Mortality Reduction After Oral Azithromycin: Mortality Study

Phase 4

Completed

Brief Summary: Our long-term goal is to more precisely define the role of mass azithromycin treatments as an intervention for reducing childhood mortality. We propose a single multi-site (multi-country), cluster-randomized trial comparing communities randomized to oral azithromycin with those randomized to placebo. We hypothesize that mass azithromycin treatments will reduce childhood mortality.

Detailed Description: We will assess childhood mortality over three years, comparing communities where children aged 1-60 months receive biannual oral azithromycin ("Azithromycin" arm) for two years, to communities where the children receive biannual oral placebo ("Control" arm) for two years. During the third year at the Niger site only, everyone will receive azithromycin.

This is a cluster-randomized trial; at each site, communities within a contiguous area of 300,000 to 600,000 individuals will be randomized to azithromycin or placebo using simple random sampling.

Niger contingency study: In the event that mass distributions of oral azithromycin are proven to reduce mortality in 1-60 month-old children, then we will treat all communities in Niger with mass azithromycin distributions to test whether the intervention continues to reduce childhood mortality after the initial 2 years of mass treatments.

Recruitment & Eligibility

Inclusion Criteria

Communities

Individuals - All children aged 1-60 months (up to but not including the 5th birthday), as assessed via biannual census.

Exclusion Criteria

Individuals

Refusal of village chief (for village inclusion), or refusal of parent or guardian (for individual inclusion)

Arm && Interventions

Group	Intervention	Description
Biannual mass oral placebo	Placebo	Comparison of childhood mortality in communities randomized to azithromycin versus communities randomized to placebo. Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo every 6 months for 2 years In Niger during year 3, all communities will be offered azithroymcin.
Biannual mass oral azithromycin	Azithromycin	Comparison of childhood mortality in communities randomized to azithromycin versus communities randomized to placebo. Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months for 2 years. In Niger during year 3, all communities will be offered azithroymcin.

Primary Outcome Measures

Name	Time	Method
All-cause Mortality Rate in Children Aged 1-60 Months	36 months	This was a pre-specified contingency study in Niger only in which all communities were treated with mass azithromycin during the third year of the study following the primary 24-month endpoint.

Secondary Outcome Measures

Name	Time	Method
Cause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Niger Only)	24 Months	Deaths were assessed via biannual population census. A pre-specified outcome was cause of death, assessed by verbal autopsy.
Cost-effectiveness of Mass Azithromycin Administration, Per Averted Childhood Death	24 months	Cost-effectiveness of Mass Azithromycin Administration, Per Averted Childhood Death during the 24 month phase
All-cause and Cause-specific Health Clinic Visits in 1-60 Month-old Children	24 months	We recorded clinic visits one year prior the study and during the first year of the study and collected outcomes of these visit.
Cause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Tanzania Only)	24 Months	At 6-monthly intervals a census of the communities was conducted, and for child deaths a verbal autopsy was performed to ascertain the cause using a standardized diagnostic classification. Mortality due to pneumonia or diarrhea by age group and arm are shown in the outcome measure data table below.
Cause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Malawi Only)	24 Months	Cause-specific mortality by intention-to-treat for the four main inferred causes of death in the study area.

Locations (6): College of Medicine at the University of Malawi, Blantyre
🇲🇼
Blantyre, Malawi
London School of Hygiene & Tropical Medicine
🇬🇧
London, United Kingdom
The Carter Center, Niger
🇳🇪
Niamey, Niger
Kongwa Trachoma Project
🇹🇿
Kongwa, Tanzania
UCSF Proctor Foundation
🇺🇸
San Francisco, California, United States
Johns Hopkins University
🇺🇸
Baltimore, Maryland, United States