Azithromycin for Child Survival in Niger: Programmatic Trial (AVENIR)

Study Overview
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Brief Summary
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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. The proposed trial aims to demonstrate and evaluate large-scale implementation of azithromycin to children aged 1-11 months old in the context of a programmatic setting while monitoring mortality and resistance antimicrobial resistance.

Detailed Description
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In the Programmatic Trial, community health centers (also known as CSIs or Centres de Santé Intégrés) will be randomized to one of two arms: 1) programmatic azithro 1-11: biannual oral azithromycin administration to children aged 1-11 months distributed by community health workers or 2) no intervention: no distribution of azithromycin. A total of 2,490 communities within selected CSIs will be included . All communities in both arms receive routine health services offered by community health workers working for the Niger Ministry of Health's community health program. Mortality will be monitored through birth histories. Mortality and morbidity will also be monitored using routinely collected community and clinic visit data. Antimicrobial resistance will be monitored in a subset of eligible CSIs.

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

Conditions
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Resistance Bacterial, Morality, Child Health, Implementation

Intervention / Treatment
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* Drug: Azithromycin for Oral Suspension


Participation Criteria
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Eligibility Criteria
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Intervention At the community-level, eligibility includes: Inclusion Criteria: Location in Dosso, Tahoua, Maradi, Zinder, or Tillabéri regions Distinguishable from neighboring communities Verbal consent of community leader(s) Exclusion criteria: Inaccessible or unsafe for study team Quartier designation on national census At the individual-level, eligibility includes: Inclusion criteria: Age 1-11 months Primary residence in a study community Verbal consent of caregiver/guardian for study participation Exclusion criteria: Known allergy to macrolides Population-based sample collections At the community-level, eligibility includes: Inclusion criteria: Location in study region Distinguishable from neighboring communities Verbal consent of community leader(s) Exclusion criteria: Inaccessible or unsafe for study team Included in MORDOR trials Not randomly selected 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: Not on list of randomly selected participants from the census

Ages Eligible for Study
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Minimum Age: 1 Month

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Cluster-randomized trial with response adaptive allocation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Programmatic azithro 1-11<br>Biannual oral azithromycin administration to children aged 1-11 months distributed by community health workers | Drug: Azithromycin for Oral Suspension<br>* Azithromycin will be administered as a single dose in oral suspension form for children (up to the maximum adult dose of 1g). Dosage will be calculated by age for children aged 1-5 months. For children 6-59 months of age, height-based dosing will be used via height-stick approximation as currently performed by Niger's trachoma program.<br>* Other names: Zithromax;|
| No Intervention: no intervention<br>No additional intervention. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of genetic determinants of macrolide resistance from population-based samples | Prevalence of genetic determinants of macrolide resistance including those determinants known to be found in Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus in nasopharyngeal swabs in children aged 1-59 months from population-based samples after 1 year of distribution | 2 years | 
| Load of genetic determinants of macrolide resistance from population-based samples | Load of genetic determinants of resistance to macrolides including those determinants known to be found in Campylobacter spp, Salmonella spp, Shigella spp, and Escherichia coli from rectal swabs in children 1-59 months old from population-based samples, defined as read number per million base pairs, using DNA-seq (metagenomic deep sequencing). | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of genetic determinants of macrolide resistance from clinic-based samples | Prevalence of resistance to macrolides including those determinants known to be found in Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus from nasopharyngeal swabs in children 1-59 months old. | 2 years | 
| Load of genetic determinants of macrolide resistance from clinic-based samples | Load of genetic determinants of resistance to macrolides including those determinants known to be found in Campylobacter spp, Salmonella spp, Shigella spp, and Escherichia coli from rectal swabs in children 1-59 months old, defined as read number per million base pairs, using DNA-seq (metagenomic deep sequencing). | 2 years | 
| Number of all-cause clinic visits | Number of all-cause clinic visits per month for children aged 1-59 months over 1 year | 2 years |