Azithromycin to Prevent Post-discharge Morbidity and Mortality in Kenyan Children

NCT02414399 | Unknown Phase 4 Results DMC FDA Drug

• 2 other identifiers: STUDY00002592R01HD079695
• Study Type: interventional
• Target: 1,400
• Locations: 1 country
• Sites: 1

Brief Summary

Children hospitalized with severe illness in sub-Saharan Africa are at high risk of morbidity and mortality following discharge from hospital. These children represent an accessible high-risk population in which targeted interventions to prevent morbidity and mortality could have dramatic impact. A large cluster randomized trial of azithromycin delivered in a mass drug administration program within trachoma endemic areas in sub-Saharan Africa demonstrated an almost 50% mortality benefit in children 1-9 years of age in treated communities. However, mass drug administration of azithromycin leads to the rapid emergence of macrolide resistance within treated communities and is expensive. The targeted delivery of azithromycin to children at hospital discharge may be a novel and practical intervention to maximize benefit while minimizing risk of antibiotic resistance. This is a randomized, double-blind, placebo-controlled trial to determine the efficacy of azithromycin provided at discharge, compared to placebo, in reducing mortality and re-hospitalization rates in children age 1-59 months in Kenya. The study will also investigate potential mechanisms by which azithromycin may reduce morbidity and mortality in this population and will assess the emergence of antibiotic resistance among treated individuals and their primary caregivers. A cost-effectiveness analysis of the intervention will also be conducted.

Conditions

Pneumonia; Diarrhea; Malaria; Co-infection; Death; Malnutrition

Keywords

post-discharge mortality; morbidity and mortality prevention; azithromycin; linear growth

Outcome Measures

Primary Outcomes (1)

• Re-hospitalization or Death

  Incidence rate of a composite outcome of mortality and hospital readmission during the 6 month post-discharge (follow-up) period.

  6 months

Secondary Outcomes (9)

• Mean Change in Length for Age Z-score (LAZ) Between Baseline and Outcome Assessment

  6 months

• The Number of Children With Diarrhea Re-hospitalizations Following Randomization

  6 months

• The Number of Children With Acute Respiratory Illness Re-hospitalizations Following Randomization

  6 months

• The Number of Children With Malnutrition Re-hospitalizations Following Randomization

  6 months

• The Number of Children With Malaria Re-hospitalizations Following Randomization

  6 months

Study Arms (2)

Azithromycin

EXPERIMENTAL

Azithromycin 10mg/kg for one day, then 5mg/kg for four days, a total of five days of experimental treatment.

Drug: Azithromycin

Placebo

PLACEBO COMPARATOR

5 days of taste/appearance/bottle-matched placebo

Drug: Placebo

Interventions

Azithromycin DRUG

oral administration of Azithromycin

Also known as: Zithromax, Zmax

Azithromycin

Placebo DRUG

5 days of taste/appearance/bottle-matched inactive substance

Placebo

Eligibility Criteria

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

You may qualify if:

• Age 1-59 months,
• Plan to remain in study area greater than 6 months
• Discharged from hospital following non-trauma related admission

You may not qualify if:

• Contraindication to azithromycin use and other prophylactic antibiotic use

Sponsors & Collaborators

• University of Washington: lead
• Kenya Medical Research Institute: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Kisii Teaching and Referral Hospital, Homa Bay District Hospital, St. Paul's Mission Hospital

Kisii and Homa Bay Counties, Kenya

Location

Related Publications (18)

• Porco TC, Gebre T, Ayele B, House J, Keenan J, Zhou Z, Hong KC, Stoller N, Ray KJ, Emerson P, Gaynor BD, Lietman TM. Effect of mass distribution of azithromycin for trachoma control on overall mortality in Ethiopian children: a randomized trial. JAMA. 2009 Sep 2;302(9):962-8. doi: 10.1001/jama.2009.1266.

  PMID: 19724043 BACKGROUND

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• Keenan JD, Ayele B, Gebre T, Zerihun M, Zhou Z, House JI, Gaynor BD, Porco TC, Emerson PM, Lietman TM. Childhood mortality in a cohort treated with mass azithromycin for trachoma. Clin Infect Dis. 2011 Apr 1;52(7):883-8. doi: 10.1093/cid/cir069.

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• Roy SK, Chowdhury AK, Rahaman MM. Excess mortality among children discharged from hospital after treatment for diarrhoea in rural Bangladesh. Br Med J (Clin Res Ed). 1983 Oct 15;287(6399):1097-9. doi: 10.1136/bmj.287.6399.1097.

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• Wiens MO, Pawluk S, Kissoon N, Kumbakumba E, Ansermino JM, Singer J, Ndamira A, Larson C. Pediatric post-discharge mortality in resource poor countries: a systematic review. PLoS One. 2013 Jun 25;8(6):e66698. doi: 10.1371/journal.pone.0066698. Print 2013.

  PMID: 23825556 BACKGROUND

• Berkley JA, Bejon P, Mwangi T, Gwer S, Maitland K, Williams TN, Mohammed S, Osier F, Kinyanjui S, Fegan G, Lowe BS, English M, Peshu N, Marsh K, Newton CR. HIV infection, malnutrition, and invasive bacterial infection among children with severe malaria. Clin Infect Dis. 2009 Aug 1;49(3):336-43. doi: 10.1086/600299.

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  PMID: 1548821 BACKGROUND

• Pavlinac PB, Singa BO, John-Stewart GC, Richardson BA, Brander RL, McGrath CJ, Tickell KD, Amondi M, Rwigi D, Babigumira JB, Kariuki S, Nduati R, Walson JL. Azithromycin to prevent post-discharge morbidity and mortality in Kenyan children: a protocol for a randomised, double-blind, placebo-controlled trial (the Toto Bora trial). BMJ Open. 2017 Dec 29;7(12):e019170. doi: 10.1136/bmjopen-2017-019170.

  PMID: 29289941 BACKGROUND

• Libby TE, Karani A, Tickell KD, Akech D, Singa B, Rwigi D, Kariuki K, Onamu N, Ounga D, Berkley JA, Walson JL, Scott JAG, Pavlinac PB. The effect of a 5-day course of azithromycin on Streptococcus pneumoniae carriage and antimicrobial resistance among Kenyan children discharged from hospital. J Infect Dis. 2026 Jan 16:jiag028. doi: 10.1093/infdis/jiag028. Online ahead of print.

  PMID: 41542944 DERIVED

• Atlas HE, Mogeni P, Shawon RA, Tickell KD, Bunyige L, Monchari I, Oongo S, Diakhate MM, Brander RL, Liru M, Bogonko G, Nduati R, Richardson BA, John-Stewart G, Walson JL, Singa BO, Pavlinac PB, McGrath CJ. Effect of azithromycin on post-discharge growth in Kenyan children. BMJ Glob Health. 2025 Nov 23;10(11):e020294. doi: 10.1136/bmjgh-2025-020294.

  PMID: 41285436 DERIVED

• Mogeni P, Ochieng JB, Atlas HE, Tickell KD, Rwigi D, Kariuki K, Aluoch LR, Sonye C, Apondi E, Ambila L, Diakhate MM, Singa BO, Liu J, Platts-Mills JA, Fang FC, Walson JL, Houpt ER, Pavlinac PB. Impact of Macrolide Resistance on Azithromycin for Prevention of Rehospitalization or Death Among Children Discharged From Hospitals in Western Kenya. J Infect Dis. 2025 Aug 14;232(2):e301-e308. doi: 10.1093/infdis/jiaf208.

  PMID: 40257829 DERIVED

• Pavlinac PB, Singa B, Huang ML, Shrestha L, Li V, Atlas HE, Diakhate MM, Brander R, Meshak L, Bogonko G, Tickell KD, McGrath CJ, Machuara IM, Ounga DO, Berkley JA, Richardson BA, John-Stewart G, Walson JL, Slyker J. Cytomegalovirus Viremia Predicts Postdischarge Mortality in Kenyan HIV-Exposed Uninfected Children. J Infect Dis. 2022 Nov 1;226(9):1519-1527. doi: 10.1093/infdis/jiac047.

  PMID: 35152295 DERIVED

• Pavlinac PB, Singa BO, Tickell KD, Brander RL, McGrath CJ, Amondi M, Otieno J, Akinyi E, Rwigi D, Carreon JD, Tornberg-Belanger SN, Nduati R, Babigumira JB, Meshak L, Bogonko G, Kariuki S, Richardson BA, John-Stewart GC, Walson JL. Azithromycin for the prevention of rehospitalisation and death among Kenyan children being discharged from hospital: a double-blind, placebo-controlled, randomised controlled trial. Lancet Glob Health. 2021 Nov;9(11):e1569-e1578. doi: 10.1016/S2214-109X(21)00347-8. Epub 2021 Sep 21.

  PMID: 34559992 DERIVED

MeSH Terms

Conditions

Pneumonia; Diarrhea; Malaria; Coinfection; Death; Malnutrition

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Protozoan Infections; Parasitic Diseases; Mosquito-Borne Diseases; Vector Borne Diseases; Pathologic Processes; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Patricia Pavlinac
• Organization: University of Washington

ppav@uw.edu

206 616-8326

Study Officials

• Judd L Walson, MD, MPH

  University of Washington Department of Global Health

  PRINCIPAL INVESTIGATOR

• Patricia B Pavlinac, PhD, MS

  University of Washington Department of Global Health

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 31, 2015
• First Posted: April 10, 2015
• Study Start: June 28, 2016
• Primary Completion: May 4, 2020
• Study Completion: December 28, 2025
• Last Updated: December 4, 2023
• Results First Posted: December 4, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: With publication of primary manuscript (Sep 2021)
• Access Criteria: Open Access

Locations

KE (1)