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

• ClinicalTrials.gov Identifier: NCT05288023
• Recruitment Status: Not yet recruiting
• First Posted: March 18, 2022
• Last Update Posted: September 7, 2022
• Sponsor: University of California, San Francisco
• Collaborators: Bill and Melinda Gates Foundation; Ministry of Health, Niger
• Information provided by (Responsible Party): University of California, San Francisco

Tracking Information

• First Submitted Date: February 23, 2022
• First Posted Date: March 18, 2022
• Last Update Posted Date: September 7, 2022
• Estimated Study Start Date: December 1, 2022
• Estimated Primary Completion Date: March 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 29, 2022)

• Prevalence of genetic determinants of macrolide resistance from population-based samples [ Time Frame: 1 year ]
  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
• Load of genetic determinants of macrolide resistance from population-based samples [ Time Frame: 1 year ]
  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).

Original Primary Outcome Measures (submitted: March 15, 2022)

• Infant mortality rate [ Time Frame: 2 years ]
  Infant mortality rate (deaths per 1,000 live births)
• Number of total and cause-specific clinic visits [ Time Frame: 1 year from the first distribution of azithromycin ]
  Number of total and cause-specific clinic visits for diarrhea, respiratory infection, and malaria among children aged 1-59 months visiting local health center clinics
• Prevalence of genetic determinants of macrolide resistance [ Time Frame: 1 year ]
  Prevalence of genetic determinants for macrolide resistance in nasopharyngeal swabs in children aged 1-59 months
• Load of genetic determinants of macrolide resistance [ Time Frame: 1 year ]
  Load of genetic determinants of macrolide resistance in rectal swabs among children aged 1-59 months

Current Secondary Outcome Measures (submitted: June 29, 2022)

• Prevalence of genetic determinants of macrolide resistance from clinic-based samples [ Time Frame: 1 year ]
  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.
• Load of genetic determinants of macrolide resistance from clinic-based samples [ Time Frame: 1 year ]
  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).
• Number of all-cause clinic visits [ Time Frame: 1 year ]
  Number of all-cause clinic visits per month for children aged 1-59 months over 1 year

Original Secondary Outcome Measures (submitted: March 15, 2022)

Program costs [ Time Frame: 1 year ]

Program costs as captured by routine administrative data collection during the study period and by micro-costing activities

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Cluster-randomized trial with response adaptive allocation

Masking: None (Open Label)
Masking Description:

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.

Primary Purpose: Treatment

Condition

• Resistance Bacterial
• Morality
• Child Health
• Implementation

Intervention

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 Name: Zithromax

Study Arms

• Active Comparator: Programmatic azithro 1-11
  Biannual oral azithromycin administration to children aged 1-11 months distributed by community health workers
  Intervention: Drug: Azithromycin for Oral Suspension
• No Intervention: no intervention
  No additional intervention.

Publications *

• 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/
• 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.

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: March 15, 2022): 250000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2026
• Estimated Primary Completion Date: March 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Month and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Elodie Lebas; 5104232245; elodie.lebas@ucsf.edu

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT05288023
• Other Study ID Numbers: 19-28387C
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: De-identified data underlying outcomes publications will be made publicly available.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (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.

• Current Responsible Party: University of California, San Francisco
• Original Responsible Party: Same as current
• Current Study Sponsor: University of California, San Francisco
• Original Study Sponsor: Same as current

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

• PRS Account: University of California, San Francisco
• Verification Date: September 2022