Mortality Reduction After Oral Azithromycin: Mortality Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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Evaluating Impact of Azithromycin Mass Drug Administrations on All-cause Mortality and Antibiotic Resistance: Mortality Trial

Conditions
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Childhood Mortality

Intervention / Treatment
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* Drug: Azithromycin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Communities The community location in target district. The community leader consents to participation in the trial The community's estimated population is between 200-2,000 people. The community is not in an urban area. 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)

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 60 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Biannual mass oral azithromycin<br>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. | Drug: Azithromycin<br>* 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.<br>* Other names: Zithromax;|
| Placebo Comparator: Biannual mass oral placebo<br>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. | Drug: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause Mortality Rate in Children Aged 1-60 Months | This is a single multi-site trial, with each country as a secondary analysis. Also, an interim analysis of efficacy and futility will be conducted according to a pre-specified plan in the Statistical Analysis Plan. | 24 Months | 
| All-cause Mortality Rate in Children Aged 1-60 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. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Niger Only) | Deaths were assessed via biannual population census. A pre-specified outcome was cause of death, assessed by verbal autopsy. | 24 Months | 
| Cost-effectiveness of Mass Azithromycin Administration, Per Averted Childhood Death | Cost-effectiveness of Mass Azithromycin Administration, Per Averted Childhood Death during the 24 month phase | 24 months | 
| All-cause and Cause-specific Health Clinic Visits in 1-60 Month-old Children | We recorded clinic visits one year prior the study and during the first year of the study and collected outcomes of these visit. | 24 months | 
| Cause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Tanzania Only) | 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. | 24 Months | 
| Cause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Malawi Only) | Cause-specific mortality by intention-to-treat for the four main inferred causes of death in the study area. | 24 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Childhood mortality, Azithromycin, Mass treatment, Infection, Verbal Autopsy