Azithromycin for Child Survival in Niger: Programmatic Trial (AVENIR)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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 Design
Arms and Interventions
| 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:
|
| No Intervention: no intervention No additional intervention. |
Outcome Measures
Primary Outcome Measures
- Prevalence of genetic determinants of macrolide resistance from population-based samples [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 [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).
Secondary Outcome Measures
- Prevalence of genetic determinants of macrolide resistance from clinic-based samples [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 [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 [1 year]
Number of all-cause clinic visits per month for children aged 1-59 months over 1 year
Eligibility Criteria
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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- University of California, San Francisco
- Bill and Melinda Gates Foundation
- Ministry of Health, Niger
Investigators
- Principal Investigator: Kieran O'Brien, MPH, PhD, University of California, San Francisco
- Principal Investigator: Tom Lietman, MD, University of California, San Francisco
Study Documents (Full-Text)
None provided.More Information
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/
- 19-28387C