Azithromycin for Child Survival in Niger II

Mortality Clinical Trial

— AVENIR II  

Official title:

Azithromycine Pour la Vie Des Enfants au Niger II

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06358872
• Other study ID #: 23-39839
• Status: Recruiting
• Phase: Phase 4
• Start date: April 29, 2024
• Est. completion date: April 29, 2028

Study information

• Verified date: June 2024
• Source: University of California, San Francisco
• Contact: Andrea R Picariello, MPH
• Phone: 609-865-4532
• Email: andrea.picariello[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3300000
• Est. completion date: April 29, 2028
• Est. primary completion date: April 29, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Month to 59 Months

Eligibility

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

Related Conditions & MeSH terms

• Antimicrobial Resistance
• Mortality

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Niger	Program National de Santé Oculaire	Niamey

Sponsors (6)

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

Country where clinical trial is conducted

Niger, 

References & Publications (10)

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. — View Citation

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. — View Citation

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

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. — View 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/ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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	4 years
Secondary	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
Secondary	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
Secondary	Program Cost Per Dose Delivered	Program costs will be tracked using routine expenditure reporting and micro-costing activities.	2 years