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

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ClinicalTrials.gov Identifier: NCT02935374
Recruitment Status : Recruiting
First Posted : October 17, 2016
Last Update Posted : June 14, 2019
Sponsor:
Collaborator:
Oulu University Hospital
Information provided by (Responsible Party):
University of Oulu

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.

Condition or disease Intervention/treatment Phase
Acute Otitis Media Drug: Amoxicillin Drug: Amoxicillin-Potassium Clavulanate Drug: Macrolide Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Effect of Antimicrobial Treatment of Acute Otitis Media on the Intestinal Microbiome in Children: A Randomized Controlled Trial
Study Start Date : November 2016
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Amoxicillin
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.
Drug: Amoxicillin
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.

Active Comparator: Amoxicillin-Potassium Clavulanate
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.
Drug: Amoxicillin-Potassium Clavulanate
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.

No Intervention: Wait and see
The children with acute otitis media will be monitored without antimicrobial treatment.
Macrolide
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.
Drug: Macrolide
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 Measures :
  1. Change in the relative abundance of Firmicutes in stool samples [ Time Frame: Change from baseline to 10 days ]
    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 :
  1. Principal coordinate analysis (PCA) of fecal samples [ Time Frame: 10 days ]
    Principal coordinate analysis (PCA) of the microbiota of fecal samples 10 days after starting treatment to acute otitis media

  2. Change in the relative abundance of Actinobacteria in stool samples [ Time Frame: Change from baseline to 10 days ]
    Change in the relative abundance of Actinobacteria in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.

  3. Change in the relative abundance of Bacteroidetes in stool samples [ Time Frame: Change from baseline to 10 days ]
    Change in the relative abundance of Bacteroidetes in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.

  4. Change in the relative abundance of Proteobacteria in stool samples [ Time Frame: Change from baseline to 10 days ]
    Change in the relative abundance of Proteobacteria in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.

  5. Change in the relative abundance of Verrucomicrobia in stool samples [ Time Frame: Change from baseline to 10 days ]
    Change in the relative abundance of Verrucomicrobia in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.

  6. Change in the relative abundance of Lactobacilli in stool samples [ Time Frame: Change from baseline to 10 days ]
    Change in the relative abundance of Lactobacilli in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.

  7. Change in the relative abundance of Bifidobacteria in stool samples [ Time Frame: Change from baseline to 10 days ]
    Change in the relative abundance of Bifidobacteria in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.

  8. Change in the relative abundance of Faecalibacterium prausnitzii in stool samples [ Time Frame: Change from baseline to 10 days ]
    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.

  9. Change in the diversity of fecal microbiota measured with the number of operational taxonomic units (OTUs) [ Time Frame: Change from baseline to 10 days ]
    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

  10. Change in the diversity of fecal microbiota measured with Shannon index [ Time Frame: Change from baseline to 10 days ]
    Change in the diversity of fecal microbiota measured with Shannon index from baseline to 10 days after the diagnosis of acute otitis media

  11. Change in the diversity of fecal microbiota measured with Chao index [ Time Frame: Change from baseline to 10 days ]
    Change in the diversity of fecal microbiota measured with Chao index from baseline to 10 days after the diagnosis of acute otitis media

  12. Presence of antimicrobial genes measured with the means of metagenomics [ Time Frame: 10 days ]
    Presence of antimicrobial genes measured with the means of metagenomics at 10 days after the diagnosis of acute otitis media

  13. Proportion of Clostridium difficile -positive fecal samples [ Time Frame: 10 days ]
    Occurrence of Clostridium difficile in fecal samples 10 days after the diagnosis of acute otitis media

  14. Proportion of fecal samples with Extended Spectrum Beta-Lactamase -positive strains [ Time Frame: 10 days ]
    Proportion of fecal samples with Extended Spectrum Beta-Lactamase -positive strains 10 days after the diagnosis of acute otitis media


Other Outcome Measures:
  1. Proportion of children with diarrhea [ Time Frame: 10 days ]
    Occurrence of diarrhea after the diagnosis of acute otitis media

  2. Duration of earache [ Time Frame: 10 days ]
    Duration of earache after the diagnosis of acute otitis media



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Ages Eligible for Study:   6 Months to 7 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02935374


Contacts
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Contact: Marjo Renko, MD, Docent +358 50 387 8887 marjo.renko@oulu.fi
Contact: Terhi Tapiainen, MD, Docent +358 8 315 5185 terhi.tapiainen@oulu.fi

Locations
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Finland
Mehiläinen, private practice Recruiting
Oulu, Finland
Contact: Tero Kontriokari, MD, PhD       tero.kontiokari@mehilainen.fi   
Contact: Terhi Tapiainen, MD, PhD       terhi.tapiainen@oulu.fi   
Principal Investigator: Marjo Renko, MD, PhD         
Sub-Investigator: Terhi Tapiainen, MD, PhD         
Sponsors and Collaborators
University of Oulu
Oulu University Hospital

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Responsible Party: University of Oulu
ClinicalTrials.gov Identifier: NCT02935374     History of Changes
Other Study ID Numbers: OY20167
First Posted: October 17, 2016    Key Record Dates
Last Update Posted: June 14, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by University of Oulu:
children
intestinal microbiome
microbiota
antimicrobial course
amoxicillin
amoxicillin-clavulanate
macrolide
Additional relevant MeSH terms:
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Otitis
Otitis Media
Ear Diseases
Otorhinolaryngologic Diseases
Amoxicillin
Anti-Bacterial Agents
Clavulanic Acid
Clavulanic Acids
Amoxicillin-Potassium Clavulanate Combination
Anti-Infective Agents
beta-Lactamase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action