Mortality Reduction After Oral Azithromycin Contingency: Mortality Study

Study Overview
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Brief Summary
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MORDOR was a cluster-randomized placebo controlled trial that assessed the efficacy of mass azithromycin distributions for the prevention of childhood mortality. All communities were subsequently treated with mass azithromycin for one year. The present trial re-randomized communities to azithromycin or placebo for the fourth and fifth year of the study.

Detailed Description
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Pre-trial treatments: in the original MORDOR trial, communities were randomized to 4 rounds of biannual mass distributions of either azithromycin or placebo (i.e, the first two years of the trial). All communities were subsequently treated with 2 rounds of biannual mass azithromycin (i.e., the fifth and sixth rounds, during the third year of the trial). Present trial design: The present trial enrolls all communities previously enrolled in the Niger site of MORDOR, and re-randomizes communities to biannual mass distributions of either azithromycin or placebo (i.e., the seventh, eighth, ninth and tenth rounds of mass drug administration since randomization for the original MORDOR trial, occurring in the fourth and fifth year since randomization). This results in four patterns of community-based treatment: four years of azithromycin (AAAAA), three years of azithromycin followed by one year of placebo (AAAPP), two years of placebo followed by two years of azithromycin (PPAAA), and two years of placebo followed by one year of azithromycin and then one year of placebo (PPAPP). The primary outcome will be all-cause mortality in children aged 1-59 months,as determined by biannual census. The mortality rate following re-randomization (i.e., the seventh, eighth, ninth and tenth rounds of mass drug administration) will be compared between the two re-randomized groups.

Official Title
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Mortality Reduction After Oral Azithromycin Contingency: Mortality Study

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- All communities eligible for MORDOR (NCT02047981) Individuals-All children aged 1-60 months (up to but not including the 5th birthday), as assessed via biannual census Exclusion Criteria: 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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No

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Azithro<br>Communities will receive four rounds of biannual mass azithromycin. | 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<br>* Other names: Zithromax;|
| Placebo Comparator: Placebo<br>Communities will receive four rounds of biannual mass placebo. | Drug: Placebo<br>* Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo suspension every 6 months<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 | as measured by presence on census and absence on sequential census due to death | 24 months | 
| Macrolide Resistance in Children Aged 1-60 Months | as measured by nasopharyngeal swabs | 18 months | 
| Normalized Macrolide Resistance in Children Aged 1-60 Months | as measured by rectal swabs. Fraction of macrolide resistance from stool specimens in children 1-60 months (core). For Niger, this includes RNA, DNA, and TAC-card methods (a binary outcome at the individual level). | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbial Composition of Stool | as measured by Meta-genomic Deep Sequencing | 18 months | 
| Campylobacter and Other Pathogenic Organisms in Stool | as measured by molecular techniques | 18 months | 

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