Azithromycin for Child Survival in Niger II

NCT06358872 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 23-39839
• Study Type: interventional
• Target: 3,300,000
• Locations: 1 country
• Sites: 1

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.

Conditions

Mortality; Antimicrobial Resistance

Keywords

Mass Treatment; Azithromycin; Childhood Mortality Rate; Antimicrobial Resistance; Implementation and Cost Analysis

Outcome Measures

Primary Outcomes (6)

• All-cause mortality

  Under-5 mortality rate (U5MR, deaths per 1,000 live births) assessed by pregnancy history at 2 years from the first treatment distribution, comparing the intervention and delayed arms

  2 years

• All-cause mortality

  Under-5 mortality rate (U5MR, deaths per 1,000 live births) assessed by pregnancy history at 4 years, comparing the continue and stop arms

  4 years

• Prevalence of resistance to macrolides - nasopharyngeal swabs

  Prevalence of macrolide-resistant pneumococcus from nasopharyngeal swabs in children 1-59 months old after 2 years of distributions, comparing the intervention and delayed arms

  2 years

• Prevalence of resistance to macrolides - nasopharyngeal swabs

  Prevalence of macrolide-resistant pneumococcus from nasopharyngeal swabs in children 1-59 months old after 4 years of distributions, comparing the continue and stop arms

  4 years

• Load of genetic determinants of resistance to macrolides - rectal swabs

  Load of genetic determinants of resistance to macrolides from rectal swabs in children 1-59 months old after 2 years of distributions, comparing the intervention and delayed arms

  2 years

• Load of genetic determinants of resistance to macrolides - rectal swabs

  Load of genetic determinants of resistance to macrolides from rectal swabs in children 1-59 months old after 4 years of distributions, comparing the continue and stop arms

  4 years

Secondary Outcomes (5)

• Number of clinic visits - infectious

  2 years

• Number of clinic visits - infectious

  4 years

• Prevalence of Genetic Determinants of resistance - Nasopharyngeal swabs

  2 years

• Prevalence of Genetic Determinants of resistance - Nasopharyngeal swabs

  4 years

• Program Cost Per Dose Delivered

  2 years

Study Arms (3)

Continuous Distribution

ACTIVE COMPARATOR

Azithromycin distribution to children 1-59 months of age for four years using a door-to-door delivery approach via existing community health workers

Drug: Azithromycin for Oral Suspension

Delayed Distribution

ACTIVE COMPARATOR

Delayed, by two years, azithromycin distribution to children 1-59 months of age using a door-to-door delivery approach via existing community health workers

Drug: Azithromycin for Oral Suspension

Stop Distribution

ACTIVE COMPARATOR

Stopping azithromycin distribution after two years to children 1-59 months of age using a door-to-door delivery approach via existing community health workers

Drug: Azithromycin for Oral Suspension

Interventions

Azithromycin for Oral Suspension DRUG

Azithromycin will be administered as a single dose, in oral suspension form for children. The dose will be calculated by age or height depending on the child's age Both dosing cups and syringes will be used to administer treatment. For children too young to drink out of a dosing cup, a 1 ml or 5 ml syringe will be used, and the calculated dose will be rounded upwards to the nearest 0.2 ml.

Also known as: Zithromax

Continuous Distribution; Delayed Distribution; Stop Distribution

Eligibility Criteria

• Age: 1 Month - 59 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• Centre de recherche et interventions en santé publique (CRISP): collaborator
• Ministère de la Santé Publique du Niger: collaborator
• Le Programme National de Santé Oculaire: collaborator
• Centre de Recherche Médicale et Sanitaire: collaborator
• Bill and Melinda Gates Foundation: collaborator

Study Sites (1)

Program National de Santé Oculaire

Niamey, Niger

RECRUITING

Related Publications (11)

• 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.

  PMID: 38349371 BACKGROUND

• Sie A, Ouattara M, Bountogo M, Boudo V, Ouedraogo T, Compaore G, Dah C, Bagagnan C, Lebas E, Hu H, Rice J, Porco TC, Arnold BF, Lietman TM, Oldenburg CE. Azithromycin during Routine Well-Infant Visits to Prevent Death. N Engl J Med. 2024 Jan 18;390(3):221-229. doi: 10.1056/NEJMoa2309495.

  PMID: 38231623 BACKGROUND

• Chao DL, Arzika AM, Abdou A, Maliki R, Karamba A, Galo N, Beidi D, Harouna N, Abarchi M, Root E, Mishra A, Lebas E, Arnold BF, Oldenburg CE, Keenan JD, Lietman TM, O'Brien KS. Distance to Health Centers and Effectiveness of Azithromycin Mass Administration for Children in Niger: A Secondary Analysis of the MORDOR Cluster Randomized Trial. JAMA Netw Open. 2023 Dec 1;6(12):e2346840. doi: 10.1001/jamanetworkopen.2023.46840.

  PMID: 38100110 BACKGROUND

• 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.

  PMID: 21427395 BACKGROUND

• 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.

  PMID: 29561511 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

• Doan T, Hinterwirth A, Worden L, Arzika AM, Maliki R, Abdou A, Kane S, Zhong L, Cummings ME, Sakar S, Chen C, Cook C, Lebas E, Chow ED, Nachamkin I, Porco TC, Keenan JD, Lietman TM. Gut microbiome alteration in MORDOR I: a community-randomized trial of mass azithromycin distribution. Nat Med. 2019 Sep;25(9):1370-1376. doi: 10.1038/s41591-019-0533-0. Epub 2019 Aug 12.

  PMID: 31406349 BACKGROUND

• 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.

  PMID: 31981558 BACKGROUND

• 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

• Doan T, Worden L, Hinterwirth A, Arzika AM, Maliki R, Abdou A, Zhong L, Chen C, Cook C, Lebas E, O'Brien KS, Oldenburg CE, Chow ED, Porco TC, Lipsitch M, Keenan JD, Lietman TM. Macrolide and Nonmacrolide Resistance with Mass Azithromycin Distribution. N Engl J Med. 2020 Nov 12;383(20):1941-1950. doi: 10.1056/NEJMoa2002606.

  PMID: 33176084 BACKGROUND

• Arzika AM, Amza A, Ousmane S, Maliki R, Almou I, Galo N, Harouna N, Mankara A, Aichatou B, Boubacar O, Lebas E, Peterson B, Brandt C, Picariello A, Cheng A, Porco TC, Doan T, Arnold BF, Lietman TM, O'Brien KS. Azithromycin mass drug administration to reduce child mortality in Niger (AVENIR II): a master protocol for a cluster-randomized adaptive platform trial to evaluate community-based health interventions. medRxiv [Preprint]. 2025 Jun 18:2025.06.17.25329431. doi: 10.1101/2025.06.17.25329431.

  PMID: 40585143 DERIVED

MeSH Terms

Interventions

Azithromycin; Suspensions

Intervention Hierarchy (Ancestors)

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

Study Officials

• Kieran S O'Brien, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea R Picariello, MPH

CONTACT

609-865-4532; andrea.picariello@ucsf.edu

Elodie Lebas

CONTACT

elodie.lebas@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Participants, community health workers delivering the intervention, and team members supervising the program will not be masked. One biostatistician and one data analyst will remain unmasked to prepare the randomization sequence. Masked personnel include outcome assessors as well as the biostatistician and data analyst conducting the data analyses.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 3, 2024
• First Posted: April 11, 2024
• Study Start: April 29, 2024
• Primary Completion (Estimated): April 29, 2028
• Study Completion (Estimated): April 29, 2028
• Last Updated: June 22, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 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

NI (1)