Community Health Azithromycin Trial in Burkina Faso

NCT03676764 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: OPP1187628-A
• Study Type: interventional
• Target: 77,664
• Locations: 1 country
• Sites: 1

Brief 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. 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:

1. 1.Determine the efficacy of biannual mass azithromycin distribution versus placebo in children aged 1-59 months for reduction in all-cause mortality.
2. 2.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.
3. 3.Determine the mechanism behind the effect of biannual mass azithromycin distribution for reduction in child mortality.

Conditions

Childhood Mortality

Keywords

Childhood mortality; Azithromycin; Mass treatment; Vaccine Visit targeted treatment

Outcome Measures

Primary Outcomes (2)

• All-cause Mortality Rate in Children Aged 1-59 Months

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

  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

  6 months

Secondary Outcomes (6)

• Malaria Parasitemia in Children 1-59 Months at 36 Months

  36 months

• Weight-for-height Z-score in Individually Randomized Children at Healthy Child Visits

  6 months

• Height-for-age Z-score in Individually Randomized Children at Healthy Child Visits

  6 months

• Mid-upper Arm Circumference in Individually Randomized Children at Healthy Child Visits

  6 months

• Linear Growth in Individually Randomized Children

  6 months

Study Arms (4)

Biannual mass oral azithromycin

ACTIVE COMPARATOR

Bi-annual Mass Azithromycin distribution to all children 1-60 months old in participating communities

Drug: Azithromycin

Biannual mass oral placebo

PLACEBO COMPARATOR

Bi-annual Mass Placebo distribution to all children 1-60 months old in participating communities

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

Drug: Placebos

Targeted oral azithromycin

ACTIVE COMPARATOR

Targeted azithromycin to children 5 to 12 weeks old at vaccine visit or other healthy child visit

Drug: Azithromycin

Interventions

Azithromycin DRUG

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 azithromycin; Biannual mass oral placebo; Targeted oral azithromycin

Placebos DRUG

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

Biannual mass oral placebo; Targeted oral placebo

Eligibility Criteria

• Age: 1 Month - 59 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• \- Refusal of village chief
• Individuals:
• 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
• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Centre de Recherche en Sante de Nouna, Burkina Faso: collaborator
• Bill and Melinda Gates Foundation: collaborator

Study Sites (1)

Centre de Recherche en Sante de Nouna

Nouna, Burkina Faso

Location

Related Publications (9)

• Oldenburg 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 non-macrolide resistance after 36 months of mass azithromycin distribution in Burkina Faso: A cluster randomized trial. Clin Infect Dis. 2026 Jan 31:ciag051. doi: 10.1093/cid/ciag051. Online ahead of print.

  PMID: 41626759 DERIVED

• Bountogo 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.

  PMID: 40779591 DERIVED

• Gebreegziabher 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.

  PMID: 40630579 DERIVED

• Gebreegziabher 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.

  PMID: 40343013 DERIVED

• Sie 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.

  PMID: 39466816 DERIVED

• Oldenburg 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.

  PMID: 38349371 DERIVED

• Sie 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.

  PMID: 38261579 DERIVED

• Sie 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.

  PMID: 38231623 DERIVED

• Sie 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.

  PMID: 31801563 DERIVED

MeSH Terms

Interventions

Azithromycin

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Thomas Lietman, Director of the UCSF FI Proctor Foundation
• Organization: University of California, San Francisco FI Proctor Foundation

tom.lietman@ucsf.edu

415-476-1442

Study Officials

• Catherine E Oldenburg, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Tom M Lietman, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Ali Sie, MD, PhD

  Centre de Recherche en Sante de Nouna, Burkina Faso

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The trial sites will be masked to outcomes, so the responsibility for monitoring interim analysis will fall on the DSMC
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 17, 2018
• First Posted: September 19, 2018
• Study Start: August 1, 2019
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: February 24, 2025
• Results First Posted: February 24, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: december 2023

Locations

BU (1)