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| Name | Class |
|---|---|
| Centre de recherche et interventions en santé publique (CRISP) | UNKNOWN |
| Ministère de la Santé Publique du Niger | UNKNOWN |
| Le Programme National de Santé Oculaire | UNKNOWN |
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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.
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:
Mortality.
Antimicrobial Resistance. To determine the impact of azithromycin MDA on AMR in population- and clinic-based samples.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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 |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of clinic visits - infectious | All infectious clinic visits among children 1-59 months of age in the program catchment area during the distribution period as assessed through passive surveillance of CSI records | 2 years |
| Number of clinic visits - infectious |
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Inclusion Criteria:
CSI-level for mortality and AMR monitoring:
Individual level for mortality monitoring:
Individual-level for AMR monitoring:
Exclusion Criteria:
At the community-level:
At the individual-level:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Andrea R Picariello, MPH | Contact | 609-865-4532 | andrea.picariello@ucsf.edu | |
| Elodie Lebas | Contact | elodie.lebas@ucsf.edu |
| Name | Affiliation | Role |
|---|---|---|
| Kieran S O'Brien, PhD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Program National de Santé Oculaire | Recruiting | Niamey | Niger |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38349371 | Background | 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. | |
| 38231623 |
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De-identified data underlying outcomes publications will be made publicly available.
Data will be made available after publication of the outcomes and will be made available indefinitely.
Once made available, the data will be open access.
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| ID | Term |
|---|---|
| D017963 | Azithromycin |
| D013535 | Suspensions |
| ID | Term |
|---|---|
| D004917 | Erythromycin |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 |
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| Centre de Recherche Médicale et Sanitaire |
| OTHER |
| Bill and Melinda Gates Foundation | OTHER |
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.
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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.
|
|
All infectious clinic visits among children 1-59 months of age in the program catchment area during the distribution period as assessed through passive surveillance of CSI records |
| 4 years |
| Prevalence of Genetic Determinants of resistance - Nasopharyngeal swabs | Prevalence of genetic determinants of resistance from nasopharyngeal swabs in children 1-59 months old after 2 years of distributions, comparing the intervention and delayed arms | 2 years |
| Prevalence of Genetic Determinants of resistance - Nasopharyngeal swabs | Prevalence of genetic determinants of resistance from nasopharyngeal swabs in children 1-59 months old after 4 years of distributions, comparing the continue and stop arms | 4 years |
| Program Cost Per Dose Delivered | Program costs will be tracked using routine expenditure reporting and micro-costing activities. | 2 years |
| 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. |
| 38100110 | 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. |
| 21427395 | 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. |
| 29561511 | 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. |
| 29694816 | 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. |
| 31406349 | 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. |
| 31981558 | 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. |
| 32924384 | 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/ |
| 33176084 | 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. |
| 41709349 | Derived | 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. Trials. 2026 Feb 18;27(1):235. doi: 10.1186/s13063-026-09561-2. |
| 40585143 | Derived | 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. |
| Organic Chemicals |
| D003102 | Colloids |
| D045424 | Complex Mixtures |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |