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Efficacy of Tympanostomy Tubes for Children With Recurrent Acute Otitis Media

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02567825
Recruitment Status : Completed
First Posted : October 5, 2015
Last Update Posted : March 22, 2021
George Washington University
National Institute on Deafness and Other Communication Disorders (NIDCD)
Information provided by (Responsible Party):
Alejandro Hoberman, University of Pittsburgh

Brief Summary:
To determine whether tympanostomy tube placement (TTP) compared with nonsurgical management will meaningfully improve children's acute otitis media (AOM) experience over the succeeding 2 years.

Condition or disease Intervention/treatment Phase
Acute Otitis Media Device: Tympanostomy tube placement Drug: Amoxicillin-Clavulanate and/or Ceftriaxone Drug: Ofloxacin Otic Not Applicable

Detailed Description:
Tympanostomy tube placement (TTP) for recurrent acute otitis media (rAOM) is frequently performed in children under 3 years of age; however, a critical need exists to establish its risk/benefit ratio. Seventy percent of children experience at least one episode of AOM during the first year of life; 20% of children have rAOM. The efficacy of TTP for preventing rAOM, assumedly by maintaining middle-ear ventilation, remains unclear. Benefits of TTP must be balanced against risks of anesthesia, complications and sequelae of surgery, and cost. Accordingly, the objective of this proposal is to determine the efficacy of TTP in children aged 6-35 months, the group in which rAOM is most troublesome. The central hypothesis is that in children with rAOM, the operation will prove effective over the ensuing 2 years overall, but the benefit in a more severely affected, and therefore higher-risk subgroup may be substantially greater than in a less severely affected subgroup, in whom benefits may not outweigh risks. The rationale for this research is based on a belief that the limited nature of the benefit of TTP found in earlier clinical trials may have been the result of enrolling children whose illnesses had not been diagnosed using stringent criteria and/or whose ascertainment of episodes had relied on undocumented histories. The primary objective is to determine the extent to which TTP reduces the overall rate of recurrences in children with rAOM over a 2-year period. In a randomized, clinical trial, children aged 6-35 months who are at risk for rAOM will be followed prospectively and examined promptly with new respiratory illnesses to accurately document episodes of AOM. A total of 240 children who meet stringent inclusion criteria for rAOM will be eligible to undergo randomization within strata (age and exposure to other children) to receive TTP or nonsurgical management. Children will be followed for 2 years; the average number of episodes of AOM will be documented and compared between groups. The secondary objective is to determine changes following TTP in nasopharyngeal (NP) colonization with resistant bacteria. At the time of randomization and 3 times a year for 2 years, NP specimens will be obtained and cultured. Susceptibility testing and serotyping will be performed, and the proportions of children colonized with resistant bacteria compared between treatment groups. The tertiary objective is to determine cost-effectiveness of TTP. The investigators will calculate both direct medical and nonmedical costs and correlate this with the number of days that each child has AOM symptoms, otorrhea, and any adverse events or complications. The proposed research is innovative, as the investigators will document AOM episodes prospectively using stringent diagnostic criteria and obtain digital tympanic membrane images otoendoscopically to enhance accuracy of observations. Findings of the proposed study will provide clinicians and parents with dependable evidence concerning the overall effects of TTP compared with nonsurgical management in children with rAOM of varying degrees of severity, enabling evidence-based decisions regarding an important component of the children's healthcare.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description: Subjects in the randomization phase of the study will be randomized to either medical management or tube surgery. No masking will occur.
Primary Purpose: Treatment
Official Title: Efficacy of Tympanostomy Tubes for Children With Recurrent Acute Otitis Media
Study Start Date : November 2015
Actual Primary Completion Date : March 2020
Actual Study Completion Date : February 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ear Infections

Arm Intervention/treatment
Active Comparator: Surgical Management
Tympanostomy Tube Placement Topical antimicrobial treatment of acute otitis media episodes with ofloxacin drops
Device: Tympanostomy tube placement
As per routine care, tympanostomy tubes will be inserted under general anesthesia, using a small radial incision in the anteroinferior portion of the tympanic membrane; a Teflon® Armstrong-type tympanostomy tube will be used.

Drug: Ofloxacin Otic
Participants randomized to receive tympanovstomy tubes will also be followed overtime for recurrences of AOM and treated with topical ofloxacin (Floxin® 0.3%, 5 mL) 5 drops into the affected ear twice daily for 10 days. Persistence of otorrhea after 7 days of treatment will be considered inadequate response, and children so affected will be prescribed empiric amoxicillin-clavulanate (90/6.4 mg/kg/day in two divided doses) followed by culture-directed therapy 48 hours later.

Non-Surgical Management
Antimicrobial treatment of acute otitis media episodes with amoxicillin-clavulanate and/or ceftriaxone
Drug: Amoxicillin-Clavulanate and/or Ceftriaxone
Children randomized to nonsurgical management will receive stepwise therapy with amoxicillin-clavulanate (90/6.4 mg/kg in two divided doses for 10 days), and in the event of inadequate response, ceftriaxone (75 mg/kg intramuscularly, repeated in 48 hours), as recommended in the American Academy of Pediatrics guidelines.

Primary Outcome Measures :
  1. Acute Otitis Media rate [ Time Frame: 2 years ]
    Average number of AOM episodes during the 2-year follow-up period.

Secondary Outcome Measures :
  1. Severity of AOM episodes per American Academy of Pediatrics definitions [ Time Frame: 2 years ]
    Comparison of the proportion of AOM recurrences categorized as severe vs. non-severe using the American Academy of Pediatrics definition (severe, indicated by moderate or severe otalgia or temperature ≥39°C vs. non-severe, indicated by mild otalgia or temperature <39°C).

  2. Severity of AOM episodes per AOM-Severity of Symptoms Score [ Time Frame: 2 years ]
    Comparison of AOM-Severity of Symptoms scores at Days 1 and Day 5 of AOM recurrences

  3. Frequency distribution of AOM recurrences [ Time Frame: 2 years ]
  4. Time to first AOM recurrence [ Time Frame: 2 years ]
  5. Type of recurrences [ Time Frame: 2 years ]
    Proportion of AOM recurrences presenting with intact bulging tympanic membrane or tube otorrhea

  6. Antibiotic utilization [ Time Frame: 2 years ]
    Total days per year subjects receive systemic antimicrobials for AOM

  7. Selected adverse events [ Time Frame: 2 years ]
    Proportion of children with selected adverse events (protocol defined diarrhea, diaper dermatitis, chronic otorrhea)

  8. Antibiotic resistance of nasopharyngeal pathogens [ Time Frame: 2 years ]
    Secondary endpoints concerning resistance include (1) proportion of children whose nasopharyngeal cultures at randomization are, respectively, either negative for S. pneumoniae and H. influenzae, or positive for penicillin-susceptible pathogens, or positive for one or more penicillin-nonsusceptible pathogens, who subsequently are found on a follow-up nasopharyngeal culture to harbor one or more penicillin-nonsusceptible pathogens; (2) proportion of interim, non-illness visits at which a penicillin-nonsusceptible pathogen is recovered; and (3) for all AOM episodes, the proportions of S. pneumoniae and H. influenzae isolates recovered at a visit during April or May (end of the respiratory season) that are penicillin nonsusceptible.

  9. Cost-effectiveness [ Time Frame: 2 years ]
    Greater cost-effectiveness in children at higher-risk for rAOM than in children at lower-risk. Cost effectiveness of each treatment strategy will be calculated by dividing the costs of each strategy by its effectiveness.

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Ages Eligible for Study:   6 Months to 35 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria

  1. are aged 6-35 months,
  2. have rAOM, defined as the occurrence of 3 AOM episodes in 6 months or 4 episodes in 12 months with ≥1 episode in the preceding 6 months, and
  3. 2 of these AOM episodes have been documented by trained study personnel.

Exclusion Criteria

  1. have a history of TTP,
  2. have a chronic illness (cystic fibrosis, neoplasm, juvenile diabetes, renal or hepatic insufficiency, immune dysfunction, malabsorption, inflammatory bowel disease, severe asthma requiring at least 4 courses of oral corticosteroids during the last 12 months),
  3. are allergic to amoxicillin,
  4. have a congenital anomaly that might increase the risk of recurrences (e.g., cleft palate, Down's syndrome),
  5. have had otitis media effusion for at least 3 months in addition to rAOM, or
  6. have sensorineural hearing loss.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02567825

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United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
Sponsors and Collaborators
Alejandro Hoberman
George Washington University
National Institute on Deafness and Other Communication Disorders (NIDCD)
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Principal Investigator: Alejandro Hoberman, MD University of Pittsburgh School of Medicine; Children's Hospital of Pittsburgh of UPMC
Principal Investigator: Diego Preciado, MD, PhD George Washington University; Childrens National Medical Center
  Study Documents (Full-Text)

Documents provided by Alejandro Hoberman, University of Pittsburgh:
Informed Consent Form: Randomization  [PDF] April 5, 2018
Informed Consent Form: Screening  [PDF] April 5, 2018

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Responsible Party: Alejandro Hoberman, Professor of Pediatrics, University of Pittsburgh Identifier: NCT02567825    
Other Study ID Numbers: PRO15060148
1U01DC013995-01A1 ( U.S. NIH Grant/Contract )
First Posted: October 5, 2015    Key Record Dates
Last Update Posted: March 22, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Keywords provided by Alejandro Hoberman, University of Pittsburgh:
ear infection
tympanostomy tubes
Additional relevant MeSH terms:
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Otitis Media
Ear Diseases
Otorhinolaryngologic Diseases
Clavulanic Acid
Clavulanic Acids
Amoxicillin-Potassium Clavulanate Combination
Anti-Bacterial Agents
Anti-Infective Agents
beta-Lactamase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Renal Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors