Infant Mortality Reduction by the Mass Administration of Azithromycin

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Child Mortality

Intervention / Treatment
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* Drug: Azithromycin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 11 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: The study will be a double-blind, placebo-controlled, cluster-randomized trial in which health centers (CSPS) in the 3 intervention regions will be randomized to either CHD combined with placebo (33%) or CHD combined with Azithromycin (67%), an allocation of 1:2 that favors active treatment. The allocation sequence and treatment labels will be masked to all but one biostatistician and one analyst at UCSF. The placebo will be indistinguishable from the active azithromycin. 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 to CHD+placebo or CHD+azithromycin
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Biannual mass oral azithromycin + child health days<br>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<br>* 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.<br>* Other names: Zithromax;|
| Placebo Comparator: Biannual mass placebo + child health days<br>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<br>* Matching identical placebo in packaging, appearance, and taste.<br>|
| Active Comparator: Resistance Sub Study: Azithromycin + Child Health Days<br>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<br>* 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.<br>* Other names: Zithromax;|
| Placebo Comparator: Resistance Sub Study: Placebo + Child Health Days<br>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<br>* Matching identical placebo in packaging, appearance, and taste.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Azithromycin, Mass Drug Administration, Child Mortality