Comparative Effectiveness of Available Treatments for Sinus and Ear Infections in Children (Acute Otitis Media)

This is a multi-center, randomized, double-blind, placebo-controlled study designed to better understand whether the choice of antibiotic affects symptom burden in children with acute otitis media (AOM). Children enrolled in the study are randomly assigned to receive amoxicillin, amoxicillin-clavulanate, or a matching placebo. Neither the families nor the study team know which treatment a child is receiving during the study period. The primary objective is to compare average daily symptom severity across treatment groups using validated caregiver-reported symptom scales collected through daily electronic diaries. Analyses will account for baseline symptom severity and a combined fever/age category (temperature ≥38.5°C or age <12 months). The goal is to provide rigorous, comparative evidence on antibiotic use in this common pediatric infection to support more informed clinical decision-making and responsible antimicrobial prescribing. The study will also look at whether certain factors such as how sick the child is at the start, presence of fever, age, and how well antibiotics work. The results will help guide better treatment decisions for children with ear infections.

Inclusion criteria

• Age 6 months to <36 months.
• Clinical diagnosis of AOM.

Exclusion criteria

• Known allergy or other contraindication to oral amoxicillin or clavulanate
• Prior use of systemic antibiotics in the last 7 days
• History of renal impairment
• History of hepatic impairment
• Phenylketonuria or allergy to aspartame
• History of craniofacial abnormalities
• Concurrent bacterial infection requiring systemic antibiotic therapy (e.g., pneumonia, streptococcal pharyngitis)
• Ill appearance, systemic toxicity, or immunodeficiency
• Incomplete pneumococcal vaccination, defined as receipt of fewer than three doses of a pneumococcal conjugate vaccine
• Parent or caregiver unable to complete study surveys in English or Spanish
• Previous randomization into either MEASURE trial within the last 6 months
• Mastoiditis
• Conjunctivitis
• Temperature ≥39°C and AOM-SOS score ≥35
• Cochlear implants
• Spontaneous tympanic membrane perforation with otorrhea at presentation (participants who develop perforation and otorrhea after consent remain eligible)