Azithromycin as Adjunctive Treatment for Uncomplicated Severe Acute Malnutrition

NCT06010719 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 23-394115R01HD111532
• Study Type: interventional
• Target: 3,000
• Locations: 1 country
• Sites: 1

Brief Summary

Amoxicillin is recommended by the World Health Organization (WHO) as adjunctive therapy for the treatment of uncomplicated severe acute malnutrition (SAM). Because children with uncomplicated SAM may have asymptomatic infection due to immune suppression, presumptive treatment with a broad-spectrum antibiotic may be beneficial by clearing any existing infection and improving outcomes. Two randomized placebo-controlled randomized trials have evaluated amoxicillin for uncomplicated SAM and have found conflicting results. These results may indicate either that antibiotics are not helpful for the management of uncomplicated SAM, or that a better antibiotic is needed. Recently, the investigators demonstrated that biannual mass azithromycin distribution as a single oral dose reduces all-cause child mortality in sub-Saharan Africa. Children with uncomplicated SAM, who have an elevated risk of mortality relative to their well-nourished peers, may particularly benefit from presumptive azithromycin treatment. Our pilot data demonstrated feasibility in rapid enrollment of children with uncomplicated SAM in our study area, and showed no significant difference between azithromycin and amoxicillin, demonstrating equipoise for a full-scale trial. Here, the investigators propose an individually randomized trial in which children will be randomized to a) azithromycin, b) amoxicillin, or c) placebo, and evaluated for differences in weight gain, nutritional recovery, and the gut microbiome. The results of this study will strengthen the evidence base for policy related to the use of antibiotics as part of the management of uncomplicated SAM, including additional evidence of amoxicillin versus placebo as well as evaluation of an antibiotic class that has not been considered for uncomplicated SAM, which may lead to changes in guidelines for treatment.

Conditions

Malnutrition, Child; Severe Acute Malnutrition

Outcome Measures

Primary Outcomes (1)

• Weight Gain

  This will be measured as weight gain in g/kg/day at 8 weeks from enrollment.

  8 weeks

Secondary Outcomes (3)

• Time for Nutritional recovery

  12 weeks

• Number of Transfer to inpatient care

  12 weeks

• Mortality

  12 months

Study Arms (3)

Azithromycin

EXPERIMENTAL

Children enrolled in the trial will be randomized to either the azithromycin, amoxicillin, or placebo arm. Children randomized to the azithromycin arm will receive all standard severe acute malnutrition (SAM) outpatient treatment per Burkinabe national guidelines, except that the standard amoxicillin treatment will be changed to azithromycin. Children will receive a directly observed dose of azithromycin (20 mg/kg, single directly observed dose, oral suspension), followed by a 7-day course of placebo (administered at 80 mg/kg, split into 2 daily doses for 7 days, oral suspension).

Drug: Azithromycin

Amoxicillin

ACTIVE COMPARATOR

Children enrolled in the trial will be randomized to either the azithromycin, amoxicillin, or placebo arm. Children randomized to the amoxicillin arm will receive all standard severe acute malnutrition (SAM) outpatient treatment per Burkinabe national guidelines, including a 7-day course of amoxicillin (administered at 80 mg/kg, split into 2 daily doses for 7 days, oral suspension).

Drug: Amoxicillin

Placebo

PLACEBO COMPARATOR

Children enrolled in the trial will be randomized to either the azithromycin, amoxicillin, or placebo arm. Children randomized to the placebo arm will receive all standard severe acute malnutrition (SAM) outpatient treatment per Burkinabe national guidelines, except that the the standard amoxicillin treatment will be changed to placebo (administered at 80 mg/kg, split into 2 daily doses for 7 days, oral suspension).

Other: Placebo

Interventions

Azithromycin DRUG

oral azithromycin (20 mg/kg, single directly observed dose, oral suspension),

Azithromycin

Amoxicillin DRUG

Standard of Care. A 7-day, twice-daily course of amoxicillin will be offered as a syrup to children (80 mg/kg divided into twice-daily doses, estimated with weight-based dosing).

Amoxicillin

Placebo OTHER

A 7-day, twice-daily course of placebo will be offered as a syrup to children (80 mg/kg divided into twice-daily doses, estimated with weight-based dosing).

Placebo

Eligibility Criteria

• Age: 6 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 6-59 months
• WHZ\<-3 SD or MUAC\<115 mm
• Primary residence within a catchment area of an enrollment site
• Available for full 8-week study (primary endpoint)
• Not admitted to a nutritional program for SAM treatment in the previous 2 weeks
• No edema
• No antibiotic use in the past 7 days
• No clinical complications requiring antibiotic or inpatient treatment\*\*
• No congenital abnormality or chronic debilitating illness that would lead to predictable growth faltering or reduce likelihood of SAM treatment benefit (such as cerebral palsy, Down syndrome, congenital heart disease, cleft lip/palate, etc)
• No known allergies to macrolides/azalides or amoxicillin/penicillin
• Sufficient appetite according to a feeding test with RUTF
• Written informed consent from at least one parent or guardian

You may not qualify if:

• Age less than 6 month or more than 59 months
• WHZ\>-3 SD or MUAC\>115 mm
• Primary residence is not within a catchment area of an enrollment site
• Not Available for full 8-week study (primary endpoint)
• Admitted to a nutritional program for SAM treatment in the previous 2 weeks
• Edema
• Antibiotic use in the past 7 days
• Clinical complications requiring antibiotic or inpatient treatment\*\*
• Congenital abnormality or chronic debilitating illness that would lead to predictable growth faltering or reduce likelihood of SAM treatment benefit (such as cerebral palsy, Down syndrome, congenital heart disease, cleft lip/palate, etc)
• Known allergies to macrolides/azalides or amoxicillin/penicillin
• No Sufficient appetite according to a feeding test with RUTF
• No Written informed consent from at least one parent or guardian
• Per Burkinabé guidelines, children any of the following conditions will not be eligible for the trial and will be referred to an inpatient facility: MUAC \<115 mm with complications; MUAC \<115 mm plus edema; bipedal pitting edema; anorexia or no appetite for RUTF; diarrhea and dehydration; unable to ingest anything without vomiting; severe pneumonia; open cutaneous lesions; hypothermia (35\*C); fever (38.5\*C); paleness suggesting severe anemia; hypoglycemia; very weak, lethargic, or unconscious; convulsions; signs of vitamin A deficiency; or a condition requiring IV infusion or an NG tube.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Centre de Recherche en Sante de Nouna, Burkina Faso: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Centre de recherche en Santé de nouna

Nouna, Kossi, Burkina Faso

RECRUITING

Related Publications (2)

• Oldenburg CE, Sie A, Coulibaly B, Ouermi L, Dah C, Tapsoba C, Barnighausen T, Ray KJ, Zhong L, Cummings S, Lebas E, Lietman TM, Keenan JD, Doan T. Effect of Commonly Used Pediatric Antibiotics on Gut Microbial Diversity in Preschool Children in Burkina Faso: A Randomized Clinical Trial. Open Forum Infect Dis. 2018 Nov 2;5(11):ofy289. doi: 10.1093/ofid/ofy289. eCollection 2018 Nov.

  PMID: 30515431 BACKGROUND

• Bountogo M, Zakane A, Ouedraogo TA, Ouermi L, Compaore G, Compaore A, Coulibaly B, Koueta F, Burroughs HR, Fetterman I, La Mons JL, Lebas E, Doan T, Hsiang M, O'Brien KS, Arnold B, Sie A, Oldenburg CE. Azithromycin as adjunctive treatment for uncomplicated severe acute malnutrition (AMOUR): study protocol for a double-masked randomised controlled trial. BMJ Open. 2025 Jul 1;15(7):e104591. doi: 10.1136/bmjopen-2025-104591.

  PMID: 40592757 DERIVED

MeSH Terms

Conditions

Child Nutrition Disorders; Severe Acute Malnutrition

Interventions

Azithromycin; Amoxicillin

Condition Hierarchy (Ancestors)

Nutrition Disorders; Nutritional and Metabolic Diseases; Malnutrition

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Catherine Oldenburg, ScD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Catherine Oldenburg, ScD

CONTACT

4154761442; catherine.oldenburg@ucsf.edu

Elodie Lebas, RN

CONTACT

4154761442; elodie.lebas@ucsf.edu

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: SPONSOR

Study Record Dates

• First Submitted: August 18, 2023
• First Posted: August 25, 2023
• Study Start: October 23, 2024
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 29, 2028
• Last Updated: October 15, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1)