Clinical trial NCT06358872: Azithromycin for Child Survival in Niger II
Official title: Azithromycine Pour la Vie Des Enfants au Niger II
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Mortality
Antimicrobial Resistance
Keywords: Mass Treatment
Azithromycin
Childhood Mortality Rate
Antimicrobial Resistance
Implementation and Cost Analysis
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Centre de recherche et interventions en santé publique (CRISP)
name: Ministère de la Santé Publique du Niger
name: Le Programme National de Santé Oculaire
name: Centre de Recherche Médicale et Sanitaire
name: Bill and Melinda Gates Foundation
First posted: 2024-04-11
Enrollment: 3300000
Sex: ALL
Minimum age (years): 1
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The intervention will involve biannual oral azithromycin MDA to children 1-59 months old distributed by community health workers. The Centre de Santé Integré (CSI) will be randomized to receive azithromycin MDA or delayed treatment in a stepped wedge design for the first 2 years. The delayed intervention arm will receive usual care for the first 2 years, then will receive the intervention for the next 2 years.
Primary purpose: TREATMENT

Brief summary: Several randomized controlled trials have demonstrated that azithromycin mass drug administration (MDA) reduces child mortality, but increases antimicrobial resistance (AMR). The World Health Organization (WHO) guidelines for this intervention specify that implementation must be accompanied by continued monitoring of mortality and AMR. Niger is expanding the azithromycin MDA program nationwide. To establish monitoring of mortality and AMR as part of this program as well as to leverage the infrastructure to evaluate other child health interventions, AVENIR II is designed as an adaptive platform trial with monitoring and re-randomization every 2 years.

Detailed description: AVENIR II is a cluster-randomized adaptive platform trial designed to evaluate community health interventions in Niger. The initial focus is to monitor under-5 mortality and antimicrobial resistance as the azithromycin MDA for child survival program expands in Niger, with the following specific aims:

1. Mortality.

   1. To conduct surveillance of mortality over time compared to the Sustainable Development Goal targets for under-5 mortality reduction. As this intervention is not intended to continue indefinitely, surveillance against a target is needed to determine when to stop.
   2. To continue to evaluate the effectiveness of azithromycin MDA to reduce under-5 mortality. Given the risk of AMR, the effectiveness of the intervention over time is needed to fully weigh the risks against the benefits.
2. Antimicrobial Resistance. To determine the impact of azithromycin MDA on AMR in population- and clinic-based samples.

Eligibility criteria: Inclusion Criteria:

CSI-level for mortality and AMR monitoring:

* Located in a region participating in the program
* Designated as rural by local study team
* Selected for participation in monitoring activities
* Safe and accessible for study teams
* Verbal approval from community leaders

Individual level for mortality monitoring:

* Residing in the catchment area of an eligible CSI
* Selected for participation in monitoring activities
* Female
* Age between 12 and 55 years old
* Verbal approval from participant

Individual-level for AMR monitoring:

* Residing in the catchment area of an eligible CSI
* Selected for participation in monitoring activities
* Age between 1 and 59 months old
* Verbal approval from a caregiver or guardian

Exclusion Criteria:

At the community-level:

* Designated as urban by local study team
* Inaccessible or unsafe for study team

At the individual-level:

* Known allergy to macrolides

Primary outcomes:
measure: All-cause mortality
timeFrame: 2 years
measure: All-cause mortality
timeFrame: 4 years
measure: Prevalence of resistance to macrolides - nasopharyngeal swabs
timeFrame: 2 years
measure: Prevalence of resistance to macrolides - nasopharyngeal swabs
timeFrame: 4 years
measure: Load of genetic determinants of resistance to macrolides - rectal swabs
timeFrame: 2 years
measure: Load of genetic determinants of resistance to macrolides - rectal swabs
timeFrame: 4 years
Secondary outcomes:
measure: Number of clinic visits - infectious
timeFrame: 2 years
measure: Number of clinic visits - infectious
timeFrame: 4 years
measure: Prevalence of Genetic Determinants of resistance - Nasopharyngeal swabs
timeFrame: 2 years
measure: Prevalence of Genetic Determinants of resistance - Nasopharyngeal swabs
timeFrame: 4 years
measure: Program Cost Per Dose Delivered
timeFrame: 2 years
Other outcomes:
Locations:
city: Niamey
country: Niger
facility: Program National de Santé Oculaire
Study officials:
affiliation: University of California, San Francisco
name: Kieran S O'Brien, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Oldenburg CE, Ouattara M, Bountogo M, Boudo V, Ouedraogo T, Compaore G, Dah C, Zakane A, Coulibaly B, Bagagnan C, Hu H, O'Brien KS, Nyatigo F, Keenan JD, Doan T, Porco TC, Arnold BF, Lebas E, Sie A, Lietman TM. Mass Azithromycin Distribution to Prevent Child Mortality in Burkina Faso: The CHAT Randomized Clinical Trial. JAMA. 2024 Feb 13;331(6):482-490. doi: 10.1001/jama.2023.27393.
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citation: Keenan JD, Ayele B, Gebre T, Zerihun M, Zhou Z, House JI, Gaynor BD, Porco TC, Emerson PM, Lietman TM. Childhood mortality in a cohort treated with mass azithromycin for trachoma. Clin Infect Dis. 2011 Apr 1;52(7):883-8. doi: 10.1093/cid/cir069.
citation: O'Brien KS, Cotter SY, Amza A, Kadri B, Nassirou B, Stoller NE, Zhou Z, West SK, Bailey RL, Keenan JD, Porco TC, Lietman TM. Childhood Mortality After Mass Distribution of Azithromycin: A Secondary Analysis of the PRET Cluster-randomized Trial in Niger. Pediatr Infect Dis J. 2018 Nov;37(11):1082-1086. doi: 10.1097/INF.0000000000001992.
citation: 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.
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citation: Keenan JD, Arzika AM, Maliki R, Elh Adamou S, Ibrahim F, Kiemago M, Galo NF, Lebas E, Cook C, Vanderschelden B, Bailey RL, West SK, Porco TC, Lietman TM; MORDOR-Niger Study Group. Cause-specific mortality of children younger than 5 years in communities receiving biannual mass azithromycin treatment in Niger: verbal autopsy results from a cluster-randomised controlled trial. Lancet Glob Health. 2020 Feb;8(2):e288-e295. doi: 10.1016/S2214-109X(19)30540-6.
citation: 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/
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