Francis I. Proctor Foundation, University of California, San Francisco, USA.
Centre de Recherche et Interventions en Santé Publique, Birni N'Gaoure, Niger.
BMC Public Health. 2021 Apr 29;21(1):822. doi: 10.1186/s12889-021-10824-7.
Biannual distribution of azithromycin to children 1-59 months old reduced mortality by 14% in a cluster-randomized trial. The World Health Organization has proposed targeting this intervention to the subgroup of children 1-11 months old to reduce selection for antimicrobial resistance. Here, we describe a trial designed to determine the impact of age-based targeting of biannual azithromycin on mortality and antimicrobial resistance.
AVENIR is a cluster-randomized, placebo-controlled, double-masked, response-adaptive large simple trial in Niger. During the 2.5-year study period, 3350 communities are targeted for enrollment. In the first year, communities in the Dosso region will be randomized 1:1:1 to 1) azithromycin 1-11: biannual azithromycin to children 1-11 months old with placebo to children 12-59 months old, 2) azithromycin 1-59: biannual azithromycin to children 1-59 months old, or 3) placebo: biannual placebo to children 1-59 months old. Regions enrolled after the first year will be randomized with an updated allocation based on the probability of mortality in children 1-59 months in each arm during the preceding study period. A biannual door-to-door census will be conducted to enumerate the population, distribute azithromycin and placebo, and monitor vital status. Primary mortality outcomes are defined as all-cause mortality rate (deaths per 1000 person-years) after 2.5 years from the first enrollment in 1) children 1-59 months old comparing the azithromycin 1-59 and placebo arms, 2) children 1-11 months old comparing the azithromycin 1-11 and placebo arm, and 3) children 12-59 months in the azithromycin 1-11 and azithromycin 1-59 arms. In the Dosso region, 50 communities from each arm will be followed to monitor antimicrobial resistance. Primary resistance outcomes will be assessed after 2 years of distributions and include 1) prevalence of genetic determinants of macrolide resistance in nasopharyngeal samples from children 1-59 months old, and 2) load of genetic determinants of macrolide resistance in rectal samples from children 1-59 months old.
As high-mortality settings consider this intervention, the results of this trial will provide evidence to support programmatic and policy decision-making on age-based strategies for azithromycin distribution to promote child survival.
This trial was registered on January 13, 2020 (clinicaltrials.gov: NCT04224987 ).
在一项整群随机试验中，给 1-59 月龄儿童每 6 个月服用一次阿奇霉素可使死亡率降低 14%。世界卫生组织建议将该干预措施针对 1-11 月龄儿童亚组，以减少对抗微生物药物耐药性的选择。在此，我们描述了一项旨在确定基于年龄的每 6 个月使用阿奇霉素方案对死亡率和抗微生物药物耐药性的影响的试验。
AVENIR 是在尼日尔进行的一项整群随机、安慰剂对照、双盲、反应适应性大简单试验。在 2.5 年的研究期间，将有 3350 个社区作为目标进行入组。在第一年，多索地区的社区将按 1:1:1 的比例随机分为 1）阿奇霉素 1-11：每 6 个月给 1-11 月龄儿童服用阿奇霉素，给 12-59 月龄儿童服用安慰剂；2）阿奇霉素 1-59：每 6 个月给 1-59 月龄儿童服用阿奇霉素；或 3）安慰剂：每 6 个月给 1-59 月龄儿童服用安慰剂。在第一年之后入组的地区将根据在前一研究期间每个臂 1-59 月龄儿童的死亡率概率进行更新的分配进行随机分组。将每 6 个月进行一次挨家挨户的普查，以清点人口、分发阿奇霉素和安慰剂，并监测生命状况。主要死亡率结局定义为 1）在第 2.5 年时，比较 1）阿奇霉素 1-59 臂和安慰剂臂的 1-59 月龄儿童的全因死亡率（每 1000 人年死亡人数），2）比较阿奇霉素 1-11 臂的 1-11 月龄儿童和安慰剂臂的全因死亡率，以及 3）阿奇霉素 1-11 臂和阿奇霉素 1-59 臂的 12-59 月龄儿童的全因死亡率。在多索地区，将对每个臂的 50 个社区进行随访，以监测抗微生物药物耐药性。主要耐药性结局将在 2 年的药物分发后进行评估，包括 1）来自 1-59 月龄儿童的鼻咽样本中大环内酯类耐药的遗传决定因素的流行率，以及 2）来自 1-59 月龄儿童的直肠样本中大环内酯类耐药的遗传决定因素的负荷。
在高死亡率地区考虑这种干预措施时，该试验的结果将为支持基于年龄的阿奇霉素分配方案提供证据，以促进儿童生存，从而为方案和政策决策提供依据。
该试验于 2020 年 1 月 13 日在（clinicaltrials.gov：NCT04224987）注册。
