Clinical trial NCT02567825: Efficacy of Tympanostomy Tubes for Children With Recurrent Acute Otitis Media
Official title: Efficacy of Tympanostomy Tubes for Children With Recurrent Acute Otitis Media
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Otitis Media
Keywords: ear infection
antibiotics
infants
children
pediatrics
tympanostomy tubes
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: George Washington University
name: National Institute on Deafness and Other Communication Disorders (NIDCD)
First posted: 2015-10-05
Enrollment: 250
Sex: ALL
Minimum age (years): 6
Maximum age (years): 35
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The Rate of Occurrence of Acute Otitis Media (AOM) Episodes Per Child-Year
timeFrame: Day 1 until Day 786. The mean length of actual follow-up was 662 days / 1.8 years. For each child with incomplete 2-year follow-up, multiple imputation was used and values for the remaining days/years were imputed.
Secondary outcomes:
measure: The Rate of Occurrence of Acute Otitis Media (AOM) Episodes Per Child-Year According to the Estimated Risk of Acute Otitis Media (AOM) Recurrences at Enrollment
timeFrame: Day 1 until Day 786. The mean length of actual follow-up was 662 days / 1.8 years. For each child with incomplete 2-year follow-up, multiple imputation was used and values for the remaining days/years were imputed.
measure: The Frequency Distribution of AOM Episodes Among Children Completing the Study
timeFrame: Day 1 until Day 786. For children completing the study, the mean length of follow-up was 726 days.
measure: The Distribution of Children Experiencing Treatment Failure (TF)
timeFrame: Day 1 until Day 786.
measure: The Time to the First Episode of AOM
timeFrame: Day 1 until Day 786. The mean length of follow-up was 662 days / 21.8 months.
measure: The Distribution of AOM Episodes Categorized as Probably Severe or Probably Nonsevere
timeFrame: Day 1 until Day 786.
measure: The Distribution of AOM Episodes Presenting With Tympanic Membrane Bulging or Otorrhea
timeFrame: Day 1 until Day 786.
measure: The Mean Days Per Year Children Experience Tube Otorrhea
timeFrame: Day 1 until Day 786. The mean length of follow-up was 662 days / 1.8 years.
measure: The Mean Days Per Year Children Experience AOM Symptoms With an Intact Tympanic Membrane (TM)
timeFrame: Day 1 until Day 786. The mean length of follow-up was 662 days / 1.8 years.
measure: The Mean Days Per Year Children Receive Systemic Antimicrobials for AOM
timeFrame: Day 1 until Day 786. The mean length of follow-up was 662 days / 1.8 years.
measure: The Distribution of Children for Whom Protocol-Defined Diarrhea (PDD) Was Reported
timeFrame: Day 1 until Day 786.
measure: The Distribution of Children for Whom Diaper Dermatitis Was Reported
timeFrame: Day 1 until Day 786.
measure: The Distribution of Children for Whom Tube Otorrhea Was Reported
timeFrame: Day 1 until Day 786.
measure: The Distribution of Children With a Penicillin-Nonsusceptible Nasopharyngeal or Throat Isolate At Any Follow-up Visit According to the Colonization Status at Enrollment
timeFrame: Day 1 until Day 786.
measure: The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at Episodes of AOM
timeFrame: Day 1 until Day 786.
measure: The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at Routine Non-Illness Visits
timeFrame: Day 1 until Day 786.
measure: The Distribution of Nonsusceptible Nasopharyngeal or Throat Pathogens Recovered at AOM Episodes Late During the Respiratory Season (April-May)
timeFrame: April 1 to May 31, each of the 2 years of follow-up. The mean length of follow-up was 111 days / 3.7 months.
measure: The Mean Score Representing Parental Satisfaction With Clinical Management
timeFrame: The end-of-study visit. The mean day for this visit was 726.
measure: The Distribution of Parent Reports Indicating At Least One Health Care Encounter Since the Previous Study Visit as an Indicator of Medical Resource Use
timeFrame: Day 1 until Day 786.
measure: The Distribution of Reported Occurrences of a Parent Missing Work Due to Child's Illness, as an Indicator of Non-Medical Resource Use
timeFrame: Day 1 until Day 786.
measure: The Distribution of Reported Occurrences of the Need for Special Childcare Arrangements Due to Child's Illness, as an Indicator of Non-Medical Resource Use
timeFrame: Day 1 until Day 786.
measure: The Mean Scores on the 6 Item Quality of Life Survey Questionnaire (OM-6)
timeFrame: Day 1 until Day 786.
measure: The Mean Scores on the 6 Item Caregiver Impact Questionnaire (CIQ)
timeFrame: Day 1 until Day 786.
measure: The Total Cost of Management of Recurrent Acute Otitis Media Per Quality Adjusted Life Days (QALDs) as a Measure of Cost-Effectiveness
timeFrame: Day 1 until Day 786. The mean length of actual follow-up was 662 days / 1.8 years.
measure: The Total Cost of Management of Recurrent Acute Otitis Media Per Quality Adjusted Life Days (QALDs) as a Measure of Cost-Effectiveness According to the Estimated Risk of Acute Otitis Media Recurrences at Enrollment
timeFrame: Day 1 until Day 786. The mean length of actual follow-up was 662 days / 1.8 years.
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh School of Medicine; Children's Hospital of Pittsburgh of UPMC
name: Alejandro Hoberman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: George Washington University; Childrens National Medical Center
name: Diego Preciado, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hoberman A, Preciado D, Paradise JL, Chi DH, Haralam M, Block SL, Kearney DH, Bhatnagar S, Muniz Pujalt GB, Shope TR, Martin JM, Felten DE, Kurs-Lasky M, Liu H, Yahner K, Jeong JH, Cohen NL, Czervionke B, Nagg JP, Dohar JE, Shaikh N. Tympanostomy Tubes or Medical Management for Recurrent Acute Otitis Media. N Engl J Med. 2021 May 13;384(19):1789-1799. doi: 10.1056/NEJMoa2027278.