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,
Laura Adubra,
Dagmar Alber,
Per Ashorn,
Ulla Ashorn,
Elaine Cloutman-Green,
Fatoumata Diallo,
Camilla Ducker,
Riku Elovainio,
Yue-Mei Fan,
Lily Gates,
Gwydion Gruffudd,
Tiia Haapaniemi,
Fadima Haidara,
Lotta Hallamaa,
Rikhard Ihamuotila,
Nigel Klein,
Owen Martell,
Samba Sow,
Taru Vehmasto,
Yin Bun Cheung
Affiliations
Juho Luoma
Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University
Laura Adubra
Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University
Dagmar Alber
Great Ormond Street Institute of Child Health, University College London
Per Ashorn
Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University
Ulla Ashorn
Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University
Elaine Cloutman-Green
Great Ormond Street Institute of Child Health, University College London
Fatoumata Diallo
Center for Vaccine Development
Camilla Ducker
Tro Da Ltd
Riku Elovainio
Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University
Yue-Mei Fan
Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University
Lily Gates
Great Ormond Street Institute of Child Health, University College London
Gwydion Gruffudd
Tro Da Ltd
Tiia Haapaniemi
Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University
Fadima Haidara
Center for Vaccine Development
Lotta Hallamaa
Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University
Rikhard Ihamuotila
Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University
Nigel Klein
Great Ormond Street Institute of Child Health, University College London
Owen Martell
Tro Da Ltd
Samba Sow
Center for Vaccine Development
Taru Vehmasto
Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University
Yin Bun Cheung
Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University
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.
