Childhood MortalityPhase 4CHATNCT03676764
Community Health Azithromycin Trial in Burkina Faso
A Phase 4 study testing Azithromycin in people with Childhood Mortality, run by University of California, San Francisco at 1 site in Burkina Faso.
Trial summary
An estimated 7.7 million pre-school aged children die each year, the majority from infectious diseases. Mass azithromycin distributions for trachoma may have the unintended benefit of reducing childhood mortality. Read more about this study
- Who is it for?
- Ages 1 month to 59 monthsHealthy volunteers can take part
- Conditions the study is for
- Childhood Mortality
- What is being tested?
- Azithromycin
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 77,664 participants
- Where
- 1 siteBurkina Faso
- Study dates
- 1 Aug 2019to 1 Dec 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 59 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- The community location in target district.
- The community leader consents to participation in the trial (this does not obviate the need for individual consent, but without overall leadership consent, the community as a whole cannot be part of the trial).
- Eligible communities estimated population of between 200-2,000 people
- The community is not in an urban area
- All children in the study communities aged 5 to 12 weeks old at the time of the vaccination visit are eligible to participate
- Ability to feed orally
- Appropriate consent from at least one caregiver
- Family intends to stay within the study area
Who cannot join
- Refusal of village chief
- Individuals:
- Individuals allergic to macrolides or azalides will not be given the study antibiotic azithromycin, but will be included in the outcome
- Refusal of parent or guardian
- Child unable to orally feed
- Family planning to move
- Children younger than 28 days old or older than 12 weeks
- Children in the bi annual drug administration group who weight less than 3.8kg.
Trial locations and contacts
1 site in 1 country.
About this study
An estimated 7.7 million pre-school aged children die each year, the majority from infectious diseases. Mass azithromycin distributions for trachoma may have the unintended benefit of reducing childhood mortality. We recently demonstrated the biannual mass azithromycin distribution significantly reduces all-cause child mortality in a cluster randomized trial (MORDOR I) conducted in three diverse regions of Sub-Saharan Africa.
Our long-term goal is to more precisely define the role of mass azithromycin treatments as an intervention for reducing childhood morbidity and mortality. We propose a cluster randomized trial designed to repeat the original study to confirm the original results in a different geographic study with similarly high child mortality, and to better understand the mechanism behind any effect of azithromycin on child mortality. We hypothesize that biannual mass azithromycin distribution will reduce child mortality compared to placebo, and that this effect will be primarily driven by a reduction in infectious burden.
Read more
Objectives:
- Determine the efficacy of biannual mass azithromycin distribution versus placebo in children aged 1-59 months for reduction in all-cause mortality.
- Determine the efficacy of targeted azithromycin distribution to infants during an early infant healthcare visit (approximately 5th through 12th week of life) on infant mortality.
- Determine the mechanism behind the effect of biannual mass azithromycin distribution for reduction in child mortality.
The study will be conducted in the Nouna District in northwestern Burkina Faso.
Read the detailed description
Although child health and mortality are improving worldwide, children in the Sahel and sub-Sahel regions of West Africa have the greatest risks of mortality.Burkina Faso's current under-5 mortality rate is estimated 110 per 1,000 live births. Similar to other countries in the region, the major causes of child mortality in Burkina Faso are malaria, respiratory tract infection, and diarrhea. Malnutrition acts as a major underlying contributor to mortality. Interventions that address these underlying causes may be particularly efficacious for reducing mortality.
Younger children at are at a higher risk of mortality. Approximately 2/3rd of under-5 deaths occur during the first year of life. In general, the child mortality rate decreases as age increases. While some improvement has been observed, neonatal mortality is declining at a slower rate than post-neonatal childhood mortality. Many child health interventions are designed specifically for children over 6 months of age, such as vitamin A supplementation, seasonal malaria chemoprevention, and lipid-based nutritional supplementation. Identification of strategies that are safe and effective for the youngest children will be required to address persistently high rates of neonatal and infant mortality.
The MORDOR I study demonstrated a significant reduction in all-cause child mortality following biannual mass azithromycin distribution. Across three diverse geographic locations in sub-Saharan Africa (Malawi, Niger, and Tanzania), biannual mass azithromycin distribution over a two-year period led to a 14% decrease in all-cause child mortality. In Niger, 1 in 5-6 deaths were averted. These results are qualitatively similar to those of a previous study of mass azithromycin distribution for trachoma control in Ethiopia, which found reduced odds of all-cause mortality in children in communities receiving mass azithromycin compared to control communities.
In MORDOR I, the strongest effect of azithromycin was in the youngest cohort of children. Across all three countries, the strongest effect of azithromycin was consistently in children 1-5 months of age, with an approximately 25% reduction in all-cause mortality. However, MORDOR I was not optimized to target the youngest age groups. Although children as young as 1 month were eligible, biannual distributions might not reach some children until 7 months of age. On average, children were first treated at 4 months. Given that there may be a substantial benefit to treating children at younger ages, azithromycin strategies that are designed to target younger age groups may be even more beneficial for reducing child mortality.
Here, we propose a randomized controlled trial designed to evaluate the efficacy of mass and targeted azithromycin strategies for child mortality. In the rural northwestern district of Nouna in Burkina Faso, we propose to randomize villages to biannual mass azithromycin distribution or placebo. This study was designed by CRSN and UCSF partners to confirm the results of MORDOR I, evaluate an alternative health systems distribution point (the vaccine visit) for delivery of azithromycin to young children, and to provide a platform for evaluation of potential mechanisms behind the effect of azithromycin by collecting and processing additional specimens and tests.
Objectives:
- Determine the efficacy of biannual mass azithromycin distribution versus placebo in children aged 1-59 months for reduction in all-cause mortality.
- Determine the efficacy of targeted azithromycin distribution to infants during an early infant healthcare visit (approximately 5th through 12th week of life) on infant mortality.
- Determine the mechanism behind the effect of biannual mass azithromycin distribution for reduction in child mortality.
Study Design:
CRSN and UCSF (hereafter, "we") will assess childhood mortality over three years, comparing communities where children aged 1-59 months receive biannual oral azithromycin and/or targeted azithromycin during the 5th-12th week of life in conjunction with the first Expanded Programme on Immunization (EPI) vaccine visit or biannual placebo and targeted placebo. All eligible communities in Nouna District will be randomized (278 communities). A random sample of 48 (12/arm) communities from within the HDSS will be selected to participate in the "Mortality Plus" study, which will entail an annual morbidity exam among 15 randomly selected children per community to monitor infectious disease morbidity, nutritional status, and macrolide resistance. All communities will contribute to the mortality outcome.
- Conditions
- Childhood Mortality
- Being tested
- Azithromycin, Placebos
- Keywords
- Childhood mortality, Azithromycin, Mass treatment, Vaccine Visit targeted treatment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzithromycinDrug
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
PlacebosDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Biannual mass oral azithromycin | Active comparator | Bi-annual Mass Azithromycin distribution to all children 1-60 months old in participating communities Receives: Drug: Azithromycin |
| Biannual mass oral placebo | Placebo comparator | Bi-annual Mass Placebo distribution to all children 1-60 months old in participating communities Receives: Drug: Azithromycin; Drug: Placebos |
| Targeted oral placebo | Placebo comparator | Targeted placebo to children 5 to 12 weeks old at vaccine visit or other healthy child visit Receives: Drug: Placebos |
| Targeted oral azithromycin | Active comparator | Targeted azithromycin to children 5 to 12 weeks old at vaccine visit or other healthy child visit Receives: Drug: Azithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause Mortality Rate in Children Aged 1-59 Months
All-cause mortality as determined by biannual census among children aged 1-59 months
Measured: 36 months
All-cause Mortality Rate in Individually Randomized Children at 4-12 Weeks of Age
All-cause mortality as determined by a follow-up visit for individually randomized children at healthy child visits
Measured: 6 months
Secondary outcomes (6)
Malaria Parasitemia in Children 1-59 Months at 36 Months
Malaria parasitemia as measured by thin and thick smears in a random sample of children at 36 months
Measured: 36 months
Weight-for-height Z-score in Individually Randomized Children at Healthy Child Visits
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.
Measured: 6 months
Height-for-age Z-score in Individually Randomized Children at Healthy Child Visits
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.
Measured: 6 months
Mid-upper Arm Circumference in Individually Randomized Children at Healthy Child Visits
Measured: 6 months
Linear Growth in Individually Randomized Children
Change in length per day from baseline to 6 months
Measured: 6 months
Weight Gain in Individually Randomized Children
Change in weight per day from baseline to 6 months
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2018
- Study start1 Aug 2019
- Primary completion1 Dec 2023
- Study completion1 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Childhood MortalityStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- All eligible communities in Nouna District will be randomized in a 1:1 fashion to biannual azithromycin or placebo. Targeted treatment (vaccine visit) will be randomized 1:1 individually to azithromycin or placebo. Randomization will be conducted by T. Porco. Procedural and algorithmic details are provided in an appendix to the Statistical Analysis Plan.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 77,664 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Centre de Recherche en Sante de Nouna, Burkina Faso, Bill and Melinda Gates Foundation
- Responsible party
- Sponsor
- Investigators
- Catherine E Oldenburg, PhD, Principal investigator, University of California, San FranciscoTom M Lietman, MD, Principal investigator, University of California, San FranciscoAli Sie, MD, PhD, Principal investigator, Centre de Recherche en Sante de Nouna, Burkina Faso
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03676764
- Sponsor's protocol ID
- OPP1187628-A
- Acronym
- CHAT
- Status last verified
- Feb 2025
- First submitted
- 17 Sep 2018
- Last updated
- 24 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified data will be available as per the Bill and Melinda Gates open access policy. Community based data will be available that underline the reported results (texts, tables, figures, and appendices). The study protocol and statistical analysis plan will also be made available. The data will be available following publication in accordance with the BMGF guidelines
Publications
Ouattara M, Hu H, Bountogo M, Coulibaly B, Boudo V, Compaore G, Dah C, Lebas E, O'Brien KS, Arnold BF, Lietman TM, Sie A, Oldenburg CE. Mass azithromycin distribution and nutritional status among children aged 1-59 months: A secondary analysis of a cluster randomized trial. PLOS Glob Public Health. 2026 Oct 13;6(10):e0007473. doi: 10.1371/journal.pgph.0007473. eCollection 2026.
PubMed 42868154Hu H, Ouattara M, Bountogo M, Boudo V, Ouedraogo T, Dah C, Lebas E, Barnighausen T, Arnold BF, O'Brien KS, Lietman TM, Sie A, Oldenburg CE. Effect of eligibility for referral following mass screening for severe acute malnutrition using mid-upper arm circumference: A prospective regression discontinuity design. PLoS One. 2026 Oct 8;21(10):e0359729. doi: 10.1371/journal.pone.0359729. eCollection 2026.
PubMed 42848778Gebreegziabher EA, Sie A, Ouattara M, Bountogo M, Coulibaly B, Boudo V, Ouedraogo T, Lebas E, Hu H, Ante-Testard PA, Gregorich SE, O'Brien KS, Hsiang MS, Glidden DV, Arnold BF, Lietman TM, Oldenburg CE. Exploring heterogeneity in treatment effects: The impact and interaction of asset-based wealth and mass azithromycin distribution on child mortality. PLoS One. 2026 Feb 9;21(2):e0341665. doi: 10.1371/journal.pone.0341665. eCollection 2026.
PubMed 41662252Oldenburg CE, Coulibaly B, Sie A, Ouattara M, Bountogo M, Compaore G, Kiemde D, Compaore A, Zonou G, Hinterwirth A, Zhong L, Chen C, Liu Y, Yu D, Abraham T, Lebas E, Hu H, Hilde-Jones M, Arnold BF, Doan T, Lietman TM. Macrolide and Nonmacrolide Resistance After 36 Months of Mass Azithromycin Distribution in Burkina Faso: A Cluster Randomized Trial. Clin Infect Dis. 2026 Jul 8;82(6):946-953. doi: 10.1093/cid/ciag051.
PubMed 41626759Bountogo M, Ouattara M, Dah C, Coulibaly B, Ouedraogo T, Zakane A, Boudo V, Lebas E, Hu H, Arnold BF, Lietman TM, Sie A, Oldenburg CE. Azithromycin for infants at risk of poor growth and development: A pooled secondary analysis of two randomized controlled trials. PLoS One. 2025 Aug 8;20(8):e0328208. doi: 10.1371/journal.pone.0328208. eCollection 2025.
PubMed 40779591Gebreegziabher EA, Sie A, Ouattara M, Bountogo M, Coulibaly B, Boudo V, Ouedraogo T, Lebas E, Hu H, Ante-Testard PA, Gregorich SE, O'Brien KS, Hsiang MS, Glidden DV, Arnold BF, Lietman TM, Oldenburg CE. Exploring Heterogeneity in Treatment Effects: The Impact and Interaction of Asset-Based Wealth and Mass Azithromycin Distribution on Child Mortality. medRxiv [Preprint]. 2025 Jul 6:2025.07.05.25329685. doi: 10.1101/2025.07.05.25329685.
PubMed 40630579Gebreegziabher EA, Ouattara M, Bountogo M, Coulibaly B, Boudo V, Ouedraogo T, Lebas E, Hu H, O'Brien KS, Hsiang MS, Glidden DV, Arnold BF, Lietman TM, Sie A, Oldenburg CE. The role of Seasonal Malaria Chemoprevention in the effect of Azithromycin on Child Mortality: A Secondary Analysis of the CHAT Cluster Randomized Clinical Trial. medRxiv [Preprint]. 2025 May 2:2025.04.30.25326740. doi: 10.1101/2025.04.30.25326740.
PubMed 40343013Sie A, Ouattara M, Bountogo M, Boudo V, Ouedraogo T, Dah C, Compaore G, Lebas E, Hu H, Porco TC, Arnold BF, O'Brien KS, Lietman TM, Oldenburg CE. Mass azithromycin for prevention of child mortality among children with acute malnutrition: A subgroup analysis of a cluster randomized controlled trial. PLOS Glob Public Health. 2024 Oct 28;4(10):e0003875. doi: 10.1371/journal.pgph.0003875. eCollection 2024.
PubMed 39466816Oldenburg CE, Ouattara M, Bountogo M, Boudo V, Ouedraogo T, Compaore G, Dah C, Zakane A, Coulibaly B, Bagagnan C, Hu H, O'Brien KS, Nyatigo F, Keenan JD, Doan T, Porco TC, Arnold BF, Lebas E, Sie A, Lietman TM. Mass Azithromycin Distribution to Prevent Child Mortality in Burkina Faso: The CHAT Randomized Clinical Trial. JAMA. 2024 Feb 13;331(6):482-490. doi: 10.1001/jama.2023.27393.
PubMed 38349371Sie A, Ouattara M, Bountogo M, Dah C, Ouedraogo T, Boudo V, Lebas E, Hu H, Arnold BF, O'Brien KS, Lietman TM, Oldenburg CE. Single-dose azithromycin for infant growth in Burkina Faso: Prespecified secondary anthropometric outcomes from a randomized controlled trial. PLoS Med. 2024 Jan 23;21(1):e1004345. doi: 10.1371/journal.pmed.1004345. eCollection 2024 Jan.
PubMed 38261579Sie A, Ouattara M, Bountogo M, Boudo V, Ouedraogo T, Compaore G, Dah C, Bagagnan C, Lebas E, Hu H, Rice J, Porco TC, Arnold BF, Lietman TM, Oldenburg CE. Azithromycin during Routine Well-Infant Visits to Prevent Death. N Engl J Med. 2024 Jan 18;390(3):221-229. doi: 10.1056/NEJMoa2309495.
PubMed 38231623Sie A, Ouattara M, Bountogo M, Bagagnan C, Coulibaly B, Boudo V, Lebas E, Brogdon JM, Lin Y, Barnighausen T, Porco TC, Doan T, Lietman TM, Oldenburg CE; Etude CHAT Study Group. A double-masked placebo-controlled trial of azithromycin to prevent child mortality in Burkina Faso, West Africa: Community Health with Azithromycin Trial (CHAT) study protocol. Trials. 2019 Dec 4;20(1):675. doi: 10.1186/s13063-019-3855-9.
PubMed 31801563
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Community Health Azithromycin Trial in Burkina Faso
- ClinicalTrials.gov ID
- NCT03676764
- Acronym / sponsor ID
- CHAT / OPP1187628-A
- Conditions
- Childhood Mortality
- Keywords
- Childhood mortality, Azithromycin, Mass treatment, Vaccine Visit targeted treatment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 77,664 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Centre de Recherche en Sante de Nouna, Burkina Faso, Bill and Melinda Gates Foundation
- Study start
- 1 Aug 2019 (actual)
- Primary completion
- 1 Dec 2023 (actual)
- Study completion
- 1 Dec 2023 (actual)
- First posted
- 19 Sep 2018 (actual)
- Results
- Posted 24 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An estimated 7.7 million pre-school aged children die each year, the majority from infectious diseases. Mass azithromycin distributions for trachoma may have the unintended benefit of reducing childhood mortality. We recently demonstrated the biannual mass azithromycin distribution significantly reduces all-cause child mortality in a cluster randomized trial (MORDOR I) conducted in three diverse regions of Sub-Saharan Africa.
Our long-term goal is to more precisely define the role of mass azithromycin treatments as an intervention for reducing childhood morbidity and mortality. We propose a cluster randomized trial designed to repeat the original study to confirm the original results in a different geographic study with similarly high child mortality, and to better understand the mechanism behind any effect of azithromycin on child mortality. We hypothesize that biannual mass azithromycin distribution will reduce child mortality compared to placebo, and that this effect will be primarily driven by a reduction in infectious burden.
Objectives:
- Determine the efficacy of biannual mass azithromycin distribution versus placebo in children aged 1-59 months for reduction in all-cause mortality.
- Determine the efficacy of targeted azithromycin distribution to infants during an early infant healthcare visit (approximately 5th through 12th week of life) on infant mortality.
- Determine the mechanism behind the effect of biannual mass azithromycin distribution for reduction in child mortality.
The study will be conducted in the Nouna District in northwestern Burkina Faso.
Detailed description
Although child health and mortality are improving worldwide, children in the Sahel and sub-Sahel regions of West Africa have the greatest risks of mortality.Burkina Faso's current under-5 mortality rate is estimated 110 per 1,000 live births. Similar to other countries in the region, the major causes of child mortality in Burkina Faso are malaria, respiratory tract infection, and diarrhea. Malnutrition acts as a major underlying contributor to mortality. Interventions that address these underlying causes may be particularly efficacious for reducing mortality.
Younger children at are at a higher risk of mortality. Approximately 2/3rd of under-5 deaths occur during the first year of life. In general, the child mortality rate decreases as age increases. While some improvement has been observed, neonatal mortality is declining at a slower rate than post-neonatal childhood mortality. Many child health interventions are designed specifically for children over 6 months of age, such as vitamin A supplementation, seasonal malaria chemoprevention, and lipid-based nutritional supplementation. Identification of strategies that are safe and effective for the youngest children will be required to address persistently high rates of neonatal and infant mortality.
The MORDOR I study demonstrated a significant reduction in all-cause child mortality following biannual mass azithromycin distribution. Across three diverse geographic locations in sub-Saharan Africa (Malawi, Niger, and Tanzania), biannual mass azithromycin distribution over a two-year period led to a 14% decrease in all-cause child mortality. In Niger, 1 in 5-6 deaths were averted. These results are qualitatively similar to those of a previous study of mass azithromycin distribution for trachoma control in Ethiopia, which found reduced odds of all-cause mortality in children in communities receiving mass azithromycin compared to control communities.
In MORDOR I, the strongest effect of azithromycin was in the youngest cohort of children. Across all three countries, the strongest effect of azithromycin was consistently in children 1-5 months of age, with an approximately 25% reduction in all-cause mortality. However, MORDOR I was not optimized to target the youngest age groups. Although children as young as 1 month were eligible, biannual distributions might not reach some children until 7 months of age. On average, children were first treated at 4 months. Given that there may be a substantial benefit to treating children at younger ages, azithromycin strategies that are designed to target younger age groups may be even more beneficial for reducing child mortality.
Here, we propose a randomized controlled trial designed to evaluate the efficacy of mass and targeted azithromycin strategies for child mortality. In the rural northwestern district of Nouna in Burkina Faso, we propose to randomize villages to biannual mass azithromycin distribution or placebo. This study was designed by CRSN and UCSF partners to confirm the results of MORDOR I, evaluate an alternative health systems distribution point (the vaccine visit) for delivery of azithromycin to young children, and to provide a platform for evaluation of potential mechanisms behind the effect of azithromycin by collecting and processing additional specimens and tests.
Objectives:
- Determine the efficacy of biannual mass azithromycin distribution versus placebo in children aged 1-59 months for reduction in all-cause mortality.
- Determine the efficacy of targeted azithromycin distribution to infants during an early infant healthcare visit (approximately 5th through 12th week of life) on infant mortality.
- Determine the mechanism behind the effect of biannual mass azithromycin distribution for reduction in child mortality.
Study Design:
CRSN and UCSF (hereafter, "we") will assess childhood mortality over three years, comparing communities where children aged 1-59 months receive biannual oral azithromycin and/or targeted azithromycin during the 5th-12th week of life in conjunction with the first Expanded Programme on Immunization (EPI) vaccine visit or biannual placebo and targeted placebo. All eligible communities in Nouna District will be randomized (278 communities). A random sample of 48 (12/arm) communities from within the HDSS will be selected to participate in the "Mortality Plus" study, which will entail an annual morbidity exam among 15 randomly selected children per community to monitor infectious disease morbidity, nutritional status, and macrolide resistance. All communities will contribute to the mortality outcome.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- All eligible communities in Nouna District will be randomized in a 1:1 fashion to biannual azithromycin or placebo. Targeted treatment (vaccine visit) will be randomized 1:1 individually to azithromycin or placebo. Randomization will be conducted by T. Porco. Procedural and algorithmic details are provided in an appendix to the Statistical Analysis Plan.
| Arm | Type | Receives |
|---|---|---|
| Biannual mass oral azithromycin | Active comparator | Drug: AzithromycinBi-annual Mass Azithromycin distribution to all children 1-60 months old in participating communities |
| Biannual mass oral placebo | Placebo comparator | Drug: Azithromycin, Drug: PlacebosBi-annual Mass Placebo distribution to all children 1-60 months old in participating communities |
| Targeted oral placebo | Placebo comparator | Drug: PlacebosTargeted placebo to children 5 to 12 weeks old at vaccine visit or other healthy child visit |
| Targeted oral azithromycin | Active comparator | Drug: AzithromycinTargeted azithromycin to children 5 to 12 weeks old at vaccine visit or other healthy child visit |
Who may qualify
- Ages
- 1 month to 59 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- The community location in target district.
- The community leader consents to participation in the trial (this does not obviate the need for individual consent, but without overall leadership consent, the community as a whole cannot be part of the trial).
- Eligible communities estimated population of between 200-2,000 people
- The community is not in an urban area
- All children in the study communities aged 5 to 12 weeks old at the time of the vaccination visit are eligible to participate
Key exclusion criteria (8 listed)
- Refusal of village chief
- Individuals allergic to macrolides or azalides will not be given the study antibiotic azithromycin, but will be included in the outcome
- Refusal of parent or guardian
- Child unable to orally feed
- Family planning to move
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Azithromycinbiannual 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 | Drug | Biannual mass oral azithromycin, Biannual mass oral placebo, Targeted oral azithromycin |
| Placebosbiannual 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 | Drug | Biannual mass oral placebo, Targeted oral placebo |
Primary outcome
All-cause Mortality Rate in Children Aged 1-59 Months
Time frame: 36 months
All-cause mortality as determined by biannual census among children aged 1-59 months
All-cause Mortality Rate in Individually Randomized Children at 4-12 Weeks of Age
Time frame: 6 months
All-cause mortality as determined by a follow-up visit for individually randomized children at healthy child visits
6 secondary outcomes
Malaria Parasitemia in Children 1-59 Months at 36 Months
Time frame: 36 months
Weight-for-height Z-score in Individually Randomized Children at Healthy Child Visits
Time frame: 6 months
Height-for-age Z-score in Individually Randomized Children at Healthy Child Visits
Time frame: 6 months
Mid-upper Arm Circumference in Individually Randomized Children at Healthy Child Visits
Time frame: 6 months
Linear Growth in Individually Randomized Children
Time frame: 6 months
Weight Gain in Individually Randomized Children
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42868154Ouattara M, Hu H, Bountogo M, Coulibaly B, Boudo V, Compaore G, Dah C, Lebas E, O'Brien KS, Arnold BF, Lietman TM, Sie A, Oldenburg CE. Mass azithromycin distribution and nutritional status among children aged 1-59 months: A secondary analysis of a cluster randomized trial. PLOS Glob Public Health. 2026 Oct 13;6(10):e0007473. doi: 10.1371/journal.pgph.0007473. eCollection 2026.
- Derived from this study: PubMed 42848778Hu H, Ouattara M, Bountogo M, Boudo V, Ouedraogo T, Dah C, Lebas E, Barnighausen T, Arnold BF, O'Brien KS, Lietman TM, Sie A, Oldenburg CE. Effect of eligibility for referral following mass screening for severe acute malnutrition using mid-upper arm circumference: A prospective regression discontinuity design. PLoS One. 2026 Oct 8;21(10):e0359729. doi: 10.1371/journal.pone.0359729. eCollection 2026.
- Derived from this study: PubMed 41662252Gebreegziabher EA, Sie A, Ouattara M, Bountogo M, Coulibaly B, Boudo V, Ouedraogo T, Lebas E, Hu H, Ante-Testard PA, Gregorich SE, O'Brien KS, Hsiang MS, Glidden DV, Arnold BF, Lietman TM, Oldenburg CE. Exploring heterogeneity in treatment effects: The impact and interaction of asset-based wealth and mass azithromycin distribution on child mortality. PLoS One. 2026 Feb 9;21(2):e0341665. doi: 10.1371/journal.pone.0341665. eCollection 2026.
- Derived from this study: PubMed 41626759Oldenburg CE, Coulibaly B, Sie A, Ouattara M, Bountogo M, Compaore G, Kiemde D, Compaore A, Zonou G, Hinterwirth A, Zhong L, Chen C, Liu Y, Yu D, Abraham T, Lebas E, Hu H, Hilde-Jones M, Arnold BF, Doan T, Lietman TM. Macrolide and Nonmacrolide Resistance After 36 Months of Mass Azithromycin Distribution in Burkina Faso: A Cluster Randomized Trial. Clin Infect Dis. 2026 Jul 8;82(6):946-953. doi: 10.1093/cid/ciag051.
- Derived from this study: PubMed 40779591Bountogo M, Ouattara M, Dah C, Coulibaly B, Ouedraogo T, Zakane A, Boudo V, Lebas E, Hu H, Arnold BF, Lietman TM, Sie A, Oldenburg CE. Azithromycin for infants at risk of poor growth and development: A pooled secondary analysis of two randomized controlled trials. PLoS One. 2025 Aug 8;20(8):e0328208. doi: 10.1371/journal.pone.0328208. eCollection 2025.
- Derived from this study: PubMed 40630579Gebreegziabher EA, Sie A, Ouattara M, Bountogo M, Coulibaly B, Boudo V, Ouedraogo T, Lebas E, Hu H, Ante-Testard PA, Gregorich SE, O'Brien KS, Hsiang MS, Glidden DV, Arnold BF, Lietman TM, Oldenburg CE. Exploring Heterogeneity in Treatment Effects: The Impact and Interaction of Asset-Based Wealth and Mass Azithromycin Distribution on Child Mortality. medRxiv [Preprint]. 2025 Jul 6:2025.07.05.25329685. doi: 10.1101/2025.07.05.25329685.
- Derived from this study: PubMed 40343013Gebreegziabher EA, Ouattara M, Bountogo M, Coulibaly B, Boudo V, Ouedraogo T, Lebas E, Hu H, O'Brien KS, Hsiang MS, Glidden DV, Arnold BF, Lietman TM, Sie A, Oldenburg CE. The role of Seasonal Malaria Chemoprevention in the effect of Azithromycin on Child Mortality: A Secondary Analysis of the CHAT Cluster Randomized Clinical Trial. medRxiv [Preprint]. 2025 May 2:2025.04.30.25326740. doi: 10.1101/2025.04.30.25326740.
- Derived from this study: PubMed 39466816Sie A, Ouattara M, Bountogo M, Boudo V, Ouedraogo T, Dah C, Compaore G, Lebas E, Hu H, Porco TC, Arnold BF, O'Brien KS, Lietman TM, Oldenburg CE. Mass azithromycin for prevention of child mortality among children with acute malnutrition: A subgroup analysis of a cluster randomized controlled trial. PLOS Glob Public Health. 2024 Oct 28;4(10):e0003875. doi: 10.1371/journal.pgph.0003875. eCollection 2024.
- Derived from this study: PubMed 38349371Oldenburg CE, Ouattara M, Bountogo M, Boudo V, Ouedraogo T, Compaore G, Dah C, Zakane A, Coulibaly B, Bagagnan C, Hu H, O'Brien KS, Nyatigo F, Keenan JD, Doan T, Porco TC, Arnold BF, Lebas E, Sie A, Lietman TM. Mass Azithromycin Distribution to Prevent Child Mortality in Burkina Faso: The CHAT Randomized Clinical Trial. JAMA. 2024 Feb 13;331(6):482-490. doi: 10.1001/jama.2023.27393.
- Derived from this study: PubMed 38261579Sie A, Ouattara M, Bountogo M, Dah C, Ouedraogo T, Boudo V, Lebas E, Hu H, Arnold BF, O'Brien KS, Lietman TM, Oldenburg CE. Single-dose azithromycin for infant growth in Burkina Faso: Prespecified secondary anthropometric outcomes from a randomized controlled trial. PLoS Med. 2024 Jan 23;21(1):e1004345. doi: 10.1371/journal.pmed.1004345. eCollection 2024 Jan.
- Derived from this study: PubMed 38231623Sie A, Ouattara M, Bountogo M, Boudo V, Ouedraogo T, Compaore G, Dah C, Bagagnan C, Lebas E, Hu H, Rice J, Porco TC, Arnold BF, Lietman TM, Oldenburg CE. Azithromycin during Routine Well-Infant Visits to Prevent Death. N Engl J Med. 2024 Jan 18;390(3):221-229. doi: 10.1056/NEJMoa2309495.
- Derived from this study: PubMed 31801563Sie A, Ouattara M, Bountogo M, Bagagnan C, Coulibaly B, Boudo V, Lebas E, Brogdon JM, Lin Y, Barnighausen T, Porco TC, Doan T, Lietman TM, Oldenburg CE; Etude CHAT Study Group. A double-masked placebo-controlled trial of azithromycin to prevent child mortality in Burkina Faso, West Africa: Community Health with Azithromycin Trial (CHAT) study protocol. Trials. 2019 Dec 4;20(1):675. doi: 10.1186/s13063-019-3855-9.
- Individual participant dataSharing planned: Yes. De-identified data will be available as per the Bill and Melinda Gates open access policy. Community based data will be available that underline the reported results (texts, tables, figures, and appendices). The study protocol and statistical analysis plan will also be made available. The data will be available following publication in accordance with the BMGF guidelines
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Catherine E Oldenburg, PhD principal investigator
University of California, San Francisco
Tom M Lietman, MD principal investigator
University of California, San Francisco
Ali Sie, MD, PhD principal investigator
Centre de Recherche en Sante de Nouna, Burkina Faso
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Azithromycin in people with Childhood Mortality, run by University of California, San Francisco at 1 site in Burkina Faso.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Burkina Faso. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All-cause Mortality Rate in Children Aged 1-59 Months (time frame: 36 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03676764, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2025.