Efficacy of Short-Course Antimicrobial Treatment for Children With Acute Otitis Media and Impact on Resistance
Condition: Acute Otitis Media
MeSH terms: Otitis; Otitis Media
Intervention: Amoxicillin-Clavulanate, 10 days; Amoxicillin-Clavulanate, 5 days
Intervention description: Amoxicillin-clavulanate (90/6.4mg/kg/day in 2 divided doses) Days 1-10; Amoxicillin-clavulanate (90/6.4mg/kg/day in 2 divided doses) Days 1-5
Plus
Placebo Days 6-10
Intervention MeSH terms: Amoxicillin; Clavulanic Acid; Clavulanic Acids; Amoxicillin-Potassium Clavulanate Combination
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 520.0
Sex: All
Minimum age: 6 Months
Maximum age: 23 Months
Healthy volunteers: No
Keywords: acute otitis media; ear infection; antimicrobial therapy; antimicrobial resistance

Summary:

      The investigators will study whether, in young children with acute otitis media (AOM),
      shortening length of antibiotic treatment as a strategy for reducing antimicrobial resistance
      provides satisfactory clinical outcome. This is a Phase 2b multicenter, randomized,
      double-blind, placebo-controlled clinical trial in 600 children aged 6 through 23 months
      comparing the efficacy of consistent reduced-duration antimicrobial treatment (5 days) with
      that of consistent standard-duration treatment (10 days) for each episode of AOM developing
      during a single respiratory season (October 1 through May 31).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Aged 6 through 23 months

          2. Have evidence of AOM defined as:

               -  recent (within 48 hours) onset of signs and symptoms as described in the Acute
                  Otitis Media - Severity of Symptoms (AOM-SOS) Scale AND a score of ≥3 at the time
                  of enrollment on the AOM-SOS scale

               -  middle ear effusion evidenced by the presence of at least 2 of the following:

               -  decreased or absent mobility of the tympanic membrane

               -  yellow or white discoloration of the tympanic membrane

               -  opacification of the tympanic membrane

             AND

               -  acute inflammation evidenced by one of the following:

               -  1+ bulging of the tympanic membrane with either intense erythema or otalgia

               -  2+ or 3+ bulging of the tympanic membrane

          3. Has received at least 2 doses of pneumococcal conjugate vaccine

          4. Parent has provided informed consent

        Exclusion Criteria:

          1. Toxic appearance [capillary refill >3 seconds, systolic blood pressure <60 mm Hg];

          2. Inpatient hospitalization

          3. Clinical or anatomical characteristics that might obscure response to treatment
             (tympanostomy tubes in place, cleft palate, or Down syndrome)

          4. Sensorineural hearing loss (unilateral or bilateral)

          5. Serious underlying systemic problems that might obscure response to infection (cystic
             fibrosis, neoplasm, juvenile diabetes)

          6. Concomitant infection that would preclude evaluation of the response of the child's
             AOM to study product (pneumonia, periorbital cellulitis)

          7. Acute wheezing exacerbation which may require treatment with systemic corticosteroids

          8. Known renal or hepatic dysfunction or insufficiency

          9. History of amoxicillin-clavulanate-associated cholestatic jaundice

         10. Immune dysfunction or receipt of immunosuppressive therapy; chronic gastrointestinal
             conditions (i.e., malabsorption, inflammatory bowel disease)

         11. Co-medications (systemic corticosteroids, more than one dose of systemic antimicrobial
             therapy within 96 hours, receipt of any investigational drug or vaccine within 30
             days)

         12. Hypersensitivity to penicillin, amoxicillin or amoxicillin-clavulanate, or
             phenylketonuria or known hypersensitivity to aspartame

         13. Unable to complete study, or no access to phone

         14. Previously enrolled in this study or currently enrolled in another study