NCT04424511

Effects of Mass Drug Administration of Azithromycin on Mortality and Other Outcomes Among 1-11 Month Old Infants in Mali

LAKANA , a Cluster-randomized, Double-blinded, Parallel Group, Controlled Trial, Testing the Effects of Mass Drug Administration of Azithromycin on Mortality and Other Outcomes Among 1-11 Month Old Infants in Rural Mali.

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 149,201 (actual)
• Sponsor: Tampere University · Academic / Other
• Sex: All
• Age: 29 Days – 364 Days
• Healthy volunteers: Accepted

Summary

The LAKANA trial will assess the impact on mortality and other health outcomes of quarterly and biannual azithromycin mass drug administration (MDA) when delivered to 1-11-month (29-364 days) old infants in a high-mortality setting where malaria is holoendemic but there is also a functioning seasonal malaria chemoprevention (SMC) program in place. The long-term goal is to more precisely define the role of mass azithromycin treatments as an intervention for reducing childhood mortality, and to determine the most effective treatment regimen. The main study hypotheses in terms of mortality effect are: i) Biannual azithromycin MDA to 1-11 month old infants reduces their mortality, ii) Quarterly azithromycin MDA to 1-11 month old infants reduces their mortality, iii) Quarterly azithromycin MDA has a bigger mortality effect than biannual MDA.

Detailed description

Mass drug administration (MDA) of azithromycin has been shown to reduce under-5 mortality in some but not all sub-Saharan African settings. Because of the observed heterogeneity and possible effect modification by SMC or other co-interventions, further trials in new settings are needed in order to make evidence-based public health recommendations about the use of this treatment. The objectives of the LAKANA trial are: * To evaluate the impact of two azithromycin MDA regimens on infant mortality and other health outcomes, when provided in a rural West-African high-mortality context with an ongoing seasonal malaria chemoprevention program. * To evaluate the effect of alternative MDA frequencies on antimicrobial resistance (AMR) and host microbiota composition. * To test hypotheses that azithromycin MDA eliminates malaria parasitaemia and reduces systemic and intestinal inflammation in asymptomatic children and to collect and store biological samples for assessing other possible mechanisms of azithromycin effect. * To investigate the feasibility of alternative azithromycin MDA strategies, including economic analysis. The LAKANA trial will be conducted in 1151 villages from 7-10 health districts in the Kayes, Kita and Koulikoro regions of Mali. LAKANA is a cluster-randomized, placebo-controlled, double-blinded, parallel-group, three-arm clinical trial, with adaptive design. Participating villages will be randomly allocated to three different intervention groups in a ratio of 3 : 2 : 4 (control : azithromycin quarterly : azithromycin biannually). Within each participating village, consenting households will be visited quarterly (at 3-month intervals), nine times. At the first eight of these visits, 1-11-month-old eligible infants (age 29-364 days), for whom there is a consent for study drug provision, will be given a single dose of study drug (azithromycin mixture or respective placebo mixture). Mortality and serious adverse events (SAEs) data will be collected, and mortality-related questions answered using data from all the included 1151 villages. Mixed-effect Poisson regression model will be used to estimate the intervention effects on mortality, with random intercepts for the clusters. The investigators will explore effect modification by testing for interaction between the MDA intervention and the following variables: * Age at the time of the MDA * Sex of the child * Weight-for-age * Seasonality: rainy season vs non-rainy season at the time of the MDA * SMC given to the child within 3 months before an MDA * Order of MDA in the village * District of residence * Distance from the nearest health facility (in km) * Household asset index * Water, Sanitation, and Hygiene (WASH) index * National outreach strategy category (standard/advanced) The investigators will address the other study questions using a smaller separate secondary sample of 59 villages located around four selected health centers close to the city of Kita and a similar number of villages closer to Bamako, i.e. in Koulikoro or Kati (tertiary sample).

Conditions

• Mortality

Interventions

Type	Name	Description
DRUG	Placebo	Placebo mixture will be administered as a single dose in oral suspension form for children 1-11 months of age. Weight-based dosing will be used: single-dose of 0.5 ml / kg child weight.
DRUG	Azithromycin	Azithromycin will be administered as a single dose in oral suspension form for children 1-11 months of age. Weight-based dosing will be used: single-dose of 0.5 ml (20 mg) / kg child weight.

Timeline

• Start date: 2020-10-15
• Primary completion: 2024-12-31
• Completion: 2024-12-31
• First posted: 2020-06-11
• Last updated: 2025-05-21

Locations

1 site across 1 country: Mali