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Effect of Antimicrobial Treatment of Acute Otitis Media on the Intestinal Microbiome in Children (AOMMi)

Primary Purpose

Acute Otitis Media

Status
Completed
Phase
Phase 4
Locations
Finland
Study Type
Interventional
Intervention
Amoxicillin
Amoxicillin-Potassium Clavulanate
Macrolide
Sponsored by
University of Oulu
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Acute Otitis Media focused on measuring children, intestinal microbiome, microbiota, antimicrobial course, amoxicillin, amoxicillin-clavulanate, macrolide

Eligibility Criteria

6 Months - 7 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • acute symptoms of respiratory infection AND
  • signs of inflammation on the tympanic membrane in otoscopy AND
  • middle ear effusion found in pneumatic otoscopy

Exclusion Criteria:

  • Suspected or proven complication of acute otitis media (for example acute mastoiditis or perforated tympanic membrane)
  • Severe acute otitis media: severe pain and fever > 39 degrees C
  • Bilateral acute otitis media in a child younger than 2 years
  • Primary or secondary immunodeficiency or Downs syndrome
  • Impaired general condition or suspected severe bacterial infection
  • Allergy to both amoxicillin and macrolide
  • Acute otorrhea through tympanostomy tube
  • Antimicrobial treatment ongoing or during previous 7 days

Sites / Locations

  • Mehiläinen, private practice

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

No Intervention

Other

Arm Label

Amoxicillin

Amoxicillin-Potassium Clavulanate

Wait and see

Macrolide

Arm Description

The children with acute otitis media will be treated with amoxicillin mixture, 100mg/ml, 40mg/kg/d, divided to two daily doses for 7 days.

The children with acute otitis media will be treated with amoxicillin-clavulanate mixture, 80mg/ml, 45mg/kg/d, divided to two daily doses for 7 days.

The children with acute otitis media will be monitored without antimicrobial treatment.

The children with acute otitis media with known allergy to amoxicillin or amoxicillin-clavulanate will be treated with macrolide and monitored as a separate group, outside randomization.

Outcomes

Primary Outcome Measures

Change in the relative abundance of Firmicutes in stool samples
Change in the relative abundance of Firmicutes in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.

Secondary Outcome Measures

Principal coordinate analysis (PCA) of fecal samples
Principal coordinate analysis (PCA) of the microbiota of fecal samples 10 days after starting treatment to acute otitis media
Change in the relative abundance of Actinobacteria in stool samples
Change in the relative abundance of Actinobacteria in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
Change in the relative abundance of Bacteroidetes in stool samples
Change in the relative abundance of Bacteroidetes in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
Change in the relative abundance of Proteobacteria in stool samples
Change in the relative abundance of Proteobacteria in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
Change in the relative abundance of Verrucomicrobia in stool samples
Change in the relative abundance of Verrucomicrobia in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
Change in the relative abundance of Lactobacilli in stool samples
Change in the relative abundance of Lactobacilli in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
Change in the relative abundance of Bifidobacteria in stool samples
Change in the relative abundance of Bifidobacteria in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
Change in the relative abundance of Faecalibacterium prausnitzii in stool samples
Change in the relative abundance of Faecalibacterium prausnitzii in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
Change in the diversity of fecal microbiota measured with the number of operational taxonomic units (OTUs)
Change in the diversity of fecal microbiota measured with the number of operational taxonomic units (OTUs) from baseline to 10 days after the diagnosis of acute otitis media
Change in the diversity of fecal microbiota measured with Shannon index
Change in the diversity of fecal microbiota measured with Shannon index from baseline to 10 days after the diagnosis of acute otitis media
Change in the diversity of fecal microbiota measured with Chao index
Change in the diversity of fecal microbiota measured with Chao index from baseline to 10 days after the diagnosis of acute otitis media
Presence of antimicrobial genes measured with the means of metagenomics
Presence of antimicrobial genes measured with the means of metagenomics at 10 days after the diagnosis of acute otitis media
Proportion of Clostridium difficile -positive fecal samples
Occurrence of Clostridium difficile in fecal samples 10 days after the diagnosis of acute otitis media
Proportion of fecal samples with Extended Spectrum Beta-Lactamase -positive strains
Proportion of fecal samples with Extended Spectrum Beta-Lactamase -positive strains 10 days after the diagnosis of acute otitis media

Full Information

First Posted
September 28, 2016
Last Updated
August 8, 2022
Sponsor
University of Oulu
Collaborators
Oulu University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02935374
Brief Title
Effect of Antimicrobial Treatment of Acute Otitis Media on the Intestinal Microbiome in Children
Acronym
AOMMi
Official Title
Effect of Antimicrobial Treatment of Acute Otitis Media on the Intestinal Microbiome in Children: A Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
November 2016 (undefined)
Primary Completion Date
March 2020 (Actual)
Study Completion Date
March 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oulu
Collaborators
Oulu University Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a randomized, controlled trial studying the effects of various antimicrobial treatments on the intestinal microbiome of small children. The participating children with acute otitis media are treated wither with amoxicillin, amoxicillin-clavulanate or without antibiotics. The children with allergy to amoxicillin receive a course of macrolide and they will be monitored as a separate group. The main outcomes of this trial are the changes in the intestinal microbiome after the treatment.
Detailed Description
Antimicrobial treatment of acute otitis media has been proven efficacious in children. It has been suggested that antimicrobial treatment makes a lot of harm to intestinal microbiome and may thus have effects on the child's health and wellbeing. However, data on these changes and their magnitude is scanty. This is a randomized, controlled trial studying the effects of various antimicrobial treatments on the intestinal microbiome of small children. The participating children with acute otitis media are treated wither with amoxicillin, amoxicillin-clavulanate or without antibiotics. The children with allergy to amoxicillin receive a course of macrolide and they will be monitored as a separate group. The main outcomes of this trial are the changes in the intestinal microbiome after the treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Otitis Media
Keywords
children, intestinal microbiome, microbiota, antimicrobial course, amoxicillin, amoxicillin-clavulanate, macrolide

7. Study Design

Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
73 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Amoxicillin
Arm Type
Active Comparator
Arm Description
The children with acute otitis media will be treated with amoxicillin mixture, 100mg/ml, 40mg/kg/d, divided to two daily doses for 7 days.
Arm Title
Amoxicillin-Potassium Clavulanate
Arm Type
Active Comparator
Arm Description
The children with acute otitis media will be treated with amoxicillin-clavulanate mixture, 80mg/ml, 45mg/kg/d, divided to two daily doses for 7 days.
Arm Title
Wait and see
Arm Type
No Intervention
Arm Description
The children with acute otitis media will be monitored without antimicrobial treatment.
Arm Title
Macrolide
Arm Type
Other
Arm Description
The children with acute otitis media with known allergy to amoxicillin or amoxicillin-clavulanate will be treated with macrolide and monitored as a separate group, outside randomization.
Intervention Type
Drug
Intervention Name(s)
Amoxicillin
Intervention Description
The children with acute otitis media will be treated with amoxixillin mixture, 100mg/ml, 40mg/kg/d, divided to two daily doses for 7 days.
Intervention Type
Drug
Intervention Name(s)
Amoxicillin-Potassium Clavulanate
Intervention Description
The children with acute otitis media will be treated with amoxixillin-clavulanate mixture, 80mg/ml, 45mg/kg/d, divided to two daily doses for 7 days.
Intervention Type
Drug
Intervention Name(s)
Macrolide
Intervention Description
The children with acute otitis media with a know allergy to amoxicillin or amoxicillin-clavulanate will be treated with macrolide and monitored separately
Primary Outcome Measure Information:
Title
Change in the relative abundance of Firmicutes in stool samples
Description
Change in the relative abundance of Firmicutes in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
Time Frame
Change from baseline to 10 days
Secondary Outcome Measure Information:
Title
Principal coordinate analysis (PCA) of fecal samples
Description
Principal coordinate analysis (PCA) of the microbiota of fecal samples 10 days after starting treatment to acute otitis media
Time Frame
10 days
Title
Change in the relative abundance of Actinobacteria in stool samples
Description
Change in the relative abundance of Actinobacteria in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
Time Frame
Change from baseline to 10 days
Title
Change in the relative abundance of Bacteroidetes in stool samples
Description
Change in the relative abundance of Bacteroidetes in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
Time Frame
Change from baseline to 10 days
Title
Change in the relative abundance of Proteobacteria in stool samples
Description
Change in the relative abundance of Proteobacteria in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
Time Frame
Change from baseline to 10 days
Title
Change in the relative abundance of Verrucomicrobia in stool samples
Description
Change in the relative abundance of Verrucomicrobia in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
Time Frame
Change from baseline to 10 days
Title
Change in the relative abundance of Lactobacilli in stool samples
Description
Change in the relative abundance of Lactobacilli in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
Time Frame
Change from baseline to 10 days
Title
Change in the relative abundance of Bifidobacteria in stool samples
Description
Change in the relative abundance of Bifidobacteria in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
Time Frame
Change from baseline to 10 days
Title
Change in the relative abundance of Faecalibacterium prausnitzii in stool samples
Description
Change in the relative abundance of Faecalibacterium prausnitzii in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
Time Frame
Change from baseline to 10 days
Title
Change in the diversity of fecal microbiota measured with the number of operational taxonomic units (OTUs)
Description
Change in the diversity of fecal microbiota measured with the number of operational taxonomic units (OTUs) from baseline to 10 days after the diagnosis of acute otitis media
Time Frame
Change from baseline to 10 days
Title
Change in the diversity of fecal microbiota measured with Shannon index
Description
Change in the diversity of fecal microbiota measured with Shannon index from baseline to 10 days after the diagnosis of acute otitis media
Time Frame
Change from baseline to 10 days
Title
Change in the diversity of fecal microbiota measured with Chao index
Description
Change in the diversity of fecal microbiota measured with Chao index from baseline to 10 days after the diagnosis of acute otitis media
Time Frame
Change from baseline to 10 days
Title
Presence of antimicrobial genes measured with the means of metagenomics
Description
Presence of antimicrobial genes measured with the means of metagenomics at 10 days after the diagnosis of acute otitis media
Time Frame
10 days
Title
Proportion of Clostridium difficile -positive fecal samples
Description
Occurrence of Clostridium difficile in fecal samples 10 days after the diagnosis of acute otitis media
Time Frame
10 days
Title
Proportion of fecal samples with Extended Spectrum Beta-Lactamase -positive strains
Description
Proportion of fecal samples with Extended Spectrum Beta-Lactamase -positive strains 10 days after the diagnosis of acute otitis media
Time Frame
10 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
7 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: acute symptoms of respiratory infection AND signs of inflammation on the tympanic membrane in otoscopy AND middle ear effusion found in pneumatic otoscopy Exclusion Criteria: Suspected or proven complication of acute otitis media (for example acute mastoiditis or perforated tympanic membrane) Severe acute otitis media: severe pain and fever > 39 degrees C Bilateral acute otitis media in a child younger than 2 years Primary or secondary immunodeficiency or Downs syndrome Impaired general condition or suspected severe bacterial infection Allergy to both amoxicillin and macrolide Acute otorrhea through tympanostomy tube Antimicrobial treatment ongoing or during previous 7 days
Facility Information:
Facility Name
Mehiläinen, private practice
City
Oulu
Country
Finland

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Effect of Antimicrobial Treatment of Acute Otitis Media on the Intestinal Microbiome in Children

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