Child Health, Implementation, Morality, Resistance Bacterial
Conditions
Brief summary
The MORDOR trial found that biannual distribution of azithromycin to children 1-59 months old reduced child mortality. The World Health Organization (WHO) released conditional guidelines for this intervention, which include targeting azithromycin distributions to children 1-11 months of age in high mortality settings. The proposed trial aims to demonstrate and evaluate large-scale implementation of azithromycin to children aged 1-11 months old in the context of a programmatic setting while monitoring mortality and resistance antimicrobial resistance.
Detailed description
In the Programmatic Trial, community health centers (also known as CSIs or Centres de Santé Intégrés) will be randomized to one of two arms: 1) programmatic azithro 1-11: biannual oral azithromycin administration to children aged 1-11 months distributed by community health workers or 2) no intervention: no distribution of azithromycin. A total of 2,490 communities within selected CSIs will be included . All communities in both arms receive routine health services offered by community health workers working for the Niger Ministry of Health's community health program. Mortality will be monitored through birth histories. Mortality and morbidity will also be monitored using routinely collected community and clinic visit data. Antimicrobial resistance will be monitored in a subset of eligible CSIs.
Interventions
Azithromycin will be administered as a single dose in oral suspension form for children (up to the maximum adult dose of 1g). Dosage will be calculated by age for children aged 1-5 months. For children 6-59 months of age, height-based dosing will be used via height-stick approximation as currently performed by Niger's trachoma program.
Sponsors
Bill and Melinda Gates Foundation
Ministry of Health, Niger
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Participants, investigators, and program implementers will not be actively masked from the study arm allocation given that no placebo will be used. Outcome assessors and data analysts will be masked.
Intervention model description
Cluster-randomized trial with response adaptive allocation
Eligibility
Sex/Gender
ALL
Age
1 Months to No maximum
Healthy volunteers
Yes
Inclusion criteria
Intervention At the community-level, eligibility includes: Inclusion Criteria: * Location in Dosso, Tahoua, Maradi, Zinder, or Tillabéri regions * Distinguishable from neighboring communities * Verbal consent of community leader(s)
Exclusion criteria
* Inaccessible or unsafe for study team * Quartier designation on national census At the individual-level, eligibility includes: Inclusion criteria: * Age 1-11 months * Primary residence in a study community * Verbal consent of caregiver/guardian for study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of Genetic Determinants of Macrolide Resistance From Population-based Samples | 2 years | Prevalence of genetic determinants of macrolide resistance including those determinants known to be found in Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus in nasopharyngeal swabs in children aged 1-59 months from population-based samples after 1 year of distribution |
| Load of Genetic Determinants of Macrolide Resistance From Population-based Samples | 2 years | Load of genetic determinants of resistance to macrolides including those determinants known to be found in Campylobacter spp, Salmonella spp, Shigella spp, and Escherichia coli from rectal swabs in children 1-59 months old from population-based samples, defined as read number per million base pairs, using DNA-seq (metagenomic deep sequencing). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of Genetic Determinants of Macrolide Resistance From Clinic-based Samples | 2 years | Prevalence of resistance to macrolides including those determinants known to be found in Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus from nasopharyngeal swabs in children 1-59 months old. |
| Load of Genetic Determinants of Macrolide Resistance From Clinic-based Samples | 2 years | Load of genetic determinants of resistance to macrolides including those determinants known to be found in Campylobacter spp, Salmonella spp, Shigella spp, and Escherichia coli from rectal swabs in children 1-59 months old, defined as read number per million base pairs, using DNA-seq (metagenomic deep sequencing). |
| Number of All-cause Clinic Visits | 2 years | Number of all-cause clinic visits per month for children aged 1-59 months over 1 year |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Programmatic Azithro 1-11 Biannual oral azithromycin administration to children aged 1-11 months distributed by community health workers
Azithromycin for Oral Suspension: Azithromycin will be administered as a single dose in oral suspension form for children (up to the maximum adult dose of 1g).
Dosage will be calculated by age for children aged 1-5 months. For children 6-59 months of age, height-based dosing will be used via height-stick approximation as currently performed by Niger's trachoma program. | 135 |
| No Intervention No additional intervention. | 33 |
| Total | 168 |
Baseline characteristics
| Characteristic | Programmatic Azithro 1-11 | No Intervention | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 135,754 Participants | 33,953 Participants | 169707 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Niger | 135,754 Participants | 33,953 Participants | 169707 Participants |
| Sex: Female, Male Female | — | — | 0 Participants |
| Sex: Female, Male Male | — | — | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 135,754 | 0 / 33,953 |
| other Total, other adverse events | 0 / 135,754 | 0 / 33,953 |
| serious Total, serious adverse events | 0 / 135,754 | 0 / 33,953 |
Outcome results
Primary
Load of Genetic Determinants of Macrolide Resistance From Population-based Samples
Load of genetic determinants of resistance to macrolides including those determinants known to be found in Campylobacter spp, Salmonella spp, Shigella spp, and Escherichia coli from rectal swabs in children 1-59 months old from population-based samples, defined as read number per million base pairs, using DNA-seq (metagenomic deep sequencing).
Time frame: 2 years
Population: The study stopped prior to the collection of outcome measures.
Primary
Prevalence of Genetic Determinants of Macrolide Resistance From Population-based Samples
Prevalence of genetic determinants of macrolide resistance including those determinants known to be found in Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus in nasopharyngeal swabs in children aged 1-59 months from population-based samples after 1 year of distribution
Time frame: 2 years
Population: The study stopped prior to the collection of outcome measures.
Secondary
Load of Genetic Determinants of Macrolide Resistance From Clinic-based Samples
Load of genetic determinants of resistance to macrolides including those determinants known to be found in Campylobacter spp, Salmonella spp, Shigella spp, and Escherichia coli from rectal swabs in children 1-59 months old, defined as read number per million base pairs, using DNA-seq (metagenomic deep sequencing).
Time frame: 2 years
Population: The study stopped prior to the collection of outcome measures.
Secondary
Number of All-cause Clinic Visits
Number of all-cause clinic visits per month for children aged 1-59 months over 1 year
Time frame: 2 years
Population: The study stopped prior to the collection of outcome measures.
Secondary
Prevalence of Genetic Determinants of Macrolide Resistance From Clinic-based Samples
Prevalence of resistance to macrolides including those determinants known to be found in Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus from nasopharyngeal swabs in children 1-59 months old.
Time frame: 2 years
Population: The study stopped prior to the collection of outcome measures.