Clinical trial NCT00377260: Acute Otitis Media (AOM) Therapy Trial in Young Children
Official title: Efficacy of Antimicrobials in Young Children With Acute Otitis Media (AOM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Otitis Media
Keywords: acute otitis media, infants, children
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2006-09-18
Enrollment: 291
Sex: ALL
Minimum age (years): 6
Maximum age (years): 23
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 objectives are to compare time to resolution of symptoms (initial and sustained) 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), and to compare the weighted average AOM-Severity of Symptoms (AOM-SOS) scores in the two groups during days 1-7. 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 visit (Day 10-12); compare 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 amoxicillin-clavulanate 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 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.

Eligibility 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:

  1. Recent (within 48 hours), onset of signs and symptoms and a score of greater than or equal to 3 on the AOM-SOS scale.
  2. 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.

Primary outcomes:
measure: The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1, According to Treatment Assignment
timeFrame: The first 7 days on therapy
measure: The Time to Resolution of Symptoms, Defined as Acute Otitis Media-Severity of Symptoms (AOM-SOS) Score of 0 or 1 on Two Consecutive Occasions, According to Treatment Assignment
timeFrame: The first 7 days on therapy
measure: The Weighted Average Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, According to Treatment Assignment
timeFrame: During the first 7 days of therapy
Secondary outcomes:
measure: The Distribution of Clinical Failures by the On-therapy Visit According to Treatment Assignment
timeFrame: On-therapy visit. The mean day for this visit was 5.0.
measure: The Distribution of Clinical Failures by the End-of-therapy Visit According to Treatment Assignment
timeFrame: End-of-therapy visit. The mean day for this visit was 11.6.
measure: The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment
timeFrame: During the first 7 days of therapy
measure: The Distribution of Children Developing Worsening Symptoms Prior to Receiving 72 Hours of Study Medication According to Treatment Assignment
timeFrame: Before receiving 72 hours of study medication
measure: The Mean Number of Times Analgesic Medication Was Administered to the Child According to Treatment Assignment
timeFrame: The first 10 days of follow-up
measure: The Distribution of Children With Observed or Parent Reported Adverse Events or Complications According to Treatment Assignment
timeFrame: We monitored children and queried parents regarding adverse events at each study visit, i.e. Day 4-5, Day 10-12, and Day 21-25, and at interim visits. The last assessment was made at the Day 21-25 visit. The mean day for this visit was 22.8.
measure: The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the End-of-therapy Visit According to Treatment Assignment
timeFrame: End-of-therapy visit. The mean day for this visit was 11.6.
measure: The Distribution of Children With Nasopharyngeal (NP) Colonization With Penicillin-susceptible Streptococcus Pneumoniae (S. pn) at the End-of-therapy Visit According to Treatment Assignment
timeFrame: End-of-therapy visit. The mean day for this visit was 11.6.
measure: The Distribution of Children With Nasopharyngeal (NP) Colonization With AOM Pathogens at the Follow-up Visit According to Treatment Assignment
timeFrame: Follow-up visit. The mean day for this visit was 22.8.
measure: The Distribution of Children With Nasopharyngeal (NP) Colonization With Penicillin-susceptible Streptococcus Pneumoniae (S. pn) at the Follow-up Visit
timeFrame: Follow-up visit. The mean day for this visit was 22.8.
measure: The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the On-therapy Visit According to Treatment Assignment
timeFrame: On-therapy visit. The mean day for this visit was 5.0.
measure: The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the End-of-therapy Visit According to Treatment Assignment
timeFrame: End-of-therapy visit. The mean day for this visit was 11.6.
measure: The Probability of Middle Ear Effusion, Based on an Algorithm That Estimates the Probability of Middle Ear Effusion From an Interpretable Tympanographic Configuration, at the Follow-up Visit According to Treatment Assignment
timeFrame: Follow-up visit. The mean day for this visit was 22.8.
measure: The Mean Number of Visits to a Primary Care Provider (PCP) According to Treatment Assignment
timeFrame: This was assessed at each study visit, i.e. Day 4-5, Day 10-12, Day 21-25, and at interim visits. The last assessment was made at the Day 21-25 visit. The mean day for this latter visit was 22.8.
measure: The Mean Number of Emergency Room Visits According to Treatment Assignment
timeFrame: This was assessed at each study visit, i.e. Day 4-5, Day 10-12, Day 21-25, and at interim visits. The last assessment was made at the Day 21-25 visit. The mean day for this latter visit was 22.8.
measure: The Mean Number of Antibiotic Prescriptions, Exclusive of Study Medication, According to Treatment Assignment
timeFrame: This was assessed at each study visit, i.e. Day 4-5, Day 10-12, Day 21-25, and at interim visits. The last assessment was made at the Day 21-25 visit. The mean day for this latter visit was 22.8.
measure: The Total Number of Visits, Summed Across All Participants, at Which a Family Member Reported Having Missed Work According to Treatment Assignment
timeFrame: This was assessed at each study visit, i.e. Day 4-5, Day 10-12, Day 21-25, and at interim visits. The last assessment was made at the Day 21-25 visit. The mean day for this latter visit was 22.8.
measure: The Total Number of Visits, Summed Across All Participants, at Which a Family Member Reported Making Special Daycare Arrangements According to Treatment Assignment
timeFrame: This was assessed at each study visit, i.e. Day 4-5, Day 10-12, Day 21-25, and at interim visits. The last assessment was made at the Day 21-25 visit. The mean day for this latter visit was 22.8.
measure: The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the On-therapy Visit According to Treatment Assignment
timeFrame: On-therapy visit. The mean day for this visit was 5.0.
measure: The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the End-of-therapy Visit According to Treatment Assignment
timeFrame: End-of-therapy visit. The mean day for this visit was 11.6.
measure: The Mean Score Representing Parental Satisfaction With the Study Medication As Recorded at the Follow-up Visit According to Treatment Assignment
timeFrame: Follow-up visit. The mean day for this visit was 22.8.
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Alejandro Hoberman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hoberman A, Paradise JL, Rockette HE, Shaikh N, Wald ER, Kearney DH, Colborn DK, Kurs-Lasky M, Bhatnagar S, Haralam MA, Zoffel LM, Jenkins C, Pope MA, Balentine TL, Barbadora KA. Treatment of acute otitis media in children under 2 years of age. N Engl J Med. 2011 Jan 13;364(2):105-15. doi: 10.1056/NEJMoa0912254.
citation: Hoberman A, Paradise JL, Shaikh N, Greenberg DP, Kearney DH, Colborn DK, Rockette HE, Kurs-Lasky M, McEllistrem MC, Zoffel LM, Balentine TL, Barbadora KA, Wald ER. Pneumococcal resistance and serotype 19A in Pittsburgh-area children with acute otitis media before and after introduction of 7-valent pneumococcal polysaccharide vaccine. Clin Pediatr (Phila). 2011 Feb;50(2):114-20. doi: 10.1177/0009922810384259. Epub 2010 Nov 22.