Single-dose Azithromycin for the Treatment of Yaws

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