Childhood Mortality
Conditions
Keywords
Childhood mortality, Mass treatment, Azithromycin, Infection
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.
Interventions
DRUGAzithromycin
Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months
DRUGPlacebo
Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo suspension every 6 months
Sponsors
The Carter Center
Bill and Melinda Gates Foundation
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 60 Months
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Niger, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Azithro Communities will receive four rounds of biannual mass azithromycin.
Azithromycin: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months | 33,173 |
| Placebo Communities will receive four rounds of biannual mass placebo.
Placebo: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo suspension every 6 months | 33,055 |
| Total | 66,228 |
Baseline characteristics
| Characteristic | Azithro | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 33173 Participants | 33055 Participants | 66228 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 33173 Participants | 33055 Participants | 66228 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Niger | 33173 participants | 33055 participants | 66228 participants |
| Sex: Female, Male Female | 16052 Participants | 16084 Participants | 32136 Participants |
| Sex: Female, Male Male | 17121 Participants | 16971 Participants | 34092 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1,493 / 33,173 | 1,584 / 33,055 |
| other Total, other adverse events | 0 / 33,173 | 0 / 33,055 |
| serious Total, serious adverse events | 0 / 33,173 | 0 / 33,055 |
Outcome results
Primary
All-cause Mortality Rate in Children Aged 1-60 Months
as measured by presence on census and absence on sequential census due to death
Time frame: 24 months
Population: Number of participants at the start of MORDOR III
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azithro | All-cause Mortality Rate in Children Aged 1-60 Months | 24.8 deaths per 1000 person years |
| Placebo | All-cause Mortality Rate in Children Aged 1-60 Months | 26.7 deaths per 1000 person years |
Primary
Macrolide Resistance in Children Aged 1-60 Months
as measured by nasopharyngeal swabs
Time frame: 18 months
Population: We did collect nasopharyngeal swabs but pooling and DNA-seq that works with rectal samples was not sensitive enough for NP samples. So we have to wait for technology to catch up to be able to report these results.
Primary
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).
Time frame: 18 months
Population: 1,004 children in total (557 from 15 placebo-treated communities and 447 from 14 azithromycin-treated communities).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Azithro | Normalized Macrolide Resistance in Children Aged 1-60 Months | 79.85 reads per million (rM) |
| Placebo | Normalized Macrolide Resistance in Children Aged 1-60 Months | 15.79 reads per million (rM) |
Secondary
Campylobacter and Other Pathogenic Organisms in Stool
as measured by molecular techniques
Time frame: 18 months
Population: Unfortunately, we didn't collect stool, so we won't be able to report this.
Secondary
Microbial Composition of Stool
as measured by Meta-genomic Deep Sequencing
Time frame: 18 months
Population: Unfortunately, we didn't collect stool, so we won't be able to report this.