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

NCT01511107 | Terminated Phase 2 Results DMC

• 2 other identifiers: 10-0083AI2009058
• Study Type: interventional
• Target: 520
• Locations: 1 country
• Sites: 2

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).

Conditions

Acute Otitis Media

Keywords

acute otitis media; ear infection; antimicrobial therapy; antimicrobial resistance

Outcome Measures

Primary Outcomes (1)

• The Distribution of Children Categorized as Treatment Failure (TF) at or Before the Day 12-14 End-of-Treatment Visit Specific to the Index Episode of AOM

  Proportion of children initially diagnosed with AOM who experience treatment failure at or before the day 12-14 visit. TF is defined as substantial persistence or worsening of symptoms specifically attributable to AOM, or of otoscopic signs of AOM, after 72 hours from the time of randomization, such that additional antimicrobial therapy is deemed advisable. If a parent/legal guardian is unwilling to continue the assigned study product regimen, the participant will be categorized as TF. Should a participant be administered another systemic antibiotic while taking study medication or prior to Day 16, the participant will be considered a TF. Clinical success is defined as complete or substantial resolution of symptoms specifically attributable to AOM for 48 hours and of otoscopic signs of acute inflammation (bulging of the tympanic membrane (TM) or intense erythema), with or without persistence of middle-ear effusion, such that no additional antibiotic therapy is deemed advisable.

  From 72 hours after randomization until day 21 of the index episode. The mean day for this visit was 13.2.

Secondary Outcomes (21)

• The Distribution of AOM Recurrences Categorized as Treatment Failure (TF) at or Before the Day 12-14 End-of-Treatment Visit

  From 72 hours after the AOM recurrence was diagnosed until day 21 of the recurrence. The mean day for this visit was 13.3.

• The Distribution of Children With a Nasopharyngeal (NP) Culture at Enrollment That is Negative for AOM Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen

  The day 12-14 visit. The mean day for this visit was 13.3.

• The Distribution of AOM Recurrences With a Nasopharyngeal (NP) Culture at Onset That is Negative for AOM Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen

  The day 12-14 visit. The mean day for this visit was 13.4.

• The Distribution of Children With a Nasopharyngeal (NP) Culture at Enrollment That is Positive Only for One or More Susceptible Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen

  The day 12-14 visit. The mean day for this visit was 13.2.

• The Distribution of AOM Recurrences With a Nasopharyngeal (NP) Culture at Onset That is Positive Only for One or More Susceptible Pathogens in Which the Follow-up NP Culture at Day 12-14 Yields a Nonsusceptible Pathogen

  The day 12-14 visit. The mean day for this visit was 13.9.

Study Arms (2)

Amoxicillin-Clavulanate, 10 days

ACTIVE COMPARATOR

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

Drug: Amoxicillin-Clavulanate, 10 days

Amoxicillin-Clavulanate, 5 days

OTHER

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

Drug: Amoxicillin-Clavulanate, 5 days

Interventions

Amoxicillin-Clavulanate, 10 days DRUG

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

Also known as: augmentin, amox-clav

Amoxicillin-Clavulanate, 10 days

Amoxicillin-Clavulanate, 5 days DRUG

Amoxicillin-clavulanate (90/6.4mg/kg/day in 2 divided doses) Days 1-5 Plus Placebo Days 6-10

Also known as: augmentin, amox-clav

Amoxicillin-Clavulanate, 5 days

Eligibility Criteria

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

You may qualify if:

• Aged 6 through 23 months
• 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:
• + bulging of the tympanic membrane with either intense erythema or otalgia
• + or 3+ bulging of the tympanic membrane
• Has received at least 2 doses of pneumococcal conjugate vaccine
• Parent has provided informed consent

You may not qualify if:

• Toxic appearance \[capillary refill \>3 seconds, systolic blood pressure \<60 mm Hg\];
• Inpatient hospitalization
• Clinical or anatomical characteristics that might obscure response to treatment (tympanostomy tubes in place, cleft palate, or Down syndrome)
• Sensorineural hearing loss (unilateral or bilateral)
• Serious underlying systemic problems that might obscure response to infection (cystic fibrosis, neoplasm, juvenile diabetes)
• Concomitant infection that would preclude evaluation of the response of the child's AOM to study product (pneumonia, periorbital cellulitis)
• Acute wheezing exacerbation which may require treatment with systemic corticosteroids
• Known renal or hepatic dysfunction or insufficiency
• History of amoxicillin-clavulanate-associated cholestatic jaundice
• Immune dysfunction or receipt of immunosuppressive therapy; chronic gastrointestinal conditions (i.e., malabsorption, inflammatory bowel disease)
• 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)
• Hypersensitivity to penicillin, amoxicillin or amoxicillin-clavulanate, or phenylketonuria or known hypersensitivity to aspartame
• Unable to complete study, or no access to phone
• Previously enrolled in this study or currently enrolled in another study

Sponsors & Collaborators

• Alejandro Hoberman: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (2)

Kentucky Pediatric/Adult Research

Bardstown, Kentucky, 40004, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, 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, 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.

  PMID: 28002709 DERIVED

• 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.

  PMID: 24911895 DERIVED

MeSH Terms

Conditions

Otitis Media; Otitis

Interventions

Amoxicillin-Potassium Clavulanate Combination

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Alejandro Hoberman
• Organization: Children's Hospital of Pittsburgh of UPMC

hobermana@upmc.edu

412-692-5249

Study Officials

• Alejandro Hoberman, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: January 10, 2012
• First Posted: January 18, 2012
• Study Start: January 1, 2012
• Primary Completion: September 1, 2015
• Study Completion: October 1, 2015
• Last Updated: October 6, 2017
• Results First Posted: February 10, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)