Antimicrobial Resistance, Mortality
Conditions
Keywords
Mass Treatment, Azithromycin, Childhood Mortality Rate, Antimicrobial Resistance, Implementation and Cost Analysis
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.
Detailed 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.
Interventions
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.
Sponsors
University of California, San Francisco
Centre de recherche et interventions en santé publique (CRISP)
Ministère de la Santé Publique du Niger
Le Programme National de Santé Oculaire
Centre de Recherche Médicale et Sanitaire
Bill and Melinda Gates Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
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.
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
1 Months to 59 Months
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-cause mortality | 2 years | 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 |
| Prevalence of resistance to macrolides - nasopharyngeal swabs | 2 years | 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 |
| Load of genetic determinants of resistance to macrolides - rectal swabs | 2 years | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of clinic visits - infectious | 2 years | 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 |
| Prevalence of Genetic Determinants of resistance - Nasopharyngeal swabs | 2 years | 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 |
| Program Cost Per Dose Delivered | 2 years | Program costs will be tracked using routine expenditure reporting and micro-costing activities. |
| Prevalence of Reported Illness | 2 years | Prevalence of caregiver reported illness among children 1-59 months of age in the program's catchment area in the 2 weeks following MDA as assessed through a household survey in a random subset of the population |
Countries
Niger
Contacts
CONTACTAndrea R Picariello, MPH
CONTACTElodie Lebas
PRINCIPAL_INVESTIGATORKieran S O'Brien, PhD
University of California, San Francisco
Outcome results
None listed