AOM Therapy Trial in Young Children

Condition(s) targeted: Acute Otitis Media

Intervention: Amoxicillin-clavulanate (Drug); Placebo (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Overall contact:
Alejandro Hoberman, Phone: (412) 692-5249

The purpose of this study is to learn whether or not all children with ear infections (acute otitis media or AOM) should be treated with antibiotics. The study will compare two treatment strategies, "watchful waiting" or treatment with antibiotics, to determine which is more appropriate for children with AOM. About 268 children in Pittsburgh, between the ages of 6-23 months, with AOM will be enrolled in the study. They will be treated either with Augmentin (an antibiotic) or placebo for 10 days and closely followed for about 1 month. Parents will be asked to write information about their child in a Patient Diary. A general physical exam, including an ear exam, will be performed 4 times during the study. A mucus sample will be collected from the back of each child's nose. Parents will be asked questions during phone calls and at every visit. If a child has not improved or has worsened, the investigators will prescribe a different antibiotic that is known to kill resistant germs.

Official title: Efficacy of Antimicrobials in Young Children With Acute Otitis Media (AOM)

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome:

Compare time to resolution of symptoms in children receiving amoxicillin-clavulanate to children receiving placebo.

Safety: occurrence of protocol defined diarrhea (3 or more watery stools in 1 day or 2 watery stools per day for 2 consecutive days).

Secondary outcome:

Compare the 2 treatment groups regarding the quantity of analgesic medication administered by children's parents.

Compare effects of amoxicillin-clavulanate vs. placebo on overall proportion of children with nasopharyngeal (NP) colonization with AOM pathogens and on the proportion of children with NP colonization with penicillin non-susceptible S. pneumoniae.

Compare parental satisfaction with therapy between the 2 treatment groups.

Compare direct and indirect medical costs between the 2 treatment groups.

Compare the 2 treatment groups regarding tympanometric outcomes using an algorithm that permits estimation of the probability of middle ear effusion given any particular tympanographic configuration.

Compare the incidence of adverse events accompanying the 2 treatment regimens.

Compare the proportion of children in each treatment group who develop worsening symptoms.

Evaluate clinical efficacy of amoxicillin-clavulanate vs. placebo at the on-therapy visit.

Evaluate clinical efficacy of amoxicillin-clavulanate vs. placebo at the end of therapy.

Compare the symptom burden between treatment groups.

Detailed description: The purpose of this randomized, double-masked, placebo-controlled, single-center clinical trial is to determine the efficacy of antimicrobials in young children with acute otitis media (AOM). The primary objective is to compare time to resolution of symptoms in children receiving amoxicillin-clavulanate (90/6. 4mg/kg/day in 2 divided doses for 10 days) to children receiving placebo (in 2 divided doses for 10 days). The secondary objectives are to: evaluate the clinical efficacy of amoxicillin-clavulanate vs. placebo at the on-therapy visit (Day 4-5, and at least 72 hours after initial dose of study medication); evaluate the clinical efficacy of amoxicillin-clavulanate vs. placebo at the end-of-therapy (Day 10-12); compare symptom burden (as assessed by the AOM-Severity of Symptoms [AOM-SOS] and AOM-Faces scales) between treatment groups during each of the first 7 days of therapy and at all study visits; compare the proportion of children in each treatment group who develop worsening symptoms before having received 72 hours of study medication; compare the two treatment groups regarding the quantity of analgesic medication administered by children's parents; compare the incidence of adverse events accompanying the two treatment regimens; compare the effects of amoxicillin-clavulanate vs. placebo on the overall proportion of children with nasopharyngeal (NP) colonization with AOM pathogens (S. pneumoniae, H. influenzae, M. catarrhalis, S. pyogenes), and on the proportion of children with NP colonization with penicillin non-susceptible S. pneumoniae; compare the 2 treatment groups regarding tympanometric outcomes at the on-therapy (Day 4-5), end-of-therapy (Day 10-12) and follow-up (Day 21-25) visits, using an algorithm that permits estimation of the probability of middle ear effusion given any particular tympanographic configuration; compare direct and indirect medical costs between the two treatment groups; and compare parental satisfaction with therapy between the two treatment groups. Participants will include 268 children, aged 6 to 23 months, diagnosed with acute otitis media in Western Pennsylvania. These participants will be recruited into the study at Children's Hospital of Pittsburgh (CHP), Pittsburgh, PA, and Armstrong Pediatrics (Children's Community Pediatrics: an affiliate of CHP) in Kittanning, PA. Subjects will be randomized to receive either Augmentin or placebo twice daily for 10 days. Parents of the subject will be asked to track symptom status, medication use (study medication and acetaminophen), fever and diarrhea in a study memory aid. Study procedures will include a medical history, vital signs, weight, clinical information regarding signs and symptoms of infection, nasopharyngeal specimens, and a physical exam including a tympanometry. Each child will be examined three additional times: 4-5 days after starting the medicine, study day 10-12 and 21-25 days after enrolling in the study. During these visits, study staff will review the child's symptoms and examine the child's ears. The study staff will also obtain a nasopharyngeal culture in order to look for resistant bacteria and to make appropriate changes in antibiotic treatment. Daily telephone assessments will be made by study staff on days 2, 3, and 4 of therapy to make sure the child is getting better. The study staff will see a child anytime a parent feels their child has not improved or has worsened. The primary outcome of the study is the time to resolution of symptoms where resolution is determined based on AOM-SOS scores.

Minimum age: 6 Months. Maximum age: 23 Months. Gender(s): Both.

Criteria:

Inclusion Criteria:

- aged 6 to 23 months

- have received at least two doses of pneumococcal conjugate vaccine (Prevnar) and

Haemophilus influenzae type B vaccine

- have evidence of acute otitis media (AOM) defined as: Recent (within 48 hours), onset

of signs and symptoms and a score of greater than or equal to 3 on the AOM-SOS scale.

Middle ear effusion evidenced by at least two of the following:

- decreased or absent tympanic membrane mobility by pneumatic otoscopy,

- yellow or white discoloration of the tympanic membrane,

- opacification of the tympanic membrane, plus

- 1+ bulging of the tympanic membrane with either marked erythema or otalgia, or

- 2+ or 3+ bulging of the tympanic membrane

Exclusion Criteria:

- certain signs or symptoms (e. g., toxic appearance [capillary refill greater than 3

seconds, systolic blood pressure less than 60 mm Hg], otalgia for a period greater than 48 hours, spontaneous perforation of the tympanic membrane and drainage or temperature greater than or equal to 105 degrees F);

- clinical or anatomical characteristics that might obscure response to treatment (e. g.,

tympanostomy tube[s] in place or a history of tympanostomy tubes, unrepaired or repaired overt or submucous cleft palate, high-arched palate, or Down's syndrome);

- underlying systemic problems that might obscure response to infection (e. g., serious

underlying disease [e. g., cystic fibrosis, neoplasm, juvenile diabetes]), concomitant infection that would preclude evaluation of the response of the child's AOM to study medication, known renal insufficiency (i. e., serum creatinine greater than or equal to 1. 5 times upper limit of normal for age), known hepatic insufficiency or a history of amoxicillin-clavulanate-associated cholestatic jaundice or hepatic dysfunction, history of immune dysfunction, deficiency or receipt of immunosuppressive therapy, chronic gastrointestinal conditions (i. e., malabsorption, inflammatory bowel disease), malignancy;

- sensorineural hearing loss either unilateral or bilateral;

- comedications (e. g., systemic corticosteroids at any point while enrolled in the

study, more than one dose of systemic antimicrobial therapy within 96, any investigational drug or vaccine;

- hypersensitivity to penicillin, amoxicillin or amoxicillin-clavulanate, or

phenylketonuria or known hypersensitivity to aspartame;

- unable to complete the study protocol or not having access to a telephone; and

- current enrollment in another study or previously enrolled in this study.

Alejandro Hoberman, Phone: (412) 692-5249

Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States; Recruiting

Starting date: November 2006
Ending date: March 2009
Last updated: February 12, 2009