Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Non-inferiority Trial of Two Snake Antivenoms in CAR (PAVES) (PAVES)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02694952
Recruitment Status : Withdrawn (Ministry of Health in country did not authorized the conduct of the study)
First Posted : March 1, 2016
Last Update Posted : June 2, 2017
Sponsor:
Collaborator:
Medecins Sans Frontieres, Netherlands
Information provided by (Responsible Party):
Epicentre

Brief 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.

Condition or disease Intervention/treatment Phase
Snake Bites Biological: FAV-Africa Biological: EchiTabPlus-ICP Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Double-blind, Non-inferiority Trial of Two Antivenoms for the Treatment of Snakebite With Envenoming
Estimated Study Start Date : March 2016
Actual Primary Completion Date : June 2016
Actual Study Completion Date : June 2016

Arm Intervention/treatment
Active Comparator: FAV-Africa
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.
Biological: FAV-Africa
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.

Experimental: EchiTabPlus-ICP
EchiTabPlus-ICP infusion at enrollment, and then at two and six hours after enrollment, if necessary.
Biological: EchiTabPlus-ICP
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.




Primary Outcome Measures :
  1. Number of patients needing a third dose of antivenom, needing a blood transfusion, or dying [ Time Frame: 28 days after enrolment ]

Secondary Outcome Measures :
  1. Death from any cause [ Time Frame: 28 days after enrolment ]
  2. Need for blood transfusion [ Time Frame: Will be evaluated at 2, 6, 12, and 24 hours after enrolment and at hospital discharge ]
  3. Need for third dose of antivenom [ Time Frame: Will be evaluated at 2, 6, 12, and 24 hours after enrolment and at hospital discharge ]
  4. 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 ]
    Using 20 min whole blood clotting test



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • known allergy to horses or heterologous proteins of equine origins
  • pregnancy
  • have received antivenom since the snakebite

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02694952


Sponsors and Collaborators
Epicentre
Medecins Sans Frontieres, Netherlands
Investigators
Layout table for investigator information
Study Director: Rebecca Grais, PhD Epicentre
Layout table for additonal information
Responsible Party: Epicentre
ClinicalTrials.gov Identifier: NCT02694952    
Other Study ID Numbers: EPICENTRE CAR 2016
First Posted: March 1, 2016    Key Record Dates
Last Update Posted: June 2, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Snake Bites
Bites and Stings
Poisoning
Chemically-Induced Disorders
Wounds and Injuries