Mass Azithromycin Distribution to Prevent Child Mortality in Burkina Faso: The CHAT Randomized Clinical Trial

Abstract

Importance: 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.

Objective: To evaluate the efficacy of twice-yearly azithromycin to reduce mortality in children in the presence of seasonal malaria chemoprevention.

Design, setting, and participants: 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.

Interventions: 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.

Main outcomes and measures: The primary outcome was all-cause childhood mortality, measured during a twice-yearly enumerative census.

Results: 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.

Conclusions and relevance: 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.

Trial registration: ClinicalTrials.gov Identifier: NCT03676764.

Figure 1.. Cluster and Participant Flow in a Study of Mass Azithromycin Distribution

^aAll communities in the Nouna district in Burkina Faso were eligible for inclusion and all were randomized. Randomization was stratified by whether the community was in an existing Health and Demographic Surveillance Site and selected for morbidity monitoring (n = 48) or not (n = 293). ^bMonth ranges of follow-up indicate the census period of the study: August 2019 to January 2020, February to July 2020, August 2020 to January 2021, February to July 2021, August 2021 to January 2022, and February to July 2022. The final study census occurred from August 2022 to February 2023.

Figure 2.. Map of Study Clusters by Treatment and Number of Completed Census Visits

Figure 3.. All-Cause Mortality Rates by Treatment Group

^aPermutation P value with 10 000 replicates, using the log(IRR) between groups as the test statistic.