Yaws Clinical Trial
Official title:
Single-dose Azithromycin Versus Penicillin G Benzathine for the Treatment of Yaws in Children
Yaws, an endemic treponematosis and as such a neglected tropical disease (NTD), is currently
making a comeback in children in rural areas. Injectable long acting penicillin remains the
drug of choice for the treatment of yaws. However, on the basis of successful experience
with venereal syphilis in large-scale studies, oral azithromycin has emerged as a potential
alternative that overcomes the major medical and logistic disadvantages of the current
regimen.
In this non-inferiority randomized clinical trial the investigators propose a comparable
scheme for the treatment of yaws, to test the efficacy of a single, oral dose of
azithromycin versus a single, i.m. dose of benzathine penicillin G.Sample size has been
calculated to detect a non-inferiority margin of 10%. Children < 15 years of age with a
confirmed diagnosis of yaws will be randomly assigned to receive 30mg/Kg (maximum 2g) of
azithromycin orally or 50.000units/Kg (maximum 2.4MU) of penicillin-G-benzathine
intramuscularly. The primary outcome is treatment efficacy, with cure defined serologically
(a decline in the VDRL titer of at least two dilutions by six months after treatment) and,
in primary yaws, also by epithelialization of ulcers within two weeks.
Regulatory status: Investigational - Randomized Clinical Trial. Registered product for
antibacterial therapy
BACKGROUND Penicillin remains the drug of choice for the treatment of endemic treponematoses
including yaws. This type of treatment is effective and cheap. There are, however, some
disadvantages: the pain associated with a large volume (4 ml) deep i.m. injection, a high
prevalence of self-reported allergy to penicillin, structural and logistic problems related
to a treatment based on injection of drugs.
Azithromycin, a macrolide antibiotic with a long (68 hours) half-life in tissue and proven
efficacy against T.pallidum is a promising candidate. In two randomized trials, for the
treatment of syphilis in adults, a single 2-g oral dose of azithromycin achieved cure rates
equivalent to that of standard treatment with 2.4 MU of penicillin G benzathine. On the
basis of experience with venereal syphilis, azithromycin has emerged as an alternative
treatment for Yaws. It represents a more accessible treatment as it could be prescribed by
village health workers and therefore enable yaws control to be more easily incorporated into
other primary health-care programmes.
The product is available as an oral tablet to be administered at a single dose of 30mg/Kg in
children and 2 g in adults. Safety and efficacy using azithromycin 30 mg/kg given as a
single dose in the treatment of pediatric patients over 6 months of age with otitis media
have been established and approved by the FDA.
INFORMED CONSENT All participants (or their guardian or parents) who are eligible for
enrolment in the trial according to biological and demographic inclusion criteria are
provided with detailed information on the purpose of the trial and on risks and benefits of
participation, according to information listed in an information sheet. Consent is provided
in writing.
SAMPLE SIZE JUSTIFICATION
The sample size would be 244; It was calculated on the basis of a non-inferiority trial
design and the following assumptions:
Statistical power of 80 percent;to exclude the possibility that the absolute efficacy of
azithromycin was at least 10% percent less than that of penicillin; 5% significance level
using a one-sided equivalence test of proportions; assuming that the true efficacy of each
agent was equivalent at 95 percent and that approximately 10 percent of participants would
be lost to follow-up.
RANDOMIZATION PROCEDURE A random allocation schedule, stratified according to study group,
will be generated centrally with the use of blocked randomization, random permuted blocks of
four, and a 1:1 allocation ratio. The allocation will be concealed from investigators
through the use of sequentially numbered, sealed envelopes
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
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