Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2023 Nov 15;24(1):733.
doi: 10.1186/s13063-023-07771-6.

Statistical analysis plan for the LAKANA trial: a cluster-randomized, placebo-controlled, double-blinded, parallel group, three-arm clinical trial testing the effects of mass drug administration of azithromycin on mortality and other outcomes among 1-11-month-old infants in Mali

Juho Luoma  1 , Laura Adubra  2 , Dagmar Alber  3 , Per Ashorn  2   4 , Ulla Ashorn  2 , Elaine Cloutman-Green  3 , Fatoumata Diallo  5 , Camilla Ducker  6 , Riku Elovainio  2 , Yue-Mei Fan  2 , Lily Gates  3 , Gwydion Gruffudd  6 , Tiia Haapaniemi  2 , Fadima Haidara  5 , Lotta Hallamaa  2 , Rikhard Ihamuotila  2 , Nigel Klein  3 , Owen Martell  6 , Samba Sow  5 , Taru Vehmasto  2 , Yin Bun Cheung  2   7
Affiliations
Randomized Controlled Trial

Statistical analysis plan for the LAKANA trial: a cluster-randomized, placebo-controlled, double-blinded, parallel group, three-arm clinical trial testing the effects of mass drug administration of azithromycin on mortality and other outcomes among 1-11-month-old infants in Mali

Juho Luoma et al. Trials. .

Abstract

Background: The Large-scale Assessment of the Key health-promoting Activities of two New mass drug administration regimens with Azithromycin (LAKANA) trial in Mali aims to evaluate the efficacy and safety of azithromycin (AZI) mass drug administration (MDA) to 1-11-month-old infants as well as the impact of the intervention on antimicrobial resistance (AMR) and mechanisms of action of azithromycin. To improve the transparency and quality of this clinical trial, we prepared this statistical analysis plan (SAP).

Methods/design: LAKANA is a cluster randomized trial that aims to address the mortality and health impacts of biannual and quarterly AZI MDA. AZI is given to 1-11-month-old infants in a high-mortality setting where a seasonal malaria chemoprevention (SMC) program is in place. The participating villages are randomly assigned to placebo (control), two-dose AZI (biannual azithromycin-MDA), and four-dose AZI (quarterly azithromycin-MDA) in a 3:4:2 ratio. The primary outcome of the study is mortality among the intention-to-treat population of 1-11-month-old infants. We will evaluate relative risk reduction between the study arms using a mixed-effects Poisson model with random intercepts for villages, using log link function with person-years as an offset variable. We will model outcomes related to secondary objectives of the study using generalized linear models with considerations on clustering.

Conclusion: The SAP written prior to data collection completion will help avoid reporting bias and data-driven analysis for the primary and secondary aims of the trial. If there are deviations from the analysis methods described here, they will be described and justified in the publications of the trial results.

Trial registration: ClinicalTrials.gov ID NCT04424511 . Registered on 11 June 2020.

Keywords: Antibiotic; Antimicrobial resistance; Azithromycin; Cluster randomized trial; Growth; Inflammation; Morbidity; Mortality; Statistical analysis plan.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
The assumptions of AMR prevalence at baseline and follow-up visits in the 4–14-month-old and 49–59-month-old children. Graph is generated with hypothetical data for illustration of what the study team hypothesizes
Fig. 2
Fig. 2
Trial profile
See this image and copyright information in PMC

References

    1. Keenan JD, Bailey RL, West SK, Arzika AM, Hart J, Weaver J, et al. Azithromycin to reduce childhood mortality in sub-Saharan Africa. N Engl J Med. 2018;378(17):1583–1592. doi: 10.1056/NEJMoa1715474. - DOI - PMC - PubMed
    1. Adubra L, Alber D, Ashorn P, Ashorn U, Cheung YB, Cloutman-Green E, et al. 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. 2023;24(1):5. doi: 10.1186/s13063-022-06966-7. - DOI - PMC - PubMed
    1. Gamble C, Krishan A, Stocken D, Lewis S, Juszczak E, Doré C, et al. Guidelines for the content of statistical analysis plans in clinical trials. JAMA. 2017;318(23):2337. doi: 10.1001/jama.2017.18556. - DOI - PubMed
    1. Institut National de la Statistique - INSTAT, Cellule de Planification et de Statistique Secteur Santé-Développement, ICF. Mali Demographic and Health Survey 2018. Bamako, Mali: INSTAT/CPS/SS-DS-PF and ICF; 2019. Available from: http://dhsprogram.com/pubs/pdf/FR358/FR358.pdf. Accessed 5 Dec 2022.
    1. WHO Multicentre growth reference study group. Onis M. WHO Child Growth Standards based on length/height, weight and age: WHO Child Growth Standards. Acta Paediatr. 2007;95:76–85. doi: 10.1111/j.1651-2227.2006.tb02378.x. - DOI - PubMed

Publication types

Associated data