Trial Outcomes & Findings for Community Health Azithromycin Trial in Burkina Faso (NCT NCT03676764)

NCT ID: NCT03676764

Last Updated: 2025-02-24

Results Overview

All-cause mortality as determined by biannual census among children aged 1-59 months

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 77664 participants
• Primary outcome timeframe: 36 months
• Results posted on: 2025-02-24

Participant Flow

Unit of analysis: Cluster

Participant milestones

Measure	Biannual Mass Oral Azithromycin Bi-annual Mass Azithromycin distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit	Biannual Mass Oral Placebo Bi-annual Mass Placebo distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit Placebos: biannual placebo in eligible communities to children 1 to 59 months old Targeted placebo to children aged 5 to 8 weeks old at the vaccine visit	Targeted Oral Azithromycin Targeted azithromycin to children 5 to 12 weeks old at vaccine visit or other healthy child visit Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit	Targeted Oral Placebo Targeted placebo to children 5 to 12 weeks old at vaccine visit or other healthy child visit Placebos: biannual placebo in eligible communities to children 1 to 59 months old Targeted placebo to children aged 5 to 8 weeks old at the vaccine visit
Overall Study STARTED	22148 144	22639 140	16416 0	16461 0
Overall Study COMPLETED	19924 132	19351 126	15734 0	15701 0
Overall Study NOT COMPLETED	2224 12	3288 14	682 0	760 0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Community Health Azithromycin Trial in Burkina Faso

Baseline characteristics by cohort

Measure	Biannual Mass Oral Azithromycin n=22148 Participants Bi-annual Mass Azithromycin distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit	Biannual Mass Oral Placebo n=22639 Participants Bi-annual Mass Placebo distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit Placebos: biannual placebo in eligible communities to children 1 to 59 months old Targeted placebo to children aged 5 to 8 weeks old at the vaccine visit	Targeted Oral Azithromycin n=16416 Participants Targeted azithromycin to children 5 to 12 weeks old at vaccine visit or other healthy child visit Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit	Targeted Oral Placebo n=16461 Participants Targeted placebo to children 5 to 12 weeks old at vaccine visit or other healthy child visit Placebos: biannual placebo in eligible communities to children 1 to 59 months old Targeted placebo to children aged 5 to 8 weeks old at the vaccine visit	Total n=77664 Participants Total of all reporting groups
Age, Continuous	31 month STANDARD_DEVIATION 16.71 • n=5 Participants	31 month STANDARD_DEVIATION 16.71 • n=7 Participants	1.51 month STANDARD_DEVIATION 0.51 • n=5 Participants	1.55 month STANDARD_DEVIATION 0.51 • n=4 Participants	10 month STANDARD_DEVIATION 19.22 • n=21 Participants
Sex: Female, Male Female	10883 Participants n=5 Participants	11249 Participants n=7 Participants	8045 Participants n=5 Participants	8136 Participants n=4 Participants	38313 Participants n=21 Participants
Sex: Female, Male Male	11265 Participants n=5 Participants	11390 Participants n=7 Participants	8371 Participants n=5 Participants	8325 Participants n=4 Participants	39351 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	22148 Participants n=5 Participants	22639 Participants n=7 Participants	16416 Participants n=5 Participants	16461 Participants n=4 Participants	77664 Participants n=21 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment Burkina Faso	22148 participants n=5 Participants	22639 participants n=7 Participants	16416 participants n=5 Participants	16461 participants n=4 Participants	77664 participants n=21 Participants

PRIMARY outcome

Timeframe: 36 months

Population: Primary analysis included 34399 children in azithromycin clusters and 33847 children placebo clusters during 6 census periods. Person-time for the denominator was calculated by summing the person-time for each intercensal period. Children who were alive during both censuses contributed the person-time for that intercensal period. A cluster that was not censused, eg, due to security, could reenter the study at a later census.

All-cause mortality as determined by biannual census among children aged 1-59 months

Outcome measures

Measure	Biannual Mass Oral Azithromycin n=34399 Participants Bi-annual Mass Azithromycin distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit	Biannual Mass Oral Placebo n=33847 Participants Bi-annual Mass Placebo distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit Placebos: biannual placebo in eligible communities to children 1 to 59 months old Targeted placebo to children aged 5 to 8 weeks old at the vaccine visit
All-cause Mortality Rate in Children Aged 1-59 Months	8.2 deaths per 1000 person years	10.0 deaths per 1000 person years

PRIMARY outcome

Timeframe: 6 months

All-cause mortality as determined by a follow-up visit for individually randomized children at healthy child visits

Outcome measures

Measure	Biannual Mass Oral Azithromycin n=15734 Participants Bi-annual Mass Azithromycin distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit	Biannual Mass Oral Placebo n=15701 Participants Bi-annual Mass Placebo distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit Placebos: biannual placebo in eligible communities to children 1 to 59 months old Targeted placebo to children aged 5 to 8 weeks old at the vaccine visit
All-cause Mortality Rate in Individually Randomized Children at 4-12 Weeks of Age	82 Participants	75 Participants

SECONDARY outcome

Timeframe: 36 months

Malaria parasitemia as measured by thin and thick smears in a random sample of children at 36 months

Outcome measures

Measure	Biannual Mass Oral Azithromycin n=345 Participants Bi-annual Mass Azithromycin distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit	Biannual Mass Oral Placebo n=344 Participants Bi-annual Mass Placebo distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit Placebos: biannual placebo in eligible communities to children 1 to 59 months old Targeted placebo to children aged 5 to 8 weeks old at the vaccine visit
Malaria Parasitemia in Children 1-59 Months at 36 Months	90 Participants	114 Participants

SECONDARY outcome

Timeframe: 6 months

Population: 13641 children in Targeted oral azithromycin arm and 13657 children in Targeted oral placebo arm had valid height and weight measurement

The WHZ is calculated using weight (kg) and height (cm) measurements taken at healthy child visits and converted into Z-scores using the WHO Growth Standards. Z-scores represent the number of standard deviations from the median of a reference population.

A WHZ of 0 represents the median of the reference population, while negative Z-scores indicate below-average weight-for-height, and positive Z-scores indicate above-average weight-for-height. A WHZ below -2 is indicative of wasting, while a WHZ above +2 is considered overweight.

Outcome measures

Measure	Biannual Mass Oral Azithromycin n=13641 Participants Bi-annual Mass Azithromycin distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit	Biannual Mass Oral Placebo n=13567 Participants Bi-annual Mass Placebo distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit Placebos: biannual placebo in eligible communities to children 1 to 59 months old Targeted placebo to children aged 5 to 8 weeks old at the vaccine visit
Weight-for-height Z-score in Individually Randomized Children at Healthy Child Visits	-0.64 z-score Standard Deviation 1.2	-0.64 z-score Standard Deviation 1.2

SECONDARY outcome

Timeframe: 6 months

Population: 13641 children in Targeted oral azithromycin arm and 13657 children in Targeted oral placebo arm had valid height and weight measurement

The Height-for-age Z-score (HAZ) is calculated using height (cm) measurements taken at healthy child visits and converted into Z-scores using the WHO Growth Standards. Z-scores represent the number of standard deviations from the median of a reference population.

A HAZ of 0 represents the median of the reference population, while negative Z-scores indicate below-average height-for-age, and positive Z-scores indicate above-average height-for-age. A HAZ below -2 is indicative of stunting, reflecting chronic undernutrition or growth failure.

Outcome measures

Measure	Biannual Mass Oral Azithromycin n=13641 Participants Bi-annual Mass Azithromycin distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit	Biannual Mass Oral Placebo n=13657 Participants Bi-annual Mass Placebo distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit Placebos: biannual placebo in eligible communities to children 1 to 59 months old Targeted placebo to children aged 5 to 8 weeks old at the vaccine visit
Height-for-age Z-score in Individually Randomized Children at Healthy Child Visits	-0.31 z score Standard Deviation 1.3	-0.31 z score Standard Deviation 1.3

SECONDARY outcome

Timeframe: 6 months

Population: 13641 children in azithromycin group and 13657 children in placebo group had valid MUAC measurement at 6 month

Outcome measures

Measure	Biannual Mass Oral Azithromycin n=13641 Participants Bi-annual Mass Azithromycin distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit	Biannual Mass Oral Placebo n=13657 Participants Bi-annual Mass Placebo distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit Placebos: biannual placebo in eligible communities to children 1 to 59 months old Targeted placebo to children aged 5 to 8 weeks old at the vaccine visit
Mid-upper Arm Circumference in Individually Randomized Children at Healthy Child Visits	13.8 cm Standard Deviation 1.2	13.8 cm Standard Deviation 1.2

SECONDARY outcome

Timeframe: 6 months

Population: 13641 children in azithromycin group and 13657 children in placebo group had valid length measurement at 6 month

Change in length per day from baseline to 6 months

Outcome measures

Measure	Biannual Mass Oral Azithromycin n=13641 Participants Bi-annual Mass Azithromycin distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit	Biannual Mass Oral Placebo n=13657 Participants Bi-annual Mass Placebo distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit Placebos: biannual placebo in eligible communities to children 1 to 59 months old Targeted placebo to children aged 5 to 8 weeks old at the vaccine visit
Linear Growth in Individually Randomized Children	8.0 mm/day Standard Deviation 2.1	8.0 mm/day Standard Deviation 2.3

SECONDARY outcome

Timeframe: 6 months

Population: 13641 children in azithromycin group and 13657 children in placebo group had valid weight measurement at 6 month

Change in weight per day from baseline to 6 months

Outcome measures

Measure	Biannual Mass Oral Azithromycin n=13641 Participants Bi-annual Mass Azithromycin distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit	Biannual Mass Oral Placebo n=13657 Participants Bi-annual Mass Placebo distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit Placebos: biannual placebo in eligible communities to children 1 to 59 months old Targeted placebo to children aged 5 to 8 weeks old at the vaccine visit
Weight Gain in Individually Randomized Children	18 g/day Standard Deviation 6.2	18 g/day Standard Deviation 6.4

Adverse Events

Biannual Mass Oral Azithromycin

Serious events: 0 serious events

Other events: 77 other events

Deaths: 498 deaths

Biannual Mass Oral Placebo

Serious events: 0 serious events

Other events: 14 other events

Deaths: 588 deaths

Targeted Oral Azithromycin

Serious events: 5 serious events

Other events: 62 other events

Deaths: 82 deaths

Targeted Oral Placebo

Serious events: 1 serious events

Other events: 79 other events

Deaths: 75 deaths

Serious adverse events

Measure	Biannual Mass Oral Azithromycin n=269 participants at risk Bi-annual Mass Azithromycin distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit	Biannual Mass Oral Placebo n=199 participants at risk Bi-annual Mass Placebo distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit Placebos: biannual placebo in eligible communities to children 1 to 59 months old Targeted placebo to children aged 5 to 8 weeks old at the vaccine visit	Targeted Oral Azithromycin n=1606 participants at risk Targeted azithromycin to children 5 to 12 weeks old at vaccine visit or other healthy child visit Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit	Targeted Oral Placebo n=1532 participants at risk Targeted placebo to children 5 to 12 weeks old at vaccine visit or other healthy child visit Placebos: biannual placebo in eligible communities to children 1 to 59 months old Targeted placebo to children aged 5 to 8 weeks old at the vaccine visit
General disorders Death	0.00% 0/269 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	0.00% 0/199 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	0.00% 0/1606 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	0.07% 1/1532 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.
General disorders Hospitalization	0.00% 0/269 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	0.00% 0/199 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	0.31% 5/1606 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	0.00% 0/1532 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.

Other adverse events

Measure	Biannual Mass Oral Azithromycin n=269 participants at risk Bi-annual Mass Azithromycin distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit	Biannual Mass Oral Placebo n=199 participants at risk Bi-annual Mass Placebo distribution to all children 1-60 months old in participating communities Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit Placebos: biannual placebo in eligible communities to children 1 to 59 months old Targeted placebo to children aged 5 to 8 weeks old at the vaccine visit	Targeted Oral Azithromycin n=1606 participants at risk Targeted azithromycin to children 5 to 12 weeks old at vaccine visit or other healthy child visit Azithromycin: biannual azithromycin in eligible communities to children 1 to 59 months old Targeted azithromycin to children aged 5 to 8 weeks old at the vaccine visit	Targeted Oral Placebo n=1532 participants at risk Targeted placebo to children 5 to 12 weeks old at vaccine visit or other healthy child visit Placebos: biannual placebo in eligible communities to children 1 to 59 months old Targeted placebo to children aged 5 to 8 weeks old at the vaccine visit
Gastrointestinal disorders Diarrhea	11.2% 30/269 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	2.5% 5/199 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	2.2% 36/1606 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	2.9% 45/1532 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.
General disorders Abdominal pain	7.1% 19/269 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	3.0% 6/199 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	0.00% 0/1606 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	0.00% 0/1532 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.
Gastrointestinal disorders Vomiting	4.1% 11/269 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	0.00% 0/199 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	1.5% 24/1606 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	2.5% 38/1532 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.
Gastrointestinal disorders Constipation	3.7% 10/269 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	0.00% 0/199 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	0.56% 9/1606 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	0.91% 14/1532 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.
Gastrointestinal disorders Hemorrhoids	1.9% 5/269 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	1.5% 3/199 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	0.37% 6/1606 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	0.52% 8/1532 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.
Skin and subcutaneous tissue disorders Rash	0.74% 2/269 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	0.00% 0/199 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	0.56% 9/1606 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.	0.78% 12/1532 • For the Biannual Mass Oral Azithromycin/Placebo arm, adverse events among infants <6 months of age participating in the first treatment round in a subset of 48 study clusters. Adverse events were collected 2 weeks following the distribution of azithromycin or placebo. For Targeted Oral Azithromycin/Placebo arm, active surveillance for adverse events was performed in a random sample of 10% of enrolled infants and recorded at 2 weeks after administration of azithromycin or placebo. All-cause mortality was monitored at every census/visit in all arms. The number at risk for mortality reflects children included over the study period. Adverse events (AEs) were collected for 2 weeks post-distribution: in all selected clusters for Biannual Mass Az/Pl arms and a 10% random sample in the Targeted Az/Pl arm. The number at risk for AEs refers to children completing the 2-week follow-up, which differs from the Participant Flow module.

Additional Information

Dr. Thomas Lietman, Director of the UCSF FI Proctor Foundation

University of California, San Francisco FI Proctor Foundation

Phone: 415-476-1442

Email: tom.lietman@ucsf.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place