Azithromycin for Child Survival in Niger: Mortality and Resistance Trial (AVENIR)

University of California San Francisco (UCSF)

Status and phase: Enrolling; Phase 4

Conditions: Mortality; Child, Only; Resistance Bacterial

Treatments: Drug: Azithromycin; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04224987

19-28387A

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 1,106,050 estimated patients

Sex: All

Ages: 1 to 59 months old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

1. Intervention

   At the community-level, eligibility includes:

   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)

   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:

   Inclusion criteria:

   • 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)

   Exclusion criteria:

   • Known allergy to macrolides

2. Population-based sample collections

At the community-level, eligibility includes:

Inclusion Criteria:

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

Exclusion criteria:

• 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:

Inclusion Criteria:

• 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:

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,106,050 participants in 3 patient groups, including a placebo group

Azithro 1-11

Active Comparator group

Description:

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

Treatment:

Drug: Azithromycin

Other: Placebo

Azithro 1-59

Active Comparator group

Description:

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

Treatment:

Drug: Azithromycin

Placebo

Placebo Comparator group

Description:

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

Treatment:

Other: Placebo