Neonates and Azithromycin, an Innovation in the Treatment of Children in Burkina Faso

NCT03682653 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: OPP1187628-B
• Study Type: interventional
• Target: 21,832
• Locations: 1 country
• Sites: 1

Brief Summary

Although under-5 mortality rates are declining globally, neonatal mortality remains persistently high in many regions of sub-Saharan Africa. Mass azithromycin distribution to children aged 1-59 months has been shown to reduce childhood mortality in Niger, Tanzania, and Malawi. This study did not evaluate the effect of azithromycin administered during the neonatal period. Observational evidence from high income countries has suggested that macrolides, including erythromycin and azithromycin, may be associated with increased risk of development of infantile hypertrophic pyloric stenosis (IHPS). However, these studies are limited by confounding by indication, as infants only receive antibiotics when they are ill. The investigators proposed an individually randomized trial of azithromycin versus placebo to establish the efficacy and safety of administration of a dose of azithromycin during the neonatal period. The long-term goal is generate evidence that can be used by neonatal and child survival programs related to the use of azithromycin in the youngest children who have the highest risk of mortality. The investigators hypothesize that a single dose of azithromycin administered in the neonatal period will lead to significantly reduced risk of mortality and that this dose will be safe. Objectives

1. 1.Establish the efficacy of a single dose of azithromycin administered during the neonatal period compared to placebo in infants 8 to 27 days of life for reduction in all-cause mortality.
2. 2.Establish the safety of a single dose of azithromycin administered during the neonatal period.

Conditions

Childhood Mortality

Keywords

childhood mortality; neonates; azithromycin; mass drug administration

Outcome Measures

Primary Outcomes (1)

• 6 Month Mortality - All Cause

  The primary outcome of the study was all-cause mortality rate in infants at 6 months of age.

  6 months

Secondary Outcomes (7)

• 12 Month Mortality - All Cause

  12 months

• Vital Status

  12 months

• Change in Weight Over Time

  6 months

• Change in Length Over Time

  6 months

• Proportion of Infants Developing Infantile Hypertrophic Pyloric Stenosis

  8 weeks

Study Arms (2)

Azithromycin

ACTIVE COMPARATOR

a single dose of Azithromycin will be administered to infants between their 8-27th days of life

Drug: Azithromycin

Placebo

PLACEBO COMPARATOR

a single dose of placebo will be administered to infants between their 8-27th days of life

Drug: Placebo

Interventions

Azithromycin DRUG

a single dose of Azithromycin will be administered to infants between their 8-27th days of life

Azithromycin

Placebo DRUG

a single dose of Placebo will be administered to infants between their 8-27th days of life

Placebo

Eligibility Criteria

• Age: 8 Days - 27 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Within 4 hours of a facility that can provide services for pyloromyotomy (Ouagadougou or Bobo Dioulasso)
• Accessible during the rainy season
• Ultrasound machine available OR a facility in which an ultrasound machine could be placed is within 1 hour

You may not qualify if:

• Refusal of village chief
• Individuals:
• Weight over 2500 g
• Able to feed orally
• Family intends to stay in study area for at least 6 months
• Appropriate consent from at least one caregiver
• No known allergy to azalides
• Not living within one of the communities included in the community study(CHAT/CHATON)
• No hepatic failure manifested by neonatal jaundice
• Weight \<2500 g
• Unable to feed orally
• Family planning to move
• Mother/caregiver not willing to participate
• Allergic to azalides
• Living in one of the communities included in the community study (CHAT/CHATON)

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 Santé de Nouna

Nouna, BP 02, Burkina Faso

Location

Related Publications (5)

• Bountogo M, Sie A, Zakane A, Compaore G, Ouedraogo T, Brogdon J, Lebas E, Nyatigo F, Medvedev MM, Arnold BF, Lietman TM, Oldenburg CE; NAITRE Study Team. Infant mortality and growth failure after oral azithromycin among low birthweight and underweight neonates: A subgroup analysis of a randomized controlled trial. PLOS Glob Public Health. 2023 May 15;3(5):e0001009. doi: 10.1371/journal.pgph.0001009. eCollection 2023.

  PMID: 37186577 DERIVED

• Sie A, Bountogo M, Zakane A, Compaore G, Ouedraogo T, Ouattara M, Lebas E, Brogdon J, Nyatigo F, O'Brien KS, Porco TC, Barnighausen T, Arnold BF, Lietman TM, Oldenburg CE; NAITRE Study Team. Neonatal Azithromycin Administration and Growth during Infancy: A Randomized Controlled Trial. Am J Trop Med Hyg. 2023 Mar 27;108(5):1063-1070. doi: 10.4269/ajtmh.22-0763. Print 2023 May 3.

  PMID: 36972694 DERIVED

• Oldenburg CE, Sie A, Bountogo M, Zakane A, Compaore G, Ouedraogo T, Koueta F, Lebas E, Brogdon J, Nyatigo F, Doan T, Porco TC, Arnold BF, Lietman TM; NAITRE Study Team. Neonatal azithromycin administration for prevention of infant mortality. NEJM Evid. 2022 Apr;1(4):EVIDoa2100054. doi: 10.1056/EVIDoa2100054. Epub 2022 Mar 17.

  PMID: 35692260 DERIVED

• Bountogo M, Sie A, Zakane A, Compaore G, Ouedraogo T, Lebas E, Brogdon J, Nyatigo F, Arnold BF, Lietman TM, Oldenburg CE. Antenatal care attendance and risk of low birthweight in Burkina Faso: a cross-sectional study. BMC Pregnancy Childbirth. 2021 Dec 13;21(1):825. doi: 10.1186/s12884-021-04310-6.

  PMID: 34903190 DERIVED

• Sie A, Bountogo M, Nebie E, Ouattara M, Coulibaly B, Bagagnan C, Zabre P, Lebas E, Brogdon J, Godwin WW, Lin Y, Porco T, Doan T, Lietman TM, Oldenburg CE; NAITRE Study Group. Neonatal azithromycin administration to prevent infant mortality: study protocol for a randomised controlled trial. BMJ Open. 2019 Sep 4;9(9):e031162. doi: 10.1136/bmjopen-2019-031162.

  PMID: 31488494 DERIVED

MeSH Terms

Interventions

Azithromycin

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Thomas Lietman
• Organization: UCSF FI Proctor

tom.lietman@ucsf.edu

(414) 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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: individually randomized trial of azithromycin versus placebo to establish the efficacy and safety of administration of a dose of azithromycin during the neonatal period

Study Record Dates

• First Submitted: September 19, 2018
• First Posted: September 24, 2018
• Study Start: April 11, 2019
• Primary Completion: May 1, 2022
• Study Completion: December 31, 2022
• Last Updated: June 27, 2023
• Results First Posted: June 27, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The data will be available following publication, without any embargo period.

Locations

BU (1)