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

NCT05288023 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: 19-28387C
• Study Type: interventional
• Target: 169,707
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Resistance Bacterial; Morality; Child Health; Implementation

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Prevalence of Genetic Determinants of Macrolide Resistance From Clinic-based Samples

  2 years

• Load of Genetic Determinants of Macrolide Resistance From Clinic-based Samples

  2 years

• Number of All-cause Clinic Visits

  2 years

Study Arms (2)

Programmatic azithro 1-11

ACTIVE COMPARATOR

Biannual oral azithromycin administration to children aged 1-11 months distributed by community health workers

Drug: Azithromycin for Oral Suspension

no intervention

NO INTERVENTION

No additional intervention.

Interventions

Azithromycin for Oral Suspension DRUG

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.

Also known as: Zithromax

Programmatic azithro 1-11

Eligibility Criteria

• Age: 1 Month+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Location in Dosso, Tahoua, Maradi, Zinder, or Tillabéri regions
• Distinguishable from neighboring communities
• Verbal consent of community leader(s)

You may not qualify if:

• Inaccessible or unsafe for study team
• "Quartier" designation on national census
• At the individual-level, eligibility includes:
• Age 1-11 months
• Primary residence in a study community
• Verbal consent of caregiver/guardian for study participation
• Known allergy to macrolides
• Population-based sample collections
• At the community-level, eligibility includes:
• Location in study region
• Distinguishable from neighboring communities
• Verbal consent of community leader(s)
• Inaccessible or unsafe for study team
• Included in MORDOR trials
• Not randomly selected

Sponsors & Collaborators

• University of California, San Francisco: lead
• Bill and Melinda Gates Foundation: collaborator
• Ministry of Health, Niger: collaborator

Study Sites (1)

Proctor foundation

San Francisco, California, 94143, United States

Location

Related Publications (2)

• 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/

  PMID: 32924384 BACKGROUND

• 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.

  PMID: 29694816 BACKGROUND

MeSH Terms

Interventions

Azithromycin; Suspensions

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Kieran O'Brien
• Organization: University of California San Francisco

kieran.obrien@ucsf.edu

(415) 476-1442

Study Officials

• Kieran O'Brien, PhD, MPH

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Tom Lietman, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Participants, investigators, and program implementers will not be actively masked from the study arm allocation given that no placebo will be used. Outcome assessors and data analysts will be masked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Cluster-randomized trial with response adaptive allocation

Study Record Dates

• First Submitted: February 23, 2022
• First Posted: March 18, 2022
• Study Start: December 1, 2022
• Primary Completion: January 15, 2024
• Study Completion: January 15, 2024
• Last Updated: March 28, 2025
• Results First Posted: March 28, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Individual participant data will be made available after publication of the outcomes and will be made available indefinitely.
• Access Criteria: Once made available, the data will be open access.

Locations

US (1)