Infant Mortality Reduction by the Mass Administration of Azithromycin (MIRAMA)

Mortalite Infantile Reduite Par l'Administration de Masse de l'Azitromycine

This trial will investigate the supplementation of azithromycin distribution to the "Child Health Days" platform in Burkina Faso for child mortality reduction. This distribution will pair door-to-door administration of vitamin A and azithromycin or placebo with acute malnutrition screening among children 1-11 months old.

Study Overview

• Status: Active, not recruiting
• Conditions: Child Mortality
• Intervention / Treatment: Drug: Azithromycin; Drug: Placebo

Detailed Description

The MORDOR clinical trial funded by the Bill & Melinda Gates Foundation in Malawi, Tanzania, and Niger demonstrated that biannual oral azithromycin distributions to children aged 1-59 months significantly reduced child mortality. The investigators hypothesize that biannual administration of azithromycin to children aged 1-11 months will reduce mortality in this age group. The aim of the project is to demonstrate that this intervention can be scaled up and produce the same benefits on mortality as those documented in smaller, more controlled studies. Since 1986, to reduce child mortality, Burkina Faso has been administering high-dose vitamin A supplementation to children aged 6-59 months on a biannual basis through the "Child Health Days" platform. The "Child Health days" are a door-to-door distribution of vitamin A coupled with screening for acute malnutrition in children aged 6-59 months and deworming of children aged 12-59 months. This approach has been successful but expensive. A new strategy implemented since September 2017 relies on community-based health workers (CBHWs) to distribute Vitamin A in rural areas, and on community-based distributors (CDs) in urban areas. Based on expert opinion and the preliminary findings of formative research conducted by the Ministry of Health and Helen Keller International, it was agreed that the Child Health Days platform was the most appropriate platform to implement the biannual administration of azithromycin to children aged 1 to 11 months.

In this trial, mortality will be measured via complete birth history which will be collected in a subset of villages in the study area before the first treatment distribution. The study team will also conduct a baseline census of the study areas for treatment coverage estimations.

Sixty villages (30 azithromycin, 30 placebo) will contribute to the macrolide resistance outcomes, where the study team will collect rectal and nasal swabs from children 1-59 months.

• Study Type: Interventional
• Enrollment (Estimated): 694400
• Phase: Phase 4

Contacts and Locations

Study Locations

• Burkina Faso
  • Nouna, Burkina Faso
    • Centre de Recherche en Sante de Nouna
  • Ouagadougou, Burkina Faso
    • Helen Keller International
• United States
  • California
    • San Francisco, California, United States, 94158
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 11 months (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Community eligibility criteria:

• Located in one of the three selected regions: SudOuest, Centre-Ouest, Hauts-Bassins
• Verbal consent of the community leader is obtained

Inclusion criteria for children:

• Aged 1 to 11 months
• Living in one of the communities participating in the study

Exclusion Criteria:

Community exclusion criteria:

• Inaccessible or unsafe for the study team

Exclusion criteria for children:

• Known allergy to macrolides

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Biannual mass oral azithromycin + child health days; Bi-annual Mass Azithromycin distribution to all children 1-11 months old in participating communities paired with the Child Health Days Vitamin A distribution platform	Drug: Azithromycin; Azithromycin is a macrolide-type antibiotic that is used to treat various types of infections. Previous studies in Niger have demonstrated a nearly 18% reduction in all-cause child mortality following biannual mass administration to children 1-59 months.; Other Names: Zithromax
Placebo Comparator: Biannual mass placebo + child health days; Bi-annual Mass placebo distribution to all children 1-11 months old in participating communities paired with the Child Health Days Vitamin A distribution platform	Drug: Placebo; Matching identical placebo in packaging, appearance, and taste.
Active Comparator: Resistance Sub Study: Azithromycin + Child Health Days; Antimicrobial resistance will be monitored in a parallel study of communities from the target study area. 60 communities will be randomly selected among eligible communities, and randomized in a 1 : 1 fashion	Drug: Azithromycin; Azithromycin is a macrolide-type antibiotic that is used to treat various types of infections. Previous studies in Niger have demonstrated a nearly 18% reduction in all-cause child mortality following biannual mass administration to children 1-59 months.; Other Names: Zithromax
Placebo Comparator: Resistance Sub Study: Placebo + Child Health Days; Antimicrobial resistance will be monitored in a parallel study of communities from the target study area. 60 communities will be randomly selected among eligible communities, and randomized in a 1 : 1 fashion	Drug: Placebo; Matching identical placebo in packaging, appearance, and taste.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	a) Evaluate whether azithromycin integrated within the VAD+ platform reduces mortality in children aged 1-11 months old compared to placebo	24 months following baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antimicrobial Resistance (AMR)	b) To compare the cluster level load of genetic determinants of macrolides resistance in rectal samples collected from children 1-59 months old in the clusters receiving azithromycin compared to the clusters receiving placebo	24 months
Clinic Visits	b) Evaluate whether azithromycin integrated within the VAD+ platform changes the rate of clinic visits in children aged 1-11 month old compared to placebo.	24 months

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Bill and Melinda Gates Foundation; Helen Keller International; Centre de Recherche en Sante de Nouna, Burkina Faso
• Investigators: Principal Investigator: Thomas Lietman, MD, University of California, San Francisco; Study Director: Georges Dimithe, Helen Keller International

Publications and helpful links

General Publications

• Keenan JD, Bailey RL, West SK, Arzika AM, Hart J, Weaver J, Kalua K, Mrango Z, Ray KJ, Cook C, Lebas E, O'Brien KS, Emerson PM, Porco TC, Lietman TM; MORDOR Study Group. Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa. N Engl J Med. 2018 Apr 26;378(17):1583-1592. doi: 10.1056/NEJMoa1715474.

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2021
• Primary Completion (Actual): January 30, 2025
• Study Completion (Estimated): January 30, 2026

Study Registration Dates

• First Submitted: January 15, 2021
• First Submitted That Met QC Criteria: January 15, 2021
• First Posted (Actual): January 20, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 12, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Azithromycin; Mass Drug Administration; Child Mortality
• Additional Relevant MeSH Terms: Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin
• Other Study ID Numbers: 20-32979

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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