PDF(Pubmed)
Abstract：
Repeated mass distribution of azithromycin has been shown to reduce childhood mortality by 14% in sub-Saharan Africa. However, the estimated effect varied by location, suggesting that the intervention may not be effective in different geographical areas, time periods, or conditions.
To evaluate the efficacy of twice-yearly azithromycin to reduce mortality in children in the presence of seasonal malaria chemoprevention.
This cluster randomized placebo-controlled trial evaluating the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality included 341 communities in the Nouna district in rural northwestern Burkina Faso. Participants were children aged 1 to 59 months living in the study communities.
Communities were randomized in a 1:1 ratio to receive oral azithromycin or placebo distribution. Children aged 1 to 59 months were offered single-dose treatment twice yearly for 3 years (6 distributions) from August 2019 to February 2023.
The primary outcome was all-cause childhood mortality, measured during a twice-yearly enumerative census.
A total of 34 399 children (mean [SD] age, 25.2 [18] months) in the azithromycin group and 33 847 children (mean [SD] age, 25.6 [18] months) in the placebo group were included. A mean (SD) of 90.1% (16.0%) of the censused children received the scheduled study drug in the azithromycin group and 89.8% (17.1%) received the scheduled study drug in the placebo group. In the azithromycin group, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years). In the placebo group, 588 deaths were recorded over 58 547 person-years (10.0 deaths/1000 person-years). The incidence rate ratio for mortality was 0.82 (95% CI, 0.67-1.02; P = .07) in the azithromycin group compared with the placebo group. The incidence rate ratio was 0.99 (95% CI, 0.72-1.36) in those aged 1 to 11 months, 0.92 (95% CI, 0.67-1.27) in those aged 12 to 23 months, and 0.73 (95% CI, 0.57-0.94) in those aged 24 to 59 months.
Mortality in children (aged 1-59 months) was lower with biannual mass azithromycin distribution in a setting in which seasonal malaria chemoprevention was also being distributed, but the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference.
ClinicalTrials.gov Identifier: NCT03676764.
To evaluate the efficacy of twice-yearly azithromycin to reduce mortality in children in the presence of seasonal malaria chemoprevention.
This cluster randomized placebo-controlled trial evaluating the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality included 341 communities in the Nouna district in rural northwestern Burkina Faso. Participants were children aged 1 to 59 months living in the study communities.
Communities were randomized in a 1:1 ratio to receive oral azithromycin or placebo distribution. Children aged 1 to 59 months were offered single-dose treatment twice yearly for 3 years (6 distributions) from August 2019 to February 2023.
The primary outcome was all-cause childhood mortality, measured during a twice-yearly enumerative census.
A total of 34 399 children (mean [SD] age, 25.2 [18] months) in the azithromycin group and 33 847 children (mean [SD] age, 25.6 [18] months) in the placebo group were included. A mean (SD) of 90.1% (16.0%) of the censused children received the scheduled study drug in the azithromycin group and 89.8% (17.1%) received the scheduled study drug in the placebo group. In the azithromycin group, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years). In the placebo group, 588 deaths were recorded over 58 547 person-years (10.0 deaths/1000 person-years). The incidence rate ratio for mortality was 0.82 (95% CI, 0.67-1.02; P = .07) in the azithromycin group compared with the placebo group. The incidence rate ratio was 0.99 (95% CI, 0.72-1.36) in those aged 1 to 11 months, 0.92 (95% CI, 0.67-1.27) in those aged 12 to 23 months, and 0.73 (95% CI, 0.57-0.94) in those aged 24 to 59 months.
Mortality in children (aged 1-59 months) was lower with biannual mass azithromycin distribution in a setting in which seasonal malaria chemoprevention was also being distributed, but the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference.
ClinicalTrials.gov Identifier: NCT03676764.
摘要：
■在撒哈拉以南非洲地区，重复大量分配阿奇霉素可使儿童死亡率降低14％。然而,估计的效果因地点而异，表明干预可能在不同的地理区域无效，时间段,或条件。
■评估在存在季节性疟疾化学预防的情况下，每年两次阿奇霉素降低儿童死亡率的功效。
这项成组随机安慰剂对照试验评估了单剂量阿奇霉素预防全因儿童死亡率的有效性，该试验包括布基纳法索西北部农村努纳区的341个社区。参与者是生活在研究社区中的1至59个月的儿童。
■社区以1:1的比例随机分配接受口服阿奇霉素或安慰剂。从2019年8月至2023年2月，1至59个月的儿童每年两次接受单剂量治疗，为期3年（6次分配）。
■主要结果是全因儿童死亡率，在每年两次的人口普查中测量。
■共有34399名儿童（平均[SD]年龄，25.2[18]个月），阿奇霉素组和33847名儿童（平均[SD]年龄，包括安慰剂组25.6[18]个月）。平均（SD）90.1％（16.0％）的人口普查儿童在阿奇霉素组中接受了预定的研究药物，在安慰剂组中89.8％（17.1％）接受了预定的研究药物。在阿奇霉素组中,记录498例死亡超过60592人年（8.2例死亡/1000人年）。在安慰剂组中，588例死亡记录超过58547人年（10.0例死亡/1000人年）。与安慰剂组相比，阿奇霉素组的死亡率为0.82（95％CI，0.67-1.02；P=.07）。1~11月龄人群发病率为0.99(95%CI,0.72~1.36),0.92（95%CI，0.67-1.27）在12至23个月的人群中，和0.73（95%CI，0.57-0.94）年龄在24至59个月。
■在季节性疟疾化学预防也在分布的环境中，每年两次的阿奇霉素大量分布的儿童（1-59个月）死亡率较低，但差异无统计学意义。该研究可能不足以检测临床相关差异。
■ClinicalTrials.gov标识符：NCT03676764。
■评估在存在季节性疟疾化学预防的情况下，每年两次阿奇霉素降低儿童死亡率的功效。
这项成组随机安慰剂对照试验评估了单剂量阿奇霉素预防全因儿童死亡率的有效性，该试验包括布基纳法索西北部农村努纳区的341个社区。参与者是生活在研究社区中的1至59个月的儿童。
■社区以1:1的比例随机分配接受口服阿奇霉素或安慰剂。从2019年8月至2023年2月，1至59个月的儿童每年两次接受单剂量治疗，为期3年（6次分配）。
■主要结果是全因儿童死亡率，在每年两次的人口普查中测量。
■共有34399名儿童（平均[SD]年龄，25.2[18]个月），阿奇霉素组和33847名儿童（平均[SD]年龄，包括安慰剂组25.6[18]个月）。平均（SD）90.1％（16.0％）的人口普查儿童在阿奇霉素组中接受了预定的研究药物，在安慰剂组中89.8％（17.1％）接受了预定的研究药物。在阿奇霉素组中,记录498例死亡超过60592人年（8.2例死亡/1000人年）。在安慰剂组中，588例死亡记录超过58547人年（10.0例死亡/1000人年）。与安慰剂组相比，阿奇霉素组的死亡率为0.82（95％CI，0.67-1.02；P=.07）。1~11月龄人群发病率为0.99(95%CI,0.72~1.36),0.92（95%CI，0.67-1.27）在12至23个月的人群中，和0.73（95%CI，0.57-0.94）年龄在24至59个月。
■在季节性疟疾化学预防也在分布的环境中，每年两次的阿奇霉素大量分布的儿童（1-59个月）死亡率较低，但差异无统计学意义。该研究可能不足以检测临床相关差异。
■ClinicalTrials.gov标识符：NCT03676764。
