单剂量口服阿奇霉素与肌内注射苄星青霉素治疗雅司病——加纳的一项随机非劣效性试验
A Single Dose Oral Azithromycin versus Intramuscular Benzathine Penicillin for the Treatment of Yaws-A Randomized Non Inferiority Trial in Ghana.
作者信息
Kwakye-Maclean Cynthia, Agana Nsiire, Gyapong John, Nortey Priscilia, Adu-Sarkodie Yaw, Aryee Esther, Asiedu Kingsley, Ballard Roland, Binka Fred
机构信息
Ga West Municipal Health Administrations, Ghana Health Service, Amasaman, Ghana.
National Yaws Eradication Program, Ghana Health Service, Accra, Ghana.
出版信息
PLoS Negl Trop Dis. 2017 Jan 10;11(1):e0005154. doi: 10.1371/journal.pntd.0005154. eCollection 2017 Jan.
BACKGROUND
Yaws is a treponemal infection that was almost eradicated fifty years ago; however, the disease has re-emerged in a number of countries including Ghana. A single-dose of intramuscular benzathine penicillin has been the mainstay of treatment for yaws. However, intramuscular injections are painful and pose safety and logistical constraints in the poor areas where yaws occurs. A single center randomized control trial (RCT) carried out in Papua New Guinea in 2012 demonstrated the efficacy of a single-dose of oral azithromycin for the treatment of yaws. In this study, we also compared the efficacy of a single oral dose of azithromycin as an alternative to intramuscular benzathine penicillin for the treatment of the disease in another geographic setting.
METHODOLOGY
We conducted an open-label, randomized non-inferiority trial in three neighboring yaws-endemic districts in Southern Ghana. Children aged 1-15 years with yaws lesions were assigned to receive either 30mg/kg of oral azithromycin or 50,000 units/kg of intramuscular benzathine penicillin. The primary end point was clinical cure rate, defined as a complete or partial resolution of lesions 3 weeks after treatment. The secondary endpoint was serological cure, defined as at least a 4-fold decline in baseline RPR titre 6 months after treatment. Non- inferiority of azithromycin treatment was determined if the upper bound limit of a 2 sided 95% CI was less than 10%.
FINDINGS
The mean age of participants was 9.5 years (S.D.3.1, range: 1-15 years), 247(70%) were males. The clinical cure rates were 98.2% (95% CI: 96.2-100) in the azithromycin group and 96.9% (95% CI: 94.1-99.6) in the benzathine penicillin group. The serological cure rates at 6 months were 57.4% (95% CI: 49.9-64.9) in the azithromycin group and 49.1% (95% CI: 41.2-56.9) in the benzathine penicillin group, thus achieving the specified criteria for non-inferiority.
CONCLUSIONS
A single oral dose of azithromycin, at a dosage of 30mg/kg, was non-inferior to a single dose of intramuscular benzathine penicillin for the treatment of early yaws among Ghanaian patients, and provides additional support for the WHO policy for use of oral azithromycin for the eradication of yaws in resource-poor settings.
TRIAL REGISTRATION
Pan African Clinical Trials Registry PACTR2013030005181 http://www.pactr.org/.
背景
雅司病是一种螺旋体感染疾病，在五十年前几乎已被根除；然而，该疾病在包括加纳在内的一些国家再度出现。单剂量肌内注射苄星青霉素一直是雅司病治疗的主要方法。然而，肌内注射很疼，并且在雅司病流行的贫困地区存在安全和后勤方面的限制。2012年在巴布亚新几内亚进行的一项单中心随机对照试验（RCT）证明了单剂量口服阿奇霉素治疗雅司病的疗效。在本研究中，我们还在另一个地理区域比较了单剂量口服阿奇霉素作为肌内注射苄星青霉素替代品治疗该病的疗效。
方法
我们在加纳南部三个相邻的雅司病流行区进行了一项开放标签、随机非劣效性试验。年龄在1至15岁有雅司病皮损的儿童被分配接受30mg/kg口服阿奇霉素或50,000单位/kg肌内注射苄星青霉素。主要终点是临床治愈率，定义为治疗3周后皮损完全或部分消退。次要终点是血清学治愈率，定义为治疗6个月后基线快速血浆反应素（RPR）滴度至少下降4倍。如果双侧95%置信区间的上限小于10%，则确定阿奇霉素治疗的非劣效性。
结果
参与者的平均年龄为9.5岁（标准差3.1，范围：1至15岁），247名（70%）为男性。阿奇霉素组的临床治愈率为98.2%（95%置信区间：96.2 - 100），苄星青霉素组为96.9%（95%置信区间：94.1 - 99.6）。6个月时的血清学治愈率，阿奇霉素组为57.4%（95%置信区间：49.9 - 64.9），苄星青霉素组为49.1%（95%置信区间：41.2 - 56.9），从而达到了指定的非劣效性标准。
结论
对于加纳患者早期雅司病的治疗，30mg/kg剂量的单剂量口服阿奇霉素不劣于单剂量肌内注射苄星青霉素，并为世界卫生组织在资源匮乏地区使用口服阿奇霉素根除雅司病的政策提供了额外支持。
试验注册
泛非临床试验注册中心PACTR2013030（005181）http://www.pactr.org/
Zotero 插件