Azithromycin for Child Survival in Niger: Mortality and Resistance Trial

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

864493 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-24

Study Completion Date

2024-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.Targeting treatment to children 1-11 months old could reduce antimicrobial resistance by limiting antibiotic distributions while treating children at the highest mortality risk. However, this targeted intervention has not yet been tested.

The AVENIR mortality/resistance trial aims to assess the efficacy of age-based targeting of biannual azithromycin distribution on mortality as well as determine the impact of age-based targeting on antimicrobial resistance.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Gut and Azithromycin Mechanisms in Infants and Children II

NCT04315272

Malaria

COMPLETED PHASE4

Infant Mortality Reduction by the Mass Administration of Azithromycin

NCT04716712

Child Mortality

ACTIVE_NOT_RECRUITING PHASE4

Effects of Mass Drug Administration of Azithromycin on Mortality and Other Outcomes Among 1-11 Month Old Infants in Mali

NCT04424511

Mortality

COMPLETED PHASE3

Neonates and Azithromycin, an Innovation in the Treatment of Children in Burkina Faso

NCT03682653

Childhood Mortality

COMPLETED PHASE4

Oral Azithromycin to Prevent Stillbirths and Infant Mortality in Mali

NCT03909737

Stillbirths and Infant Mortality

ACTIVE_NOT_RECRUITING PHASE4

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

In the Mortality/Resistance trial, 3,000 communities in the Dosso and Tahoua regions of Niger will be randomized to one of three arms: 1) azithro 1-11: biannual oral azithromycin to children 1-11 months old with biannual oral placebo to children 12-59 months old, 2) azithro 1-59: biannual oral azithromycin to children 1-59 months old, or 3) placebo: biannual oral placebo to children 1-59 months old. Interventions will be delivered biannually through a door-to-door census. Mortality will also be monitored through biannual census data collection, which will be used to adaptively allocate treatment assignments after the first year. Communities will retain an allocation for 4 distributions before being re-randomized.

Antimicrobial resistance will be monitored using cluster sampling of treated and untreated children and adults in the Dosso region.

To compare costs, coverage, and acceptability of treating 1-11-month-old children only vs children 1-59 months old, an additional 80 communities in the Dosso region will be selected. These communities will be randomized in a 1:1 fashion to either receive 1) distribution of open-label azithromycin to children 1-11 months old with no intervention to children 12-59 months old or 2) distribution of open-label azithromycin to children 1-59 months old. The primary outcome for this substudy will be community-level costs per dose delivered. Secondary outcomes include program costs, treatment coverage, and acceptability of the intervention according to community leaders, community health workers, and caregivers of eligible children.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Mortality Resistance Bacterial Child, Only

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The AVENIR mortality/resistance trial is a large simple double-masked cluster-randomized trial with response-adaptive allocation in Niger.

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

In the mortality/resistance trial, we will use a matching placebo to mask study arm allocation. Placebo will be identical to azithromycin in appearance, smell, and packaging. Treatment assignment will be masked by assigning a series of upper- and lower-case letters to each trial, age group, and treatment arm. Those masked to study arm allocation include participants, investigators, most study personnel including study personnel administering treatment and collecting data on mortality outcomes, and laboratory personnel processing samples for resistance outcomes. Unmasked personnel include the trial biostatistician and data analyst responsible for implementing the randomization sequence and key members of Pfizer staff.

In a subset of 80 communities, open-label azithromycin will be distributed with no masking of participants, implementors, or outcome assessors.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Azithro 1-11

Biannual weight- or height-based dose of oral azithromycin suspension to children 1-11 months old and oral placebo or no intervention to children 12-59 months old

Group Type ACTIVE_COMPARATOR

Azithromycin

Intervention Type DRUG

Azithromycin will be administered as a directly observed dose in oral suspension form for children:

1. Single-dose of 20mg/kg in children (up to the maximum adult dose of 1g)
2. For children 1-11 months of age, weight or age-based dosing will be used
3. For children 12-59 months of age, height-based dosing will be used via height-stick approximation as currently performed by Niger's trachoma program

Placebo

Intervention Type OTHER

Placebo will be administered as a directly observed dose in oral suspension form for children:

1. Single-dose of 20mg/kg in children (up to the maximum adult dose of 1g)
2. For children 1-11 months of age, weight-based dosing will be used
3. For children 12-59 months of age, height-based dosing will be used via height-stick approximation as currently performed by Niger's trachoma program

Azithro 1-59

Biannual age, weight- or height-based dose of oral azithromycin suspension to children 1-59 months old

Group Type ACTIVE_COMPARATOR

Azithromycin

Intervention Type DRUG

Azithromycin will be administered as a directly observed dose in oral suspension form for children:

1. Single-dose of 20mg/kg in children (up to the maximum adult dose of 1g)
2. For children 1-11 months of age, weight or age-based dosing will be used
3. For children 12-59 months of age, height-based dosing will be used via height-stick approximation as currently performed by Niger's trachoma program

Placebo

Biannual weight- or height-based dose of oral placebo to children 1-59 months old

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Placebo will be administered as a directly observed dose in oral suspension form for children:

1. Single-dose of 20mg/kg in children (up to the maximum adult dose of 1g)
2. For children 1-11 months of age, weight-based dosing will be used
3. For children 12-59 months of age, height-based dosing will be used via height-stick approximation as currently performed by Niger's trachoma program

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Azithromycin

Azithromycin will be administered as a directly observed dose in oral suspension form for children:

1. Single-dose of 20mg/kg in children (up to the maximum adult dose of 1g)
2. For children 1-11 months of age, weight or age-based dosing will be used
3. For children 12-59 months of age, height-based dosing will be used via height-stick approximation as currently performed by Niger's trachoma program

Intervention Type DRUG

Placebo

Placebo will be administered as a directly observed dose in oral suspension form for children:

1. Single-dose of 20mg/kg in children (up to the maximum adult dose of 1g)
2. For children 1-11 months of age, weight-based dosing will be used
3. For children 12-59 months of age, height-based dosing will be used via height-stick approximation as currently performed by Niger's trachoma program

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Zithromax

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Location in Dosso, Tahoua, Maradi, Zinder, or Tillabéri regions
* Population 250 to 2,499\*
* Distance \> 5 km from district headquarters town
* Distinguishable from neighboring communities
* Verbal consent of community leader(s)

* Age 1-59 months
* Primary residence in a study community
* Verbal consent of caregiver/guardian for study participation
* Weight ≥ 3.0 kg (\*no weight limits in communities using age-based dosing)

* Location in Dosso
* Distinguishable from neighboring communities
* Verbal consent of community leader(s)

* Age 1-59 months or 7-12 years or caregiver/guardian of a child eligible for treatment
* Primary residence in a study community selected for sample collections
* Verbal consent of caregiver/guardian for study participation

Exclusion Criteria

* Inaccessible or unsafe for study team
* "Quartier" designation on national census \*Population size as estimated from the most recent national census or projections

At the individual-level, eligibility includes:

• Known allergy to macrolides
2. Population-based sample collections

At the community-level, eligibility includes:

* Inaccessible or unsafe for the study team
* Included in MORDOR trials
* Not randomly selected
* Received treatment prior to sample collection

At the individual-level, eligibility includes:

• An individual is not on the list of randomly selected participants from the census

Minimum Eligible Age

1 Month

Maximum Eligible Age

59 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes