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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2012 by University of Pittsburgh
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alejandro Hoberman, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01511107
First received: January 10, 2012
Last updated: January 13, 2012
Last verified: January 2012
  Purpose

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).


Condition Intervention Phase
Acute Otitis Media
Drug: Amoxicillin-Potassium Clavulanate Combination
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2b, Multicenter, Randomized, Double Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy of Short-Course Antimicrobial Therapy for Young Children With Acute Otitis Media (AOM) and Impact on Antimicrobial Resistance

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Treatment Failure (Index Episode of AOM) [ Time Frame: From 72 hours after randomization until Day 16 of the index episode ] [ Designated as safety issue: No ]

    Proportion of subjects initially diagnosed with AOM who receive, respectively, reduced-duration treatment (5 days of amoxicillin-clavulanate potassium followed by 5 days of placebo), and standard-duration treatment (10 days of amoxicillin-clavulanate potassium) who experience treatment failure at or before the visit on Day 12-14.

    Treatment failure will be 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.



Secondary Outcome Measures:
  • Nasopharyngeal Colonization with Resistant Pathogens [ Time Frame: a. From Day 1 of administration of study product until Day 16 (all episodes); b. From Day 1 of study entry until Day 365; c. From Day 45 after randomization until Day 365; d. From Day 10 of administration of study product until Day 16 (all episodes) ] [ Designated as safety issue: No ]

    Proportion of:

    1. AOM episodes with nasopharyngeal (NP) culture at onset that is 1) negative; or 2) positive for penicillin (PCN) -susceptible pathogens; or 3) positive for PCN-nonsusceptible pathogens, in which the NP culture at day 12-14 yields a PCN-nonsusceptible pathogen.
    2. Subjects whose entry NP isolates are negative or PCN-susceptible, who become colonized with PCN-nonsusceptible pathogens.
    3. Cultures at non-illness visits with a PCN-nonsusceptible pathogen.
    4. S. pneumoniae and H. influenzae isolates at Day 12-14 that are, respectively, nonsusceptible and B-lactamase positive.

  • AOM Recurrence [ Time Frame: From Day 17 after randomization up to Day 228 ] [ Designated as safety issue: No ]

    Proportion of subjects with AOM recurrences within 60 days of enrollment and within a single respiratory season (October 1 through May 31).

    Mean number of AOM recurrences within 60 days of enrollment and within a single respiratory season (October 1 through May 31).


  • Antibiotic Use [ Time Frame: From randomization up to Day 244 ] [ Designated as safety issue: No ]
    Mean number of days receiving antibiotics during a single respiratory season (October 1 through May 31)

  • Symptom Burden [ Time Frame: From Day 6 of administration of study product until Day 14 (all episodes) ] [ Designated as safety issue: No ]
    Daily mean AOM-Severity of Symptom scale [AOM-SOS] scores between Day 6 and Day 14.

  • Treatment Failure (AOM Recurrences) [ Time Frame: From 72 hours of first dose of study product until Day 16 ] [ Designated as safety issue: No ]
    Proportion of AOM recurrences in which treatment failure occurs at or before the visit on Day 12-14.

  • Protocol-Defined Diarrhea and Diaper Dermatitis [ Time Frame: Day 1 of administration of study product until Day 16 (all episodes) ] [ Designated as safety issue: Yes ]
    Proportion of subjects with protocol-defined diarrhea (the occurrence of three or more watery stools in 1 day or two watery stools daily for at least 2 days) and diaper dermatitis resulting in the prescription of a topical anti-fungal medication.


Estimated Enrollment: 600
Study Start Date: January 2012
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard-Duration Therapy (10 days) Drug: Amoxicillin-Potassium Clavulanate Combination
Amoxicillin-clavulanate potassium (600/42.9 mg per 5 mL), administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for 10 days.
Experimental: Reduced-Duration Therapy (5 days) Drug: Amoxicillin-Potassium Clavulanate Combination
Amoxicillin-clavulanate potassium (600/42.9 mg per 5 mL), administered at a dosage of 90/6.4mg/kg/day in 2 divided doses for Days 1-5 followed by placebo in 2 divided doses for Days 6-10.

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 PA and Kentucky, representing urban, suburban and rural demographics will enhance generalizability of study findings and encourage translation to clinical practice.

  Eligibility

Ages Eligible for Study:   6 Months to 23 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01511107

Contacts
Contact: Alejandro Hoberman, MD hoberman@chp.edu

Locations
United States, Kentucky
Kentucky Pediatric/Adult Research Recruiting
Bardstown, Kentucky, United States, 40004
Contact: Stanley Block, MD       slblock@pol.net   
Contact: Marty Patterson, RN, CCRC    502-349-1569 ext 1218    mpatterson.kpar@bardstowncable.net   
Principal Investigator: Stanley Block, MD         
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Alejandro Hoberman, MD    412-999-3277    hoberman@chp.edu   
Contact: Diana Kearney, CCRC    412-692-6717    Diana.Kearney@chp.edu   
Principal Investigator: Alejandro Hoberman, MD         
Sponsors and Collaborators
Alejandro Hoberman
Investigators
Principal Investigator: Alejandro Hoberman, MD University of Pittsburgh
  More Information

No publications provided

Responsible Party: Alejandro Hoberman, Professor of Pediatrics, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01511107     History of Changes
Other Study ID Numbers: 10-0083
Study First Received: January 10, 2012
Last Updated: January 13, 2012
Health Authority: United States: Food and Drug Administration
United States: Federal Government
United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
acute otitis media
ear infection
antimicrobial therapy
antimicrobial resistance

Additional relevant MeSH terms:
Anti-Infective Agents
Anti-Bacterial Agents
Otitis
Otitis Media
Ear Diseases
Otorhinolaryngologic Diseases
Clavulanic Acids
Clavulanic Acid
Amoxicillin
Amoxicillin-Potassium Clavulanate Combination
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014