Efficacy of Short-Course Antimicrobial Treatment for Children With Acute Otitis Media and Impact on Resistance

NCT ID: NCT01511107

Last Updated: 2017-10-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 520 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2015-10-31

Brief Summary

The investigators will study whether, in young children with acute otitis media (AOM), shortening length of antibiotic treatment as a strategy for reducing antimicrobial resistance provides satisfactory clinical outcome. This is a Phase 2b multicenter, randomized, double-blind, placebo-controlled clinical trial in 600 children aged 6 through 23 months comparing the efficacy of consistent reduced-duration antimicrobial treatment (5 days) with that of consistent standard-duration treatment (10 days) for each episode of AOM developing during a single respiratory season (October 1 through May 31).

Detailed Description

Eligible subjects will be randomized at the enrollment visit and will have a telephone call in the course of therapy, and a subsequent visit at the end of therapy. Thereafter, they will be followed through the end of the respiratory season, and their parents will be encouraged to bring their child when concerned about a potential recurrence of AOM. At each recurrence subjects will receive the treatment regimen (either standard- or reduced-duration) to which they were randomized at study entry (consistent treatment strategy).

The recruitment of eligible children with AOM of varying degrees of severity from various primary care practices in 2 separate geographic regions, i.e. Western Pennsylvania and Kentucky, representing urban, suburban and rural demographics will enhance generalizability of study findings and encourage translation to clinical practice.

Conditions

Acute Otitis Media

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Amoxicillin-Clavulanate, 10 days

amoxicillin-clavulanate, 90/6.4 mg/kg/day, 2 divided doses, 10 days

Group Type: ACTIVE_COMPARATOR

Amoxicillin-Clavulanate, 10 days

Intervention Type: DRUG

Amoxicillin-clavulanate (90/6.4mg/kg/day in 2 divided doses) Days 1-10

Amoxicillin-Clavulanate, 5 days

amoxicillin-clavulanate, 90/6.4 mg/kg/day, 2 divided doses, 5 days plus placebo, 2 divided doses, 5 days

Group Type: OTHER

Amoxicillin-Clavulanate, 5 days

Intervention Type: DRUG

Amoxicillin-clavulanate (90/6.4mg/kg/day in 2 divided doses) Days 1-5

Plus

Placebo Days 6-10

Interventions

Amoxicillin-Clavulanate, 10 days

Amoxicillin-clavulanate (90/6.4mg/kg/day in 2 divided doses) Days 1-10

Intervention Type: DRUG

Amoxicillin-Clavulanate, 5 days

Amoxicillin-clavulanate (90/6.4mg/kg/day in 2 divided doses) Days 1-5

Plus

Placebo Days 6-10

Intervention Type: DRUG

Other Intervention Names

augmentin; amox-clav; augmentin; amox-clav

Eligibility Criteria

Inclusion Criteria

1. Aged 6 through 23 months

2. Have evidence of AOM defined as:

• recent (within 48 hours) onset of signs and symptoms as described in the Acute Otitis Media - Severity of Symptoms (AOM-SOS) Scale AND a score of ≥3 at the time of enrollment on the AOM-SOS scale
• middle ear effusion evidenced by the presence of at least 2 of the following:
• decreased or absent mobility of the tympanic membrane
• yellow or white discoloration of the tympanic membrane
• opacification of the tympanic membrane

AND

• acute inflammation evidenced by one of the following:
• 1+ bulging of the tympanic membrane with either intense erythema or otalgia
• 2+ or 3+ bulging of the tympanic membrane

3. Has received at least 2 doses of pneumococcal conjugate vaccine

4. Parent has provided informed consent

Exclusion Criteria

1. Toxic appearance [capillary refill >3 seconds, systolic blood pressure <60 mm Hg];

2. Inpatient hospitalization

3. Clinical or anatomical characteristics that might obscure response to treatment (tympanostomy tubes in place, cleft palate, or Down syndrome)

4. Sensorineural hearing loss (unilateral or bilateral)

5. Serious underlying systemic problems that might obscure response to infection (cystic fibrosis, neoplasm, juvenile diabetes)

6. Concomitant infection that would preclude evaluation of the response of the child's AOM to study product (pneumonia, periorbital cellulitis)

7. Acute wheezing exacerbation which may require treatment with systemic corticosteroids

8. Known renal or hepatic dysfunction or insufficiency

9. History of amoxicillin-clavulanate-associated cholestatic jaundice

10. Immune dysfunction or receipt of immunosuppressive therapy; chronic gastrointestinal conditions (i.e., malabsorption, inflammatory bowel disease)

11. Co-medications (systemic corticosteroids, more than one dose of systemic antimicrobial therapy within 96 hours, receipt of any investigational drug or vaccine within 30 days)

12. Hypersensitivity to penicillin, amoxicillin or amoxicillin-clavulanate, or phenylketonuria or known hypersensitivity to aspartame

13. Unable to complete study, or no access to phone

14. Previously enrolled in this study or currently enrolled in another study

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 23 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

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

Locations

Kentucky Pediatric/Adult Research

Bardstown, Kentucky, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 37171965 (View on PubMed)

Hoberman A, Paradise JL, Rockette HE, Kearney DH, Bhatnagar S, Shope TR, Martin JM, Kurs-Lasky M, Copelli SJ, Colborn DK, Block SL, Labella JJ, Lynch TG, Cohen NL, Haralam M, Pope MA, Nagg JP, Green MD, Shaikh N. Shortened Antimicrobial Treatment for Acute Otitis Media in Young Children. N Engl J Med. 2016 Dec 22;375(25):2446-2456. doi: 10.1056/NEJMoa1606043.

Reference Type: DERIVED

PMID: 28002709 (View on PubMed)

Martin JM, Hoberman A, Paradise JL, Barbadora KA, Shaikh N, Bhatnagar S, Shope T, Block SL, Haralam MA, Kurs-Lasky M, Colborn DK, Green M. Emergence of Streptococcus pneumoniae serogroups 15 and 35 in nasopharyngeal cultures from young children with acute otitis media. Pediatr Infect Dis J. 2014 Nov;33(11):e286-90. doi: 10.1097/INF.0000000000000445.

Reference Type: DERIVED

PMID: 24911895 (View on PubMed)

Other Identifiers

AI2009058

Identifier Type: OTHER

Identifier Source: secondary_id

10-0083

Identifier Type: -

Identifier Source: org_study_id