Azithromycin as Adjunctive Treatment for Uncomplicated Severe Acute Malnutrition

• Status: Not yet recruiting
• Trial end date: 2028-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Francisco
• Collaborator: Centre de Recherche en Sante de Nouna, Burkina Faso
• Treatments: Amoxicillin; Azithromycin

Criteria

Children with uncomplicated SAM per Burkina Faso's national guidelines who present to an eligible enrollment site during the study period and meet all of the eligibility criteria below will be considered for enrollment:

Inclusion criteria:

• 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

Exclusion criteria:

• 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.