Mortality Reduction After Oral Azithromycin Contingency: Mortality Study

Phase 4

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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)

Arm && Interventions

Group	Intervention	Description
Azithro	Azithromycin	Communities will receive four rounds of biannual mass azithromycin.
Placebo	Placebo	Communities will receive four rounds of biannual mass placebo.

Primary Outcome Measures

Name	Time	Method
All-cause Mortality Rate in Children Aged 1-60 Months	24 months	as measured by presence on census and absence on sequential census due to death
Macrolide Resistance in Children Aged 1-60 Months	18 months	as measured by nasopharyngeal swabs
Normalized Macrolide Resistance in Children Aged 1-60 Months	18 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).

Secondary Outcome Measures

Name	Time	Method
Microbial Composition of Stool	18 months	as measured by Meta-genomic Deep Sequencing
Campylobacter and Other Pathogenic Organisms in Stool	18 months	as measured by molecular techniques