Efficacy of Tympanostomy Tubes for Children With Recurrent Acute Otitis Media

NCT ID: NCT02567825

Last Updated: 2022-07-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2021-02-28

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.

Conditions

Acute Otitis Media

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Surgical Management

Tympanostomy Tube Placement Topical antimicrobial treatment of acute otitis media episodes with ofloxacin drops

Group Type: ACTIVE_COMPARATOR

Tympanostomy tube placement

Intervention Type: DEVICE

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.

Ofloxacin Otic

Intervention Type: DRUG

Participants randomized to receive tympanostomy 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

Group Type: OTHER

Amoxicillin-Clavulanate and/or Ceftriaxone

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DEVICE

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.

Intervention Type: DRUG

Ofloxacin Otic

Participants randomized to receive tympanostomy 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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 35 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

George Washington University

OTHER

Sponsor Role: collaborator

National Institute on Deafness and Other Communication Disorders (NIDCD)

NIH

Sponsor Role: collaborator

Alejandro Hoberman

OTHER

Sponsor Role: lead

Responsible Party

Alejandro Hoberman

Professor of Pediatrics

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Alejandro Hoberman, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh School of Medicine; Children's Hospital of Pittsburgh of UPMC

Diego Preciado, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

George Washington University; Childrens National Medical Center

Locations

Children's National Medical Center

Washington D.C., District of Columbia, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Countries

United States

References

Noorbakhsh KA, Liu H, Kurs-Lasky M, Smith KJ, Hoberman A, Shaikh N. Cost-Effectiveness of Management Strategies in Recurrent Acute Otitis Media. J Pediatr. 2023 May;256:11-17.e2. doi: 10.1016/j.jpeds.2022.11.032. Epub 2022 Dec 5.

Reference Type: DERIVED

PMID: 36470464 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33979487 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1U01DC013995-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PRO15060148

Identifier Type: -

Identifier Source: org_study_id