Single-dose Azithromycin Versus Penicillin G Benzathine for the Treatment of Yaws in Children
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 255
- 试验地点
- 1
- 主要终点
- Serologic cure
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 15 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
Penicillin-G-Benzathine
penicillin-G-Benzathine : 50,000 UI/Kg single dose(maximum 2.4 million units IM)
干预措施: Penicillin-G-benzathine (Drug)
Azithromycin
Azithromycin: 30 mg/kg single dose (Maximum: 2.000 mg.)
干预措施: Azithromycin (Drug)
结局指标
主要结局
Serologic cure
时间窗: 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.
次要结局
- 3 months cure rate(3 months)
- clinical cure(6 months)
研究者
Oriol Mitja
M.D.
Lihir Medical Centre