Effects of Mass Drug Administration of Azithromycin on Mortality and Other Outcomes Among 1-11 Month Old Infants in Mali

NCT04424511 | Completed Phase 3 DMC

• 2 other identifiers: LAKANA trialINV-003354
• Study Type: interventional
• Target: 149,201
• Locations: 1 country
• Sites: 1

Brief 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 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.

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; Acceptability; Safety; Cost; Inflammation; Infection

Outcome Measures

Primary Outcomes (1)

• Mortality

  Mortality rate (deaths per 1,000 years at risk) among children 1-11 months of age.

  3-month time interval (total of 8 intervals per cluster)

Secondary Outcomes (24)

• Morbidity

  3-month time interval (total of 8 intervals per cluster)

• Length-for-age Z-score

  3-month time interval (total of 3 intervals per cluster)

• Length

  3-month time interval (total of 3 intervals per cluster)

• Weight

  3-month time interval (total of 3 intervals per cluster)

• Weight-for age Z-score

  3-month time interval (total of 3 intervals per cluster)

Study Arms (3)

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.

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.

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.

Drug: Azithromycin

Interventions

Placebo DRUG

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-biannually (Azi-biannual); Control

Azithromycin DRUG

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.

Azithromycin-biannually (Azi-biannual); Azithromycin-quarterly

Eligibility Criteria

• Age: 29 Days - 364 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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):
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tampere University: lead
• Center for Vaccine Development CVD-Mali, Bamako, Mali: collaborator
• University College London Hospitals: collaborator
• Tro Da Ltd, UK: collaborator
• Duke-NUS Graduate Medical School: collaborator
• Bill and Melinda Gates Foundation: collaborator
• Pfizer Inc. (Provider of study drugs): collaborator

Study Sites (1)

Center for Vaccine Development CVD-Mali

Bamako, BP 251, Mali

Location

Related Publications (3)

• Haidara 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.

  PMID: 41092331 DERIVED

• Luoma 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.

  PMID: 37968741 DERIVED

• Adubra 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.

  PMID: 36597115 DERIVED

Related Links

• 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).

MeSH Terms

Conditions

Inflammation; Infections

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Per Ashorn, MD, PhD

  Center for Child Health Research, Tampere University

  PRINCIPAL INVESTIGATOR

• Ulla Ashorn, PhD

  Center for Child Health Research, Tampere University

  PRINCIPAL INVESTIGATOR

• Samba Sow, MD, MSc

  Center for Vaccine Development CVD-Mali

  PRINCIPAL INVESTIGATOR

• Nigel Klein, MBBS, PhD

  University College London Hospitals

  PRINCIPAL INVESTIGATOR

• Camilla Ducker, MBBS, MSc

  Tro Da Ltd, UK

  PRINCIPAL INVESTIGATOR

• Yin Bun Cheung, PhD

  Centre for Quantitative Medicine, Duke-NUS Medical School

  PRINCIPAL INVESTIGATOR

• Dagmar Alber, PhD

  University College London Hospitals

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The investigators will utilize a matching placebo to mask study arm allocation. All children aged 1-11 months in all study communities will be offered biannual or quarterly azithromycin or placebo distribution in an identical fashion. Placebo will be identical to azithromycin in appearance, taste, odor, and packaging. The interventions will be coded only with a letter code.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Professor of Pediatrics

Model Details: LAKANA is a cluster-randomized, placebo-controlled, double-blinded, parallel-group, three-arm clinical trial, with adaptive design.

Study Record Dates

• First Submitted: May 22, 2020
• First Posted: June 11, 2020
• Study Start: October 15, 2020
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: May 21, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Starting 6 months after publication
• Access Criteria: (The details are to be determined)

Locations

MA (1)