Azithromycin as Adjunctive Treatment for Uncomplicated Severe Acute Malnutrition: the AMOUR Trial

Status: Recruiting
Location: See location...
Intervention Type: Other, Drug
Study Type: Interventional
Study Phase: Phase 4
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 6 months
Maximum Age: 4
Healthy Volunteers: f
View:

• 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

Locations
Other Locations
Burkina Faso
Centre de recherche en Santé de nouna
RECRUITING
Nouna
Contact Information
Primary
Catherine Oldenburg, ScD
catherine.oldenburg@ucsf.edu
4154761442
Backup
Elodie Lebas, RN
elodie.lebas@ucsf.edu
4154761442
Time Frame
Start Date: 2024-10-23
Estimated Completion Date: 2028-12-29
Participants
Target number of participants: 3000
Treatments
Experimental: Azithromycin
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).
Active_comparator: Amoxicillin
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).
Placebo_comparator: Placebo
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).
Related Therapeutic Areas
Sponsors
Leads: University of California, San Francisco
Collaborators: Centre de Recherche en Sante de Nouna, Burkina Faso, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

This content was sourced from clinicaltrials.gov