Clinical Trial: Single-dose Azithromycin for the Treatment of Yaws

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 Summary:

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 b
Sponsor: Lihir Medical Centre

Current Primary Outcome: Serologic cure [ Time Frame: 6 months follow up ]

Serologic cure, defined as a decrease in the VDRL titer by at least two dilutions at six month follow-up examination, with the titer at the time of treatment used as the baseline.

In the case of primary skin lesions, complete resolution or improvement of lesions within two weeks after treatment is also required.



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • clinical cure [ Time Frame: 6 months ]
    Clinical cure (improvement 14 days after treatment, assessed by photograph comparison over the time)
  • 3 months cure rate [ Time Frame: 3 months ]
    Serological Cure rates three months after treatment


Original Secondary Outcome:

  • clinical cure [ Time Frame: 6 months ]
    • Clinical cure (improvement 14 days after treatment, assessed by photograph comparison over the time)
  • 3 months cure rate [ Time Frame: 3 months ]
    • Serological Cure rates three months after treatment


Information By: Lihir Medical Centre

Dates:
Date Received: June 23, 2011
Date Started: September 2010
Date Completion:
Last Updated: April 11, 2012
Last Verified: April 2012