Azithromycin for Child Survival in Niger II

NCT ID: NCT06358872

Last Updated: 2025-06-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

3300000 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-29

Study Completion Date

2028-04-29

Brief Summary

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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

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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.

Conditions

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Mortality Antimicrobial Resistance

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
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.

Study Groups

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Continuous Distribution

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

Group Type ACTIVE_COMPARATOR

Azithromycin for Oral Suspension

Intervention Type 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.

Delayed Distribution

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

Group Type ACTIVE_COMPARATOR

Azithromycin for Oral Suspension

Intervention Type 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.

Stop Distribution

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

Group Type ACTIVE_COMPARATOR

Azithromycin for Oral Suspension

Intervention Type 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.

Interventions

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Azithromycin for Oral Suspension

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.

Intervention Type DRUG

Other Intervention Names

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Zithromax

Eligibility Criteria

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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
Minimum Eligible Age

1 Month

Maximum Eligible Age

59 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Centre de recherche et interventions en santé publique (CRISP)

UNKNOWN

Sponsor Role collaborator

Ministère de la Santé Publique du Niger

UNKNOWN

Sponsor Role collaborator

Le Programme National de Santé Oculaire

UNKNOWN

Sponsor Role collaborator

Centre de Recherche Médicale et Sanitaire

OTHER

Sponsor Role collaborator

Bill and Melinda Gates Foundation

OTHER

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kieran S O'Brien, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

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Program National de Santé Oculaire

Niamey, , Niger

Site Status RECRUITING

Countries

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Niger

Central Contacts

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Andrea R Picariello, MPH

Role: CONTACT

609-865-4532

Elodie Lebas

Role: CONTACT

Facility Contacts

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Amza Abdou, MD

Role: primary

+011 227-96-96-16-96

Ahmed Arzika

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 38349371 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 38231623 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 38100110 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21427395 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29561511 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29694816 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31406349 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31981558 (View on PubMed)

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/

Reference Type BACKGROUND
PMID: 32924384 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33176084 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40585143 (View on PubMed)

Other Identifiers

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23-39839

Identifier Type: -

Identifier Source: org_study_id

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