Azithromycin for Child Survival in Niger: Mortality and Resistance Trial (AVENIR)

July 14, 2026 updated by: University of California, San Francisco

Azithromycine Pour la Vie Des Enfants au Niger - Implémentation et Recherche: Essai mortalité et résistance (Azithromycin for Child Survival in Niger: Mortality Trial and Resistance Trial)

The MORDOR trial found that biannual distribution of azithromycin to children 1-59 months old reduced child mortality. The World Health Organization (WHO) released conditional guidelines for this intervention, which include targeting azithromycin distributions to children 1-11 months of age in high mortality settings.Targeting treatment to children 1-11 months old could reduce antimicrobial resistance by limiting antibiotic distributions while treating children at the highest mortality risk. However, this targeted intervention has not yet been tested.

The AVENIR mortality/resistance trial aims to assess the efficacy of age-based targeting of biannual azithromycin distribution on mortality as well as determine the impact of age-based targeting on antimicrobial resistance.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In the Mortality/Resistance trial, 3,000 communities in the Dosso and Tahoua regions of Niger will be randomized to one of three arms: 1) azithro 1-11: biannual oral azithromycin to children 1-11 months old with biannual oral placebo to children 12-59 months old, 2) azithro 1-59: biannual oral azithromycin to children 1-59 months old, or 3) placebo: biannual oral placebo to children 1-59 months old. Interventions will be delivered biannually through a door-to-door census. Mortality will also be monitored through biannual census data collection, which will be used to adaptively allocate treatment assignments after the first year. Communities will retain an allocation for 4 distributions before being re-randomized.

Antimicrobial resistance will be monitored using cluster sampling of treated and untreated children and adults in the Dosso region.

To compare costs, coverage, and acceptability of treating 1-11-month-old children only vs children 1-59 months old, an additional 80 communities in the Dosso region will be selected. These communities will be randomized in a 1:1 fashion to either receive 1) distribution of open-label azithromycin to children 1-11 months old with no intervention to children 12-59 months old or 2) distribution of open-label azithromycin to children 1-59 months old. The primary outcome for this substudy will be community-level costs per dose delivered. Secondary outcomes include program costs, treatment coverage, and acceptability of the intervention according to community leaders, community health workers, and caregivers of eligible children.

Study Type

Interventional

Enrollment (Actual)

864493

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Niger
      • Niamey, Niger
        • Programme national de santé oculaire

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 4 years (Child)

Accepts Healthy Volunteers

Yes

Description

  1. Intervention

    At the community-level, eligibility includes:

    Inclusion Criteria:

    • Location in Dosso, Tahoua, Maradi, Zinder, or Tillabéri regions
    • Population 250 to 2,499*
    • Distance > 5 km from district headquarters town
    • Distinguishable from neighboring communities
    • Verbal consent of community leader(s)

    Exclusion criteria:

    • Inaccessible or unsafe for study team
    • "Quartier" designation on national census *Population size as estimated from the most recent national census or projections

    At the individual-level, eligibility includes:

    Inclusion criteria:

    • Age 1-59 months
    • Primary residence in a study community
    • Verbal consent of caregiver/guardian for study participation
    • Weight ≥ 3.0 kg (*no weight limits in communities using age-based dosing)

    Exclusion criteria:

    • Known allergy to macrolides

  2. Population-based sample collections

At the community-level, eligibility includes:

Inclusion Criteria:

  • Location in Dosso
  • Distinguishable from neighboring communities
  • Verbal consent of community leader(s)

Exclusion criteria:

  • Inaccessible or unsafe for the study team
  • Included in MORDOR trials
  • Not randomly selected
  • Received treatment prior to sample collection

At the individual-level, eligibility includes:

Inclusion Criteria:

  • Age 1-59 months or 7-12 years or caregiver/guardian of a child eligible for treatment
  • Primary residence in a study community selected for sample collections
  • Verbal consent of caregiver/guardian for study participation

Exclusion criteria:

• An individual is not on the list of randomly selected participants from the census

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Azithro 1-11
Biannual weight- or height-based dose of oral azithromycin suspension to children 1-11 months old and oral placebo or no intervention to children 12-59 months old
Drug: Azithromycin

Azithromycin will be administered as a directly observed dose in oral suspension form for children:

  1. Single-dose of 20mg/kg in children (up to the maximum adult dose of 1g)
  2. For children 1-11 months of age, weight or age-based dosing will be used
  3. For children 12-59 months of age, height-based dosing will be used via height-stick approximation as currently performed by Niger's trachoma program
Other Names:
  • Zithromax
Other: Placebo

Placebo will be administered as a directly observed dose in oral suspension form for children:

  1. Single-dose of 20mg/kg in children (up to the maximum adult dose of 1g)
  2. For children 1-11 months of age, weight-based dosing will be used
  3. For children 12-59 months of age, height-based dosing will be used via height-stick approximation as currently performed by Niger's trachoma program
Active Comparator: Azithro 1-59
Biannual age, weight- or height-based dose of oral azithromycin suspension to children 1-59 months old
Drug: Azithromycin

Azithromycin will be administered as a directly observed dose in oral suspension form for children:

  1. Single-dose of 20mg/kg in children (up to the maximum adult dose of 1g)
  2. For children 1-11 months of age, weight or age-based dosing will be used
  3. For children 12-59 months of age, height-based dosing will be used via height-stick approximation as currently performed by Niger's trachoma program
Other Names:
  • Zithromax
Placebo Comparator: Placebo
Biannual weight- or height-based dose of oral placebo to children 1-59 months old
Other: Placebo

Placebo will be administered as a directly observed dose in oral suspension form for children:

  1. Single-dose of 20mg/kg in children (up to the maximum adult dose of 1g)
  2. For children 1-11 months of age, weight-based dosing will be used
  3. For children 12-59 months of age, height-based dosing will be used via height-stick approximation as currently performed by Niger's trachoma program

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All-cause Mortality (1-59 Months Old)
Time Frame: from 6 months up to 2.5 years
Mortality rate (deaths per 1,000 person-years at risk) among children 1-59 months of age, comparing the azithro 1-59 and placebo arms.
from 6 months up to 2.5 years
All-cause Mortality (1-11 Months Old)
Time Frame: from 6 months up to 2.5 years
Mortality rate (deaths per 1,000 person-years at risk) among children 1-11 months of age, comparing the azithro 1-11 and placebo arms.
from 6 months up to 2.5 years
All-cause Mortality (12-59 Months Old)
Time Frame: from 6 months up to 2.5 years
Mortality rate (deaths per 1,000 person-years at risk) among children 12-59 months of age with rates compared between azithro 1-11 and azithro 1-59 communities.
from 6 months up to 2.5 years
Prevalence of Resistance to Macrolides - Nasopharyngeal Swabs (1-59 Months Old)
Time Frame: After 4 distributions (approximately 24 months)
Prevalence of macrolide resistance among pneumococcus-positive nasopharyngeal swabs collected from children aged 1-59 months after 4 distributions. Resistance was assessed among culture-positive pneumococcal isolates from nasopharyngeal swabs.
After 4 distributions (approximately 24 months)
Load of Genetic Determinants of Resistance to Macrolides - Rectal Swabs (1-59 Months Old)
Time Frame: After 4 distributions (approximately 24 months)
Community-level load of macrolide antimicrobial resistance determinants in pooled rectal swabs collected from children aged 1-59 months after four biannual distributions. Rectal swabs from each community were pooled and analyzed using metagenomic DNA sequencing. Nonhost sequencing reads were aligned to an antimicrobial resistance reference database, and reads matching macrolide resistance determinants were summed and normalized to the total number of nonhost reads in the pooled sample. Values are reported as matched resistance reads per million nonhost reads (rM). Higher values indicate a greater abundance of macrolide resistance determinants. The values presented in the table are untransformed normalized counts.
After 4 distributions (approximately 24 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality Rate by Weight-for-age Z-score Subgroup Among Infants Aged 1-11 Months
Time Frame: After 4 distributions (approximatively 24 month after first distribution)
All-cause mortality incidence rate among children aged 1-11 months who had weight measured during at least one census round and had a valid weight-for-age z-score calculated using the World Health Organization Child Growth Standards. Nutritional status was assessed at the beginning of each census interval. This measure reports the overall mortality rate for this analysis population by randomized treatment arm and is not stratified by weight-for-age z-score subgroup. Mortality rates are reported as deaths per 1,000 person-years.
After 4 distributions (approximatively 24 month after first distribution)
Load of Genetic Determinants of Resistance to Macrolides in Nasopharyngeal Swabs From Guardians
Time Frame: After 4 distributions (approximatively 24 month after first distribution)
Community-level loads of macrolide antimicrobial resistance determinants in nasopharyngeal swabs collected from guardians of children eligible for treatment after four biannual distributions. Nasopharyngeal swabs from each community were pooled and analyzed using DNA sequencing. Nonhost sequencing reads were aligned to an antimicrobial resistance reference database, and reads matching macrolide resistance determinants were summed and normalized to the total number of nonhost reads in the pooled sample. Values are reported as matched resistance reads per million nonhost reads (rM). Higher values indicate a greater abundance of macrolide resistance determinants. The values presented in the table are untransformed normalized counts; log-transformed values were used only for inferential statistical analyses.
After 4 distributions (approximatively 24 month after first distribution)
Program Costs Per Dose Delivered
Time Frame: 1 year
Program cost per dose delivered was estimated using routine administrative data and micro-costing activities. Costs were calculated per dose delivered and were not stratified by randomized treatment arm.
1 year
Load of Genetic Determinants of Resistance to Macrolides in Nasopharyngeal Swabs From Children Aged 7-12 Years
Time Frame: After 4 distributions, approximately 24 months
Community-level loads of macrolide antimicrobial resistance determinants in nasopharyngeal swabs collected from children aged 7-12 years after four biannual distributions. Nasopharyngeal swabs from each community were pooled and analyzed using DNA sequencing. Nonhost sequencing reads were aligned to an antimicrobial resistance reference database, and reads matching macrolide resistance determinants were summed and normalized to the total number of nonhost reads in the pooled sample. Values are reported as matched resistance reads per million nonhost reads (rM). Higher values indicate a greater abundance of macrolide resistance determinants. The values presented in the table are untransformed normalized counts; log-transformed values were used only for inferential statistical analyses.
After 4 distributions, approximately 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

Bill and Melinda Gates Foundation
Ministry of Health, Niger

Investigators

  • Principal Investigator: Tom M Lietman, MD, University of California, San Francisco
  • Principal Investigator: Kieran S O'Brien, PhD, MPH, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 24, 2020

Primary Completion (Actual)

July 31, 2024

Study Completion (Actual)

July 31, 2024

Study Registration Dates

First Submitted

December 17, 2019

First Submitted That Met QC Criteria

January 8, 2020

First Posted (Actual)

January 13, 2020

Study Record Updates

Last Update Posted (Actual)

August 6, 2026

Last Update Submitted That Met QC Criteria

July 14, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 19-28387A

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified data underlying outcomes publications will be made publicly available.

IPD Sharing Time Frame

Individual participant data will be made available after publication of the outcomes and will be made available indefinitely.

IPD Sharing Access Criteria

Once made available, the data will be open access.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe