Brief Title
Single-dose Azithromycin for the Treatment of Yaws
Official Title
Single-dose Azithromycin Versus Penicillin G Benzathine for the Treatment of Yaws in Children
Brief Summary
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.
Detailed Description
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
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Serologic cure
Secondary Outcome
clinical cure
Condition
Yaws
Intervention
Penicillin-G-benzathine
Study Arms / Comparison Groups
Penicillin-G-Benzathine
Description: penicillin-G-Benzathine : 50,000 UI/Kg single dose(maximum 2.4 million units IM)
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
255
Start Date
September 2010
Completion Date
September 2011
Primary Completion Date
September 2011
Eligibility Criteria
Inclusion Criteria:
- All children 6 months to 15 years of age who present to LMC with suggestive skin
lesions or joint pains and VDRL and TPHA testing are positive
- Suggestive skin lesions defined as: Symptomatic > 4 weeks, painless, a traumatic
ulcers with raised margins. VDRL positive when titer of at least 1:16
Exclusion Criteria:
- Pregnancy
- Less than 6 months of age
- Known allergy to penicillin or macrolide
- Use of antibiotics active against treponema during the preceding six months
(penicillin-G-benzathine, ceftriaxone, azithromycin or doxycycline)
Gender
All
Ages
6 Months - 15 Years
Accepts Healthy Volunteers
No
Contacts
Quique Bassat, MD, PhD, ,
Location Countries
Papua New Guinea
Location Countries
Papua New Guinea
Administrative Informations
NCT ID
NCT01382004
Organization ID
YAWS-AZ01
Responsible Party
Principal Investigator
Study Sponsor
Lihir Medical Centre
Collaborators
Centre For International Health
Study Sponsor
Quique Bassat, MD, PhD, Study Director, Centre for International Health Research/Hospital Clínic/University of barcelona
Verification Date
April 2012