MortalityPhase 3LAKANANCT04424511
Effects of Mass Drug Administration of Azithromycin on Mortality and Other Outcomes Among 1-11 Month Old Infants in Mali
A Phase 3 study testing Azithromycin in people with Mortality, run by Tampere University at 1 site in Mali.
Trial 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… Read more about this study
- Who is it for?
- Ages 29 to 364 daysHealthy volunteers can take part
- Conditions the study is for
- Mortality
- What is being tested?
- Azithromycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 149,201 participants
- Where
- 1 siteMali
- Study dates
- 15 Oct 2020to 31 Dec 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 29 to 364 days
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- On a cluster (village) level:
- Location within Kayes, Kita, or Koulikoro region of Mali
- Considered accessible and safe by the local health authorities and research team
- Considered non-urban by the local health authorities and research team
- Permission from community leadership
- On a household level (for trial enrollment):
Show all 12Show fewer
- Location within a cluster that is included in the study
- Verbal consent from a head of household or an adult authorized by her / him
- On a child level (for receiving study medication):
- Residence in a household enrolled in the trial
- Age between 29 and 364 days
- Verbal consent from at least one caregiver
Who cannot join
- On child level (for not receiving study medication):
- Weight below 3.0 kg
- Known allergy to macrolides, as judged by a caregiver report of the infant experiencing an adverse reaction after oral ingestion of medication, which was deemed likely to be a macrolide by the interviewing data collector.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
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.
Read the 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
- Being tested
- Placebo, Azithromycin
- Keywords
- Mass Drug Administration, Azithromycin, Infant and Child Mortality, Infant and Child health, Infant and Child growth, Infant and Child morbidity, Antimicrobial Resistance, Feasibility, Acceptability, Safety, Cost, Inflammation, Infection
- Medical subject headings
- Inflammation, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
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.
AzithromycinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Control | Placebo comparator | 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. Receives: Drug: Placebo |
| Azithromycin-biannually (Azi-biannual) | Active comparator | 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. Receives: Drug: Placebo; Drug: Azithromycin |
| Azithromycin-quarterly | Active comparator | 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. Receives: Drug: Azithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality
Mortality rate (deaths per 1,000 years at risk) among children 1-11 months of age.
Measured: 3-month time interval (total of 8 intervals per cluster)
Secondary outcomes (24)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 24 months after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start15 Oct 2020
- Primary completion31 Dec 2024
- Study completion31 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for MortalityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- LAKANA is a cluster-randomized, placebo-controlled, double-blinded, parallel-group, three-arm clinical trial, with adaptive design.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 149,201 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tampere University
- Sponsor type
- University, hospital or other
- Collaborators
- Center for Vaccine Development CVD-Mali, Bamako, Mali, University College London Hospitals, Tro Da Ltd, UK, Duke-NUS Graduate Medical School, Bill and Melinda Gates Foundation, Pfizer Inc. (Provider of study drugs)
- Responsible party
- Principal investigator, Per Ashorn, Tampere University
- Investigators
- Per Ashorn, MD, PhD, Principal investigator, Center for Child Health Research, Tampere UniversityUlla Ashorn, PhD, Principal investigator, Center for Child Health Research, Tampere UniversitySamba Sow, MD, MSc, Principal investigator, Center for Vaccine Development CVD-MaliNigel Klein, MBBS, PhD, Principal investigator, University College London HospitalsCamilla Ducker, MBBS, MSc, Principal investigator, Tro Da Ltd, UKYin Bun Cheung, PhD, Principal investigator, Centre for Quantitative Medicine, Duke-NUS Medical SchoolDagmar Alber, PhD, Principal investigator, University College London Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04424511
- Sponsor's protocol ID
- LAKANA trial
- Other IDs
- INV-003354
- Acronym
- LAKANA
- Status last verified
- May 2025
- First submitted
- 22 May 2020
- Last updated
- 21 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data collected during the trial, after deidentification. (The details are to be determined).
Publications
Ihamuotila R, Juma J, Haidara F, Samake O, Luoma J, Adubra L, Cheung YB, Alber D, Traore A, Ducker C, Ashorn U, Ashorn P, Sow S, Fan YM. A single dose of azithromycin versus placebo for malaria in infants: A cluster-randomized trial. PLOS Glob Public Health. 2026 Aug 20;6(8):e0006518. doi: 10.1371/journal.pgph.0006518. eCollection 2026.
PubMed 42623398Adubra L, Luoma J, Fan YM, Haidara FC, Samake O, Ihamuotila R, Ylikruuvi K, Hallamaa L, Martell O, Ducker C, Alber D, Ashorn P, Cheung YB, Sow S, Ashorn U. Infant Growth After Mass Administration of Azithromycin: Secondary Outcomes of a Cluster Randomized Clinical Trial. JAMA Netw Open. 2026 Jun 1;9(6):e2617425. doi: 10.1001/jamanetworkopen.2026.17425.
PubMed 42268611Haidara FC, Adubra L, Abdou M, Alber D, Ashorn U, Cheung YB, Cloutman-Green E, Diallo M, Ducker C, Fan YM, Gruffudd G, Hallamaa L, Haapaniemi T, Ihamuotila R, Juma J, Klein N, Luoma J, Martell O, Murugesan A, Okello C, Samake O, Traore CAT, Vehmasto T, Ylikruuvi K, Sow S, Ashorn P. Mass Administration of Azithromycin to Infants in Mali to Reduce Mortality. N Engl J Med. 2025 Oct 16;393(15):1498-1508. doi: 10.1056/NEJMoa2504644.
PubMed 41092331Luoma J, Adubra L, Alber D, Ashorn P, Ashorn U, Cloutman-Green E, Diallo F, Ducker C, Elovainio R, Fan YM, Gates L, Gruffudd G, Haapaniemi T, Haidara F, Hallamaa L, Ihamuotila R, Klein N, Martell O, Sow S, Vehmasto T, Cheung YB. 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. Trials. 2023 Nov 15;24(1):733. doi: 10.1186/s13063-023-07771-6.
PubMed 37968741Adubra L, Alber D, Ashorn P, Ashorn U, Cheung YB, Cloutman-Green E, Diallo F, Ducker C, Elovainio R, Fan YM, Gates L, Gruffudd G, Haapaniemi T, Haidara F, Hallamaa L, Ihamuotila R, Klein N, Luoma J, Martell O, Sow S, Vehmasto T; LAKANA Trial Team. 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 Jan 3;24(1):5. doi: 10.1186/s13063-022-06966-7.
PubMed 36597115
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT04424511
- Acronym / sponsor ID
- LAKANA / LAKANA trial
- Conditions
- Mortality
- Keywords
- Mass Drug Administration, Azithromycin, Infant and Child Mortality, Infant and Child health, Infant and Child growth, Infant and Child morbidity, Antimicrobial Resistance, Feasibility
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 149,201 participants (actual)
- Lead sponsor
- Tampere UniversityUniversity, hospital or other
- Collaborators
- Center for Vaccine Development CVD-Mali, Bamako, Mali, University College London Hospitals, Tro Da Ltd, UK, Duke-NUS Graduate Medical School, Bill and Melinda Gates Foundation, Pfizer Inc. (Provider of study drugs)
- Study start
- 15 Oct 2020 (actual)
- Primary completion
- 31 Dec 2024 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 11 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- LAKANA is a cluster-randomized, placebo-controlled, double-blinded, parallel-group, three-arm clinical trial, with adaptive design.
| Arm | Type | Receives |
|---|---|---|
| Control | Placebo comparator | Drug: PlaceboPlacebo 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. |
| Azithromycin-biannually (Azi-biannual) | Active comparator | Drug: Placebo, Drug: AzithromycinAzithromycin 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. |
| Azithromycin-quarterly | Active comparator | Drug: AzithromycinAzithromycin 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. |
Who may qualify
- Ages
- 29 to 364 days
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (12 listed)
- Location within Kayes, Kita, or Koulikoro region of Mali
- Considered accessible and safe by the local health authorities and research team
- Considered non-urban by the local health authorities and research team
- Permission from community leadership
- Location within a cluster that is included in the study
Key exclusion criteria (3 listed)
- Weight below 3.0 kg
- Known allergy to macrolides, as judged by a caregiver report of the infant experiencing an adverse reaction after oral ingestion of medication, which was deemed likely to be a macrolide by the interviewing data collector.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboPlacebo 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-biannually (Azi-biannual), Control |
| AzithromycinAzithromycin 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. | Drug | Azithromycin-biannually (Azi-biannual), Azithromycin-quarterly |
Primary outcome
Mortality
Time frame: 3-month time interval (total of 8 intervals per cluster)
Mortality rate (deaths per 1,000 years at risk) among children 1-11 months of age.
24 secondary outcomes
Morbidity
Time frame: 3-month time interval (total of 8 intervals per cluster)
Length-for-age Z-score
Time frame: 3-month time interval (total of 3 intervals per cluster)
Length
Time frame: 3-month time interval (total of 3 intervals per cluster)
Weight
Time frame: 3-month time interval (total of 3 intervals per cluster)
Weight-for age Z-score
Time frame: 3-month time interval (total of 3 intervals per cluster)
Weight-for-length Z-score
Time frame: 3-month time interval (total of 3 intervals per cluster)
Mid-upper arm circumference
Time frame: 3-month time interval (total of 3 intervals per cluster)
Percentage of moderate or severe stunting
Time frame: 3-month time interval (total of 3 intervals per cluster)
Percentage of moderate or severe wasting
Time frame: 3-month time interval (total of 3 intervals per cluster)
Percentage of moderate or severe Underweight
Time frame: 3-month time interval (total of 3 intervals per cluster)
Prevalence of phenotypic and genotypic macrolide resistance
Time frame: 12-month time interval (total of 3 intervals per cluster)
Prevalence of phenotypic and genotypic macrolide resistance
Time frame: 12-month time interval (total of 3 intervals per cluster)
Prevalence of phenotypic and genotypic macrolide resistance
Time frame: 12-month time interval (total of 3 intervals per cluster)
Prevalence of phenotypic and genotypic macrolide resistance
Time frame: 12-month time interval (total of 3 intervals per cluster)
Prevalence of phenotypic and genotypic AMR resistance to other "ACCESS" group antibiotics
Time frame: 12-month time interval (total of 3 intervals per cluster)
Blood C-reactive protein concentration
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
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
Time frame: Biological samples taken before and 14 days after the fourth MDA round, 9 months after village enrollment.
Incidence of Adverse events
Time frame: 3-month time interval
Incidence of Serious Adverse events
Time frame: within 14 days after MDA round.
Mortality in children aged 12-59 month
Time frame: 3-month time interval (total of 8 intervals per cluster)
Percentage of guardians and health care workers reporting MDA acceptable
Time frame: 24 months after enrollment
Percentage of the study population reached with MDA
Time frame: 24 months after enrollment
Cost and Cost-effectiveness of the intervention
Time frame: 24 months after enrollment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2025.
- Derived from this study: PubMed 42623398Ihamuotila R, Juma J, Haidara F, Samake O, Luoma J, Adubra L, Cheung YB, Alber D, Traore A, Ducker C, Ashorn U, Ashorn P, Sow S, Fan YM. A single dose of azithromycin versus placebo for malaria in infants: A cluster-randomized trial. PLOS Glob Public Health. 2026 Aug 20;6(8):e0006518. doi: 10.1371/journal.pgph.0006518. eCollection 2026.
- Derived from this study: PubMed 42268611Adubra L, Luoma J, Fan YM, Haidara FC, Samake O, Ihamuotila R, Ylikruuvi K, Hallamaa L, Martell O, Ducker C, Alber D, Ashorn P, Cheung YB, Sow S, Ashorn U. Infant Growth After Mass Administration of Azithromycin: Secondary Outcomes of a Cluster Randomized Clinical Trial. JAMA Netw Open. 2026 Jun 1;9(6):e2617425. doi: 10.1001/jamanetworkopen.2026.17425.
- Derived from this study: PubMed 41092331Haidara FC, Adubra L, Abdou M, Alber D, Ashorn U, Cheung YB, Cloutman-Green E, Diallo M, Ducker C, Fan YM, Gruffudd G, Hallamaa L, Haapaniemi T, Ihamuotila R, Juma J, Klein N, Luoma J, Martell O, Murugesan A, Okello C, Samake O, Traore CAT, Vehmasto T, Ylikruuvi K, Sow S, Ashorn P. Mass Administration of Azithromycin to Infants in Mali to Reduce Mortality. N Engl J Med. 2025 Oct 16;393(15):1498-1508. doi: 10.1056/NEJMoa2504644.
- Derived from this study: PubMed 37968741Luoma J, Adubra L, Alber D, Ashorn P, Ashorn U, Cloutman-Green E, Diallo F, Ducker C, Elovainio R, Fan YM, Gates L, Gruffudd G, Haapaniemi T, Haidara F, Hallamaa L, Ihamuotila R, Klein N, Martell O, Sow S, Vehmasto T, Cheung YB. 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. Trials. 2023 Nov 15;24(1):733. doi: 10.1186/s13063-023-07771-6.
- Derived from this study: PubMed 36597115Adubra L, Alber D, Ashorn P, Ashorn U, Cheung YB, Cloutman-Green E, Diallo F, Ducker C, Elovainio R, Fan YM, Gates L, Gruffudd G, Haapaniemi T, Haidara F, Hallamaa L, Ihamuotila R, Klein N, Luoma J, Martell O, Sow S, Vehmasto T; LAKANA Trial Team. 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 Jan 3;24(1):5. doi: 10.1186/s13063-022-06966-7.
- The study website providing access to essential study materials, including the study protocol, Statistical Analysis Plan (SAP), Standard Operating Procedures (SOPs), and Data Collection Forms (DCFs).Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual participant data collected during the trial, after deidentification. (The details are to be determined).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Per Ashorn, MD, PhD principal investigator
Center for Child Health Research, Tampere University
Ulla Ashorn, PhD principal investigator
Center for Child Health Research, Tampere University
Samba Sow, MD, MSc principal investigator
Center for Vaccine Development CVD-Mali
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Azithromycin in people with Mortality, run by Tampere University at 1 site in Mali.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mali. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality (time frame: 3-month time interval (total of 8 intervals per cluster)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04424511, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2025.