Acute Otitis Media (AOM) Therapy Trial in Young Children

NCT00377260 | Completed Phase 4 Results DMC

• 2 other identifiers: 05-0142U01AI066007
• Study Type: interventional
• Target: 291
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Otitis Media

Keywords

acute otitis media, infants, children

Outcome Measures

Primary Outcomes (3)

• 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

  Time to resolution of symptoms is defined as the time from randomization until a child's AOM-SOS score reaches 0 or 1. The parent rated each of 7 symptoms (ear tugging, crying, irritability, difficulty sleeping, diminished activity, diminished appetite \& fever) as 0, 1 or 2 (none, a little, a lot) and recorded the ratings in a diary following enrollment on Day 1, twice daily Days 2 and 3, then once daily Days 4-7. Each set of ratings was summed to obtain an AOM-SOS score. The maximum possible score was 14 and the minimum was 0. A score \>=3 was required to be enrolled in the study.

  The first 7 days on therapy

• 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

  Time to resolution of symptoms is defined as the time from randomization until a child's AOM-SOS score reaches \<= 1 on two consecutive occasions. The parent rated each of 7 symptoms (ear tugging, crying, irritability, difficulty sleeping, diminished activity, diminished appetite \& fever) as 0, 1 or 2 (none, a little, a lot) \& recorded the ratings in a diary following enrollment on Day 1, twice daily Days 2 \& 3, \& once daily Days 4-7. Each set of ratings was summed to obtain an AOM-SOS score. The maximum possible was 14 and the minimum 0. A score \>=3 was required to be enrolled in the study.

  The first 7 days on therapy

• The Weighted Average Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, According to Treatment Assignment

  The AOM-SOS score is derived from parent scoring each of 7 symptoms (ear tugging, crying, irritability, difficulty sleeping, diminished activity, diminished appetite \& fever) associated with AOM as 0, 1 or 2 (none, a little, a lot). The AOM-SOS was administered twice daily the first 3 days of follow-up, then daily for 4 additional days. Symptom burden for each child is determined by calculating the weighted average of symptom scores post-enrollment over the first 7 days of therapy. Scores are weighted by 1/k, where k is the number of post-enrollment assessments taken on that day.

  During the first 7 days of therapy

Secondary Outcomes (21)

• The Distribution of Clinical Failures by the On-therapy Visit According to Treatment Assignment

  On-therapy visit. The mean day for this visit was 5.0.

• The Distribution of Clinical Failures by the End-of-therapy Visit According to Treatment Assignment

  End-of-therapy visit. The mean day for this visit was 11.6.

• The Mean Acute Otitis Media - Severity of Symptom (AOM-SOS) Score, Post-enrollment, Over the First 7 Days of Therapy According to Treatment Assignment

  During the first 7 days of therapy

• The Distribution of Children Developing Worsening Symptoms Prior to Receiving 72 Hours of Study Medication According to Treatment Assignment

  Before receiving 72 hours of study medication

• The Mean Number of Times Analgesic Medication Was Administered to the Child According to Treatment Assignment

  The first 10 days of follow-up

Study Arms (2)

Amoxicillin-clavulanate

EXPERIMENTAL

Reconstituted amoxicillin-clavulanate at 90/6.4 mg/kg/day in 2 divided doses for 10 days.

Drug: amoxicillin-clavulanate

Placebo

PLACEBO COMPARATOR

Reconstituted placebo in 2 divided doses for 10 days.

Drug: Placebo

Interventions

amoxicillin-clavulanate DRUG

Augmentin ES-600™: Amoxicillin-clavulanate potassium (600/42.9 mg per 5 mL), administered at a dose of 90/6.4 mg/kg/day in 2 divided doses for 10 days with strawberry cream flavor.

Also known as: Augmentin, amox-clav

Amoxicillin-clavulanate

Placebo DRUG

Same base formulation of the licensed product Augmentin ES-600™, with the same strawberry cream flavor.

Placebo

Eligibility Criteria

• Age: 6 Months - 23 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• + bulging of the tympanic membrane with either marked erythema or otalgia, or
• + or 3+ bulging of the tympanic membrane

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (3)

• Shaikh N, Hoberman A, Paradise JL, Rockette HE, Kurs-Lasky M, Martin JM. Association Between Nasopharyngeal Colonization and Clinical Outcome in Children With Acute Otitis Media. Pediatr Infect Dis J. 2023 Aug 1;42(8):e274-e277. doi: 10.1097/INF.0000000000003956. Epub 2023 Apr 26.

  PMID: 37171965 DERIVED

• 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.

  PMID: 21226576 DERIVED

• 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.

  PMID: 21098526 DERIVED

MeSH Terms

Conditions

Otitis Media

Interventions

Amoxicillin-Potassium Clavulanate Combination

Condition Hierarchy (Ancestors)

Otitis; Ear Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Clavulanic Acid; Clavulanic Acids; beta-Lactams; Lactams; Amides; Organic Chemicals; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Limitations and Caveats

Long-term implications of abnormal otoscopic findings (bulging) without symptoms, and persistent middle-ear effusion without findings of acute inflammation as forerunners of subsequent acute otitis media episodes remains uncertain.

Results Point of Contact

• Title: Efficacy of Antimicrobials in Young children with Acute Otitis Media
• Organization: Children's Hospital of Pittsburgh of UPMC

Hoberman@chp.edu

412-692-5249

Study Officials

• Alejandro Hoberman, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Division of General Academic Pediatrics

Study Record Dates

• First Submitted: September 14, 2006
• First Posted: September 18, 2006
• Study Start: November 1, 2006
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: December 5, 2016
• Results First Posted: August 11, 2010

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)