Azithromycin for Child Survival in Niger II

Официальное название

Azithromycine Pour la Vie Des Enfants au Niger II

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.

Первичные конечные точки

• All-cause mortality [Срок оценки: 2 years]
• All-cause mortality [Срок оценки: 4 years]
• Prevalence of resistance to macrolides - nasopharyngeal swabs [Срок оценки: 2 years]
• Prevalence of resistance to macrolides - nasopharyngeal swabs [Срок оценки: 4 years]
• Load of genetic determinants of resistance to macrolides - rectal swabs [Срок оценки: 2 years]
• Load of genetic determinants of resistance to macrolides - rectal swabs [Срок оценки: 4 years]

Вторичные конечные точки (5)

• Number of clinic visits - infectious [Срок оценки: 2 years]
• Number of clinic visits - infectious [Срок оценки: 4 years]
• Prevalence of Genetic Determinants of resistance - Nasopharyngeal swabs [Срок оценки: 2 years]
• Prevalence of Genetic Determinants of resistance - Nasopharyngeal swabs [Срок оценки: 4 years]
• Program Cost Per Dose Delivered [Срок оценки: 2 years]

Критерии участия

Критерии включения

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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Niger · 1 центр

• Program National de Santé Oculaire — Niamey

Публикации

• 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
• 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
• 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/jam PMID 38100110
• 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
• 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
• 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
• 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
• 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. 202 PMID 31981558

Идентификаторы

NCT: NCT06358872 · 23-39839

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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