Clinical trial NCT04716712: Infant Mortality Reduction by the Mass Administration of Azithromycin
Official title: Mortalite Infantile Reduite Par l'Administration de Masse de l'Azitromycine
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Child Mortality
Keywords: Azithromycin
Mass Drug Administration
Child Mortality
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Helen Keller International
name: Centre de Recherche en Sante de Nouna, Burkina Faso
name: Bill and Melinda Gates Foundation
First posted: 2021-01-20
Enrollment: 694400
Sex: ALL
Minimum age (years): 1
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: The study will be a double-blind, placebo-controlled, cluster-randomized trial in which health centers (CSPS) in the 3 intervention regions will be randomized to either CHD combined with placebo (33%) or CHD combined with Azithromycin (67%), an allocation of 1:2 that favors active treatment. The allocation sequence and treatment labels will be masked to all but one biostatistician and one analyst at UCSF. The placebo will be indistinguishable from the active azithromycin.

Antimicrobial resistance will be monitored in a parallel study of communities from the target study area. 60 communities will be randomly selected among eligible communities, and randomized in a 1 : 1 fashion to CHD+placebo or CHD+azithromycin
Primary purpose: PREVENTION

Brief summary: This trial will investigate the supplementation of azithromycin distribution to the "Child Health Days" platform in Burkina Faso for child mortality reduction. This distribution will pair door-to-door administration of vitamin A and azithromycin or placebo with acute malnutrition screening among children 1-11 months old.

Detailed description: The MORDOR clinical trial funded by the Bill \& Melinda Gates Foundation in Malawi, Tanzania, and Niger demonstrated that biannual oral azithromycin distributions to children aged 1-59 months significantly reduced child mortality. The investigators hypothesize that biannual administration of azithromycin to children aged 1-11 months will reduce mortality in this age group. The aim of the project is to demonstrate that this intervention can be scaled up and produce the same benefits on mortality as those documented in smaller, more controlled studies. Since 1986, to reduce child mortality, Burkina Faso has been administering high-dose vitamin A supplementation to children aged 6-59 months on a biannual basis through the "Child Health Days" platform. The "Child Health days" are a door-to-door distribution of vitamin A coupled with screening for acute malnutrition in children aged 6-59 months and deworming of children aged 12-59 months. This approach has been successful but expensive. A new strategy implemented since September 2017 relies on community-based health workers (CBHWs) to distribute Vitamin A in rural areas, and on community-based distributors (CDs) in urban areas. Based on expert opinion and the preliminary findings of formative research conducted by the Ministry of Health and Helen Keller International, it was agreed that the Child Health Days platform was the most appropriate platform to implement the biannual administration of azithromycin to children aged 1 to 11 months.

In this trial, mortality will be measured via complete birth history which will be collected in a subset of villages in the study area before the first treatment distribution. The study team will also conduct a baseline census of the study areas for treatment coverage estimations.

Sixty villages (30 azithromycin, 30 placebo) will contribute to the macrolide resistance outcomes, where the study team will collect rectal and nasal swabs from children 1-59 months.

Eligibility criteria: Inclusion Criteria:

Community eligibility criteria:

* Located in one of the three selected regions: SudOuest, Centre-Ouest, Hauts-Bassins
* Verbal consent of the community leader is obtained

Inclusion criteria for children:

* Aged 1 to 11 months
* Living in one of the communities participating in the study

Exclusion Criteria:

Community exclusion criteria:

• Inaccessible or unsafe for the study team

Exclusion criteria for children:

• Known allergy to macrolides

Primary outcomes:
measure: All-cause mortality
timeFrame: 24 months following baseline
Secondary outcomes:
measure: Antimicrobial Resistance (AMR)
timeFrame: 24 months
measure: Clinic Visits
timeFrame: 24 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Nouna
country: Burkina Faso
facility: Centre de Recherche en Sante de Nouna
city: Ouagadougou
country: Burkina Faso
facility: Helen Keller International
Study officials:
affiliation: University of California, San Francisco
name: Thomas Lietman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Helen Keller International
name: Georges Dimithe
role: STUDY_DIRECTOR
References:
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.