A Phase 3 interventional study of Placebo and Azithromycin in Mortality, sponsored by Tampere University. Completed at 1 site in Mali. Open to participants aged 29 Days to 364 Days, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-05-21.
Sponsored by Tampere University · Phase 3, Interventional, and Treatment
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.
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:
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:
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).
On a cluster (village) level:
On a household level (for trial enrollment):
On a child level (for receiving study medication):
Exclusion Criteria:
On child level (for not receiving study medication):
Placebo mixture will be administered as a single dose in oral suspension form for children 1-11 months of age: 1. Single-dose of 0.5 ml / kg child weight 2. Participating households within villages allocated to this group will be visited quarterly (at 3-month intervals), for nine times. At the first eight of these visits, 1-11 month old eligible infants, for whom there is a consent for study drug provision, will be weighed and given a single dose of placebo mixture.
Drug: Placebo
Azithromycin or placebo will be administered as a single dose in oral suspension form for children 1-11 months of age: 1. Single-dose of 0.5 ml / kg child weight 2. Participating households within villages allocated to this group will be visited quarterly (at 3-month intervals), for nine times. At the first eight of these visits, 1-11 month old eligible infants, for whom there is a consent for study drug provision, will be weighed and given a single dose of study drug. 3. Azithromycin will be given at quarterly visits between January and June, and Placebo mixture will be given at quarterly visits between July and December. Azithromycin dose will be 20 mg / kg.
Drug: Placebo · Drug: Azithromycin
Azithromycin will be administered as a single dose in oral suspension form for children 1-11 months of age: 1. Single-dose of 0.5 ml (20 mg) / kg child weight. 2. Participating households within villages allocated to this group will be visited quarterly (at 3-month intervals), for nine times. At the first eight of these visits, 1-11 month old eligible infants, for whom there is a consent for study drug provision, will be weighed and given a single dose of azithromycin.
Drug: Azithromycin
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.
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.
Mortality
Mortality rate (deaths per 1,000 years at risk) among children 1-11 months of age.
Time frame: 3-month time interval (total of 8 intervals per cluster)
Morbidity
Morbidity (14-day period prevalence of fever with respiratory symptoms (ARI), fever without respiratory symptoms (malaria), and diarrhea) in children aged 4-14 months assessed in each participating cluster (village) from the secondary outcome sample.
Time frame: 3-month time interval (total of 8 intervals per cluster)
Length-for-age Z-score
Length-for-age Z-score in 6-8 and 12-14 months old children from the secondary outcome sample. Length measures will be taken at 15, 18, 21, and 24 months after the enrollment of the village into the trial. Length-for-age Z-score will be calculated using the WHO Child Growth Standards.
Time frame: 3-month time interval (total of 3 intervals per cluster)
Length
Attained length in cm in 6-8 and 12-14 months old children from the secondary outcome sample. Length measures will be taken at 15, 18, 21, and 24 months after the enrollment of the village into the trial.
Time frame: 3-month time interval (total of 3 intervals per cluster)
Weight
Attained weight in grams in 6-8 and 12-14 months old children from the secondary outcome sample. Weight measures will be taken at 15, 18, 21, and 24 months after the enrollment of the village into the trial.
Time frame: 3-month time interval (total of 3 intervals per cluster)
Weight-for age Z-score
Weight-for age Z-score in 6-8 and 12-14 months old children from the secondary outcome sample. Weight measures will be taken at 15, 18, 21, and 24 months after the enrollment of the village into the trial. Weight-for-age Z-score will be calculated using the WHO Child Growth Standards.
Time frame: 3-month time interval (total of 3 intervals per cluster)
Weight-for-length Z-score
Weight-for-length Z-score in 6-8 and 12-14 months old children from the secondary outcome sample. Length and weight measures will be taken at 15, 18, 21, and 24 months after the enrollment of the village into the trial. Weight-for-length Z score will be calculated using the WHO Child Growth Standards.
Time frame: 3-month time interval (total of 3 intervals per cluster)
Mid-upper arm circumference
Mid-upper arm circumference in 6-8 and 12-14 months old children from the secondary outcome sample. Measures will be taken at 15, 18, 21, and 24 months after the enrollment of the village into the trial.
Time frame: 3-month time interval (total of 3 intervals per cluster)
Percentage of moderate or severe stunting
Percentage of moderate or severe stunting (length-for-age Z-score \< -2 / -3) in 6-8 and 12-14 months old children from the secondary outcome sample.
Time frame: 3-month time interval (total of 3 intervals per cluster)
Percentage of moderate or severe wasting
Percentage of moderate or severe wasting (Weight-for-length Z-score \< -2 / -3) in 6-8 and 12-14 months old children from the secondary outcome sample.
Time frame: 3-month time interval (total of 3 intervals per cluster)
Percentage of moderate or severe Underweight
Percentage of moderate or severe Underweight (Weight-for-age Z-score \< -2 / -3) in 6-8 and 12-14 months old children from the secondary outcome sample.
Time frame: 3-month time interval (total of 3 intervals per cluster)
Prevalence of phenotypic and genotypic macrolide resistance
prevalence of phenotypic azithromycin resistance among S. pneumoniae or E. coli strains isolated from 4-14-month-old children, who have received 1-4 rounds of azithromycin MDA
Time frame: 12-month time interval (total of 3 intervals per cluster)
Prevalence of phenotypic and genotypic macrolide resistance
prevalence of phenotypic azithromycin resistance among S. pneumoniae or E. coli strains isolated from 49-59-month-old children, who live in the same Malian communities but have not received azithromycin MDA
Time frame: 12-month time interval (total of 3 intervals per cluster)
Prevalence of phenotypic and genotypic macrolide resistance
prevalence of phenotypic azithromycin resistance among S. pneumoniae or E. coli strains isolated from 15-26-month-old children, who have received 1-4 rounds of azithromycin MDA and live in a village that stopped azithromycin MDA 1 year before
Time frame: 12-month time interval (total of 3 intervals per cluster)
Prevalence of phenotypic and genotypic macrolide resistance
prevalence of phenotypic azithromycin resistance among S. pneumoniae or E. coli strains isolated from 24-35-month-old children, who have received 1-4 rounds of azithromycin MDA 1 year before and who live in a village that continued azithromycin MDA
Time frame: 12-month time interval (total of 3 intervals per cluster)
Prevalence of phenotypic and genotypic AMR resistance to other "ACCESS" group antibiotics
Prevalence of phenotypic and genotypic AMR against other antibiotics categorised by the World Health Organization (WHO) into "ACCESS" group, among azithromycin-resistant E. coli strains isolated from stool samples or azithromycin-resistant S. pneumoniae strains isolated from nasopharyngeal swabs (secondary outcome sample).
Time frame: 12-month time interval (total of 3 intervals per cluster)
Blood C-reactive protein concentration
Biological samples taken from 4-11 months old infants to assess effect of azithromycin MDA on systemic inflammation (blood C-reactive protein concentration) (secondary outcome sample).
Time frame: Biological samples taken before and 14 days after the fourth MDA round, 9 months after village enrollment.
Blood malaria parasitemia and hemoglobin concentration
Biological samples taken from 4-11 months old infants to assess effect of azithromycin MDA on malaria prevalence and blood hemoglobin concentration (secondary outcome sample).
Time frame: Biological samples taken before and 14 days after the fourth MDA round, 9 months after village enrollment.
Fecal neopterin, myeloperoxidase, and alpha-1-antitrypsin concentrations
Biological samples taken from 4-11 months old infants to assess effect of azithromycin MDA on intestinal inflammation and function (secondary outcome sample).
Time frame: Biological samples taken before and 14 days after the fourth MDA round, 9 months after village enrollment.
Incidence of Adverse events
Incidence of adverse events within 14 days of study drug administration. Data collected from 4-11 months old infants at 9 months after enrollment (secondary outcome sample).
Time frame: 3-month time interval
Incidence of Serious Adverse events
Incidence of serious adverse events (Death, life-threatening event, hospitalization, and other serious events as judged by a study physician) within 14 days of study drug administration, among 1-11 months old infants.
Time frame: within 14 days after MDA round.
Mortality in children aged 12-59 month
Mortality rate (deaths per 1000 years at risk) among children who were 12-59 month old when the latest azithromycin MDA took place in their village of residence.
Time frame: 3-month time interval (total of 8 intervals per cluster)
Percentage of guardians and health care workers reporting MDA acceptable
Data collected through interviews of guardians and health care workers to assess acceptability of MDA.
Time frame: 24 months after enrollment
Percentage of the study population reached with MDA
Data collected on MDA distribution and through interviews of guardians and health care workers to assess equity of MDA.
Time frame: 24 months after enrollment
Cost and Cost-effectiveness of the intervention
Data collected on MDA distribution to assess the economic aspects of MDA.The effectiveness will be determined by the trial outcome - both the primary outcome of mortality and the secondary outcomes of morbidity and possible AMR effects. The effectiveness will be expressed in different units such as deaths averted, or disability adjusted life years (DALYs).
Time frame: 24 months after enrollment
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Individual participant data collected during the trial, after deidentification. (The details are to be determined).
Supporting information: Study protocol, Sap, Icf, Csr
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