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

Epicentre

Status: Withdrawn

Conditions: Snake Bites

Treatments: Biological: FAV-Africa; Biological: EchiTabPlus-ICP

Study type: Interventional

Funder types: Other

Identifiers

NCT02694952

EPICENTRE CAR 2016

Details and patient eligibility

About

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.

Full 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.

Sex: All

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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0 participants in 2 patient groups

FAV-Africa

Active Comparator group

Description:

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.

Treatment:

Biological: FAV-Africa

EchiTabPlus-ICP

Experimental group

Description:

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

Treatment:

Biological: EchiTabPlus-ICP