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

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

Study Overview

• Status: Recruiting
• Conditions: Child Health; Morality; Implementation; Resistance Bacterial
• Intervention / Treatment: Drug: Azithromycin for Oral Suspension

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 250000
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Elodie Lebas; Phone Number: 5104232245; Email: elodie.lebas@ucsf.edu
• Study Contact Backup: Name: Sandrine Kyane; Email: sandrine.kyane@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • Proctor foundation
      • Contact: Elodie lebas, rn; Phone Number: 510-423-2245; Email: elodie.lebas@ucsf.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Programmatic azithro 1-11; Biannual oral azithromycin administration to children aged 1-11 months distributed by community health workers	Drug: Azithromycin for Oral Suspension; 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.; Other Names: Zithromax
No Intervention: no intervention; No additional intervention.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Bill and Melinda Gates Foundation; Ministry of Health, Niger
• Investigators: Principal Investigator: Kieran O'Brien, PhD, MPH, University of California, San Francisco; Principal Investigator: Tom Lietman, MD, University of California, San Francisco

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.
• WHO Guideline on Mass Drug Administration of Azithromycin to Children under Five Years of Age to Promote Child Survival [Internet]. Geneva: World Health Organization; 2020. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK561641/

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: February 23, 2022
• First Submitted That Met QC Criteria: March 15, 2022
• First Posted (Actual): March 18, 2022

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: 19-28387C

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