV-Africa |
| EchiTabPlus-ICP | Experimental | EchiTabPlus-ICP infusion at enrollment, and then at two and six hours after enrollment, if necessary. Receives: Biological: EchiTabPlus-ICP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients needing a third dose of antivenom, needing a blood transfusion, or dying
Measured: 28 days after enrolment
Secondary outcomes (4)
Death from any cause
Measured: 28 days after enrolment
Need for blood transfusion
Measured: Will be evaluated at 2, 6, 12, and 24 hours after enrolment and at hospital discharge
Need for third dose of antivenom
Measured: Will be evaluated at 2, 6, 12, and 24 hours after enrolment and at hospital discharge
Normalization of coagulopathy as measured by the 20 minute whole blood clotting test
Using 20 min whole blood clotting test
Measured: Will be evaluated at 2, 6, 12, and 24 hours after enrolment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2016 (estimated)
- Study startMar 2016 (estimated)
- Primary completionJun 2016
- Study completionJun 2016
Why it stopped: Ministry of Health in country did not authorized the conduct of the study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Snake BitesStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Epicentre
- Sponsor type
- University, hospital or other
- Collaborators
- Medecins Sans Frontieres, Netherlands
- Responsible party
- Sponsor
- Investigators
- Rebecca Grais, PhD, Study director, Epicentre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02694952
- Sponsor's protocol ID
- EPICENTRE CAR 2016
- Acronym
- PAVES
- Status last verified
- Jun 2017
- First submitted
- 17 Feb 2016
- Last updated
- 2 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double-blind, Non-inferiority Trial of Two Antivenoms for the Treatment of Snakebite With Envenoming
- ClinicalTrials.gov ID
- NCT02694952
- Acronym / sponsor ID
- PAVES / EPICENTRE CAR 2016
- Conditions
- Snake Bites
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Ministry of Health in country did not authorized the conduct of the study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- EpicentreUniversity, hospital or other
- Collaborators
- Medecins Sans Frontieres, Netherlands
- Study start
- Mar 2016 (estimated)
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 1 Mar 2016 (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.
Interventional, individually randomized, double (e.g. investigator and participant) blinded, parallel two-arm, non-inferiority trial to assess the efficacy of EchiTabPlus-ICP compared to FAV-Africa for the treatment of snakebite with envenoming.
Detailed description
The study is designed as a randomized, double-blind, non-inferiority trial among patients suffering envenoming following snakebite in Paoua, Central African Republic. The primary aim of the study is to assess the non-inferiority of EchiTabPlus-ICP compared to FAV-Africa, at preventing a composite primary endpoint consisting of death from any cause, need for blood transfusion or need for a third dose of antivenom.
A total of 196 patients will be individually randomized in a 1:1 ratio to receive FAV-Africa or EchiTabPlus-ICP.
The first dose of intervention antivenom will be administered at study enrollment, and the need for further doses will be judged by clinical exam and the 20 minute WBCT, following the protocol. All other necessary medical care will be provided as per routine in the Paoua Prefectural Hospital. Study followup and surveillance for adverse events and serious adverse events will continue until 28 days after the initial dose of antivenom.
Unique identification numbers will be allocated by an individual independent of the study team using a computer-generated random number list using permuted blocks of random sizes. Block sizes will not be disclosed to reduce predictability of the random sequence and ensure allocation concealment. The Site Principal Investigator who will oversee randomization will be given a set of sequentially numbered silver coated booklets. The Site Principal Investigator will be instructed to assign the next sequential randomization code noted in the booklet to each eligible participant as (s)he is enrolled.
Study antivenoms will be prepared by the unblinded study pharmacist, and will be provided to the clinical staff in identical presentations. Group assignment will remain concealed from study personnel, investigators, and participants for the entire study period. The Data and Safety Monitoring Board (DSMB) will also be masked to the group assignment. The DSMB will remain masked unless otherwise deemed necessary by the DSMB members for any safety related issues. Investigators conducting the final analysis will remain masked to the group assignment until the end of the analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FAV-Africa | Active comparator | Biological: FAV-AfricaFAV-Africa infusion at enrollment, and then at two and six hours after enrollment, if necessary. To be given as unblinded rescue dose at twelve hours if fourth dose of antivenom necessary. |
| EchiTabPlus-ICP | Experimental | Biological: EchiTabPlus-ICPEchiTabPlus-ICP infusion at enrollment, and then at two and six hours after enrollment, if necessary. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- present within 72 hours of snakebite
- have signs and symptoms of grade 2 envenoming (oedema beyond the elbows or knees, bleeding at site of bite, bleeding from the gums or hematuria) or grade 3 envenoming (oedema to the shoulders or hips, or serious bleeding - epistaxis, hemoptysis, gastrointestinal bleeding)
- lack of coagulation of blood at 20 minutes in a dry vacutainer tube (abnormal 20 minute WBCT)
Key exclusion criteria (3 listed)
- known allergy to horses or heterologous proteins of equine origins
- pregnancy
- have received antivenom since the snakebite
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 |
|---|---|---|
| FAV-AfricaPolyspecific antivenom immunoglobulin F(ab)'2 fragments of equine origin manufactured by Sanofi Pasteur, S.A., Lyon, France. Per undiluted 1 ml, the multivalent serum contains ≥25 times the LD50 for mice exposed to venom of Bitis gabonica, Bitis arietans, Echis leucogaster, Echis ocellatus, Naja haje, Dendroaspis polylepis, Dendroaspis viridis, and Dendroaspis jamesoni, as well as ≥20 times the LD50 for mice exposed to venom of Naja melanoleuca and Naja nigricollis. | Biological | FAV-Africa |
| EchiTabPlus-ICPPolyspecific antivenom immunoglobulin of equine origin manufactured by the Clodomiro Picado Institute, San Jose, Costa Rica. Each 10 ml of undiluted antivenom contains enough antibody fragments to neutralize 30 mg of Echis ocellatus venom, 20 mg of Bitis arietans venom and 5 mg of Naga nigricollis venom. | Biological | EchiTabPlus-ICP |
Primary outcome
Number of patients needing a third dose of antivenom, needing a blood transfusion, or dying
Time frame: 28 days after enrolment
4 secondary outcomes
Death from any cause
Time frame: 28 days after enrolment
Need for blood transfusion
Time frame: Will be evaluated at 2, 6, 12, and 24 hours after enrolment and at hospital discharge
Need for third dose of antivenom
Time frame: Will be evaluated at 2, 6, 12, and 24 hours after enrolment and at hospital discharge
Normalization of coagulopathy as measured by the 20 minute whole blood clotting test
Time frame: Will be evaluated at 2, 6, 12, and 24 hours after enrolment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2017.
- Individual participant dataSharing planned: No
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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.
Rebecca Grais, PhD study director
Epicentre
Questions about this trial
What is this clinical trial studying?
A study testing FAV-Africa and EchiTabPlus-ICP in people with Snake Bites, run by Epicentre.
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 3 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: withdrawn, as of the sponsor's last update on 2 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Number of patients needing a third dose of antivenom, needing a blood transfusion, or dying (time frame: 28 days after enrolment). 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 2 Jun 2017.