Testing the effects of mass drug administration of azithromycin on mortality and other outcomes among 1–11-month-old infants in Mali (LAKANA): study protocol for a cluster-randomized, placebo-controlled, double-blinded, parallel-group, three-arm clinical trial

Trials

Study Protocol

Lotta Hallamaa¹  Taru Vehmasto¹  Laura Adubra¹  Rikhard Ihamuotila¹  Tiia Haapaniemi¹  Juho Luoma¹  Ulla Ashorn¹  Yue-Mei Fan¹  Riku Elovainio¹  Per Ashorn²  Yin Bun Cheung³  Fatoumata Diallo⁴  Samba Sow⁴  Fadima Haidara⁴  Dagmar Alber⁵  Lily Gates⁵  Nigel Klein⁵  Elaine Cloutman-Green⁵  Camilla Ducker⁶  Gwydion Gruffudd⁶  Owen Martell⁶ 

[1] Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland;Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland;Department of Paediatrics, Tampere University Hospital, Tampere, Finland;Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland;Program in Health Services and Systems Research and Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore, Singapore;Center for Vaccine Development, Bamako, Mali;Great Ormond Street Institute of Child Health, University College London, London, UK;Tro Da Ltd, London, UK;

关键词: Randomized controlled trial;    Infant;    Antibiotic;    Azithromycin;    Placebo;    Mortality;    Morbidity;    Growth;    Infection;    Inflammation;    Antimicrobial resistance;   

DOI  :  10.1186/s13063-022-06966-7

 received in 2022-10-12, accepted in 2022-11-28,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundMass drug administration (MDA) of azithromycin (AZI) has been shown to reduce under-5 mortality in some but not all sub-Saharan African settings. A large-scale cluster-randomized trial conducted in Malawi, Niger, and Tanzania suggested that the effect differs by country, may be stronger in infants, and may be concentrated within the first 3 months after treatment. Another study found no effect when azithromycin was given concomitantly with seasonal malaria chemoprevention (SMC). Given the observed heterogeneity and possible effect modification by other co-interventions, further trials are needed to determine the efficacy in additional settings and to determine the most effective treatment regimen.MethodsLAKANA stands for Large-scale Assessment of the Key health-promoting Activities of two New mass drug administration regimens with Azithromycin. The LAKANA trial is designed to address the mortality and health impacts of 4 or 2 annual rounds of azithromycin MDA delivered to 1–11-month-old (29–364 days) infants, in a high-mortality and malaria holoendemic Malian setting where there is a national SMC program. Participating villages (clusters) are randomly allocated in a ratio of 3:2:4 to three groups: placebo (control):4-dose AZI:2-dose AZI. The primary outcome measured is mortality. Antimicrobial resistance (AMR) will be monitored closely before, during, and after the intervention and both among those receiving and those not receiving MDA with the study drugs. Other outcomes, from a subset of villages, comprise efficacy outcomes related to morbidity, growth and nutritional status, outcomes related to the mechanism of azithromycin activity through measures of malaria parasitemia and inflammation, safety outcomes (AMR, adverse and serious adverse events), and outcomes related to the implementation of the intervention documenting feasibility, acceptability, and economic aspects. The enrolment commenced in October 2020 and is planned to be completed by the end of 2022. The expected date of study completion is December 2024.DiscussionIf LAKANA provides evidence in support of a positive mortality benefit resulting from azithromycin MDA, it will significantly contribute to the options for successfully promoting child survival in Mali, and elsewhere in sub-Saharan Africa.Trial registrationClinicalTrials.gov NCT04424511. Registered on 11 June 2020.

【 授权许可】

CC BY   
© The Author(s) 2023

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