Effects of Phenoximethylpenicillin, Amoxicillin and Amoxicillin-clavulanic Acid on the Gut Microbiota

NCT04084106 | Completed Phase 4 FDA Drug

• 1 other identifier: 2019-03300
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

The overall aim of the project is to fill an important knowledge gap on the ecological effects of selected antibiotics. The results will be used to guide treatment decisions for common infections to as much as possible reduce the negative impact on the intestinal microbiota and consequently the risks of side effect and resistance development during therapy. Specific aims for this study are to determine (1) the composition of intestinal microbiota and prevalence of resistant bacteria and resistance genes prior to and up to 1 year after antibiotic treatment, and (2) the relative effects on the microbiota after treatment with three antibiotics used for lower respiratory tract infections; phenoximethylpenicillin, amoxicillin and amoxicillin-clavulanic acid, or no treatment (control). A total of 120 healthy volunteers will be recruited to the study. They are randomised to 5 days' treatment with phenoximethylpenicillin, amoxicillin or amoxicillin-clavulanic acid, or to no antibiotic treatment. Subjects submit faecal samples at eight different time-points; at the start of the study (before treatment), immediately, one week and 1, 3, 6, 12 and 24 months after completion of the treatment. The samples will be delivered to Scilifelab for metagenomic sequencing to detect antibiotic resistant genes and analysis of the intestinal microbiota and to the Microbiology ward for analysis with phenotypic methods (culturomics) to detect resistant genes and resistant bacteria.

Conditions

Infectious Disease

Keywords

randomized trial; antibiotic resistant genes; gut microbiota; healthy volunteers; metagenomics

Outcome Measures

Primary Outcomes (6)

• Diversity of the intestinal microbiota prior to and after (any) antibiotic treatment as determined with metagenomics on repeated faecal samples.

  The diversity of the intestinal microbiota prior to and up to 2 year after antibiotic treatment will be determined by sequencing with shotgun metagenomics.

  2 year

• Comparison of the diversity of the intestinal microbiota with three different antibiotics - phenoxymethylpenicillin (reference), amoxicillin and amoxicillin-clavulanic acid - as determined with metagenomics on repeated faecal samples.

  The relative effects of on the diversity of the intestinal microbiota prior to and up to 2 year after antibiotic treatment will be determined by sequencing with shotgun metagenomics.

  2 years

• Prevalence of resistance genes in the intestinal microbiota prior to and after (any) antibiotic treatment as determined with metagenomics on repeated faecal samples.

  The prevalence of resistant bacteria and resistance genes prior to and up to 2 year after antibiotic treatment will be determined by sequencing with shotgun metagenomics.

  2 years

• Comparison of the prevalence of resistance genes in the intestinal microbiota with different antibiotics - phenoxymethylpenicillin, amoxicillin and amoxicillin-clavulanic acid - as determined with metagenomics on repeated faecal samples.

  The relative effects of on the prevalence of resistant bacteria and resistance genes prior to and up to 2 year after treatment with phenoxymethylpenicillin (reference), amoxicillin or amoxicillin-clavulanic acid will be determined by sequencing with shotgun metagenomics.

  2 years

• Prevalence of multidrug-resistant bacteria in the intestinal microbiota prior to and after (any) antibiotic treatment as determined with phenotypic analyses on repeated faecal samples.

  Multidrug-resistant gram-negative bacteria will be isolated and characterized by incubation in selective media, MIC determination using conventional methods and PCR/whole-genome sequencing to determine the presence of resistance genes.

  2 years

• Comparison of the prevalence of resistant bacteria in the intestinal microbiota with three different antibiotics - phenoxymethylpenicillin, amoxicillin and amoxicillin-clavulanic acid - as determined with phenotypic analyses on repeated faecal samples.

  Multidrug-resistant gram-negative bacteria producing will be isolated and characterized by incubation in selective media, MIC determination using conventional methods and PCR/whole-genome sequencing to determine the presence of resistance genes.

  2 years

Secondary Outcomes (2)

• Prevalence of adverse events with (any) antibiotic treatment.

  1 year

• Comparison of prevalence of adverse events with three different antibiotics - phenoxymethylpenicillin (reference), amoxicillin and amoxicillin-clavulanic acid.

  1 year

Study Arms (4)

phenoximethylpenicillin

EXPERIMENTAL

phenoximethylpenicillin, tablet, 1 g 3 times daily for 5 days.

Drug: Phenoxymethylpenicillin

amoxicillin

ACTIVE COMPARATOR

amoxicillin, tablet, 500 mg 3 times daily for 5 days.

Drug: Amoxicillin

amoxicillin-clavulanic acid

ACTIVE COMPARATOR

amoxicillin-clavulanic acid tablet, 500/125 mg 3 times daily for 5 days.

Drug: Amoxicillin-clavulanic acid

No intervention

NO INTERVENTION

No intervention

Interventions

Phenoxymethylpenicillin DRUG

Oral administration

phenoximethylpenicillin

Amoxicillin DRUG

Oral administration

amoxicillin

Amoxicillin-clavulanic acid DRUG

Oral administration

amoxicillin-clavulanic acid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• Age ≥ 18 years

You may not qualify if:

• Chronic disease, allergy, asthma, recurrent infections
• Ongoing antibiotic treatment
• Antibiotic treatment the past 12 months
• Pregnancy or planned pregnancy within the study period
• Known allergy to phenoximethylpenicillin, amoxicillin and amoxicillin- clavulanic acid

Sponsors & Collaborators

• Uppsala University: lead

Study Sites (1)

Uppsala University Hospital

Uppsala, Sweden

Location

MeSH Terms

Conditions

Communicable Diseases

Interventions

Penicillin V; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ampicillin; Penicillin G; Clavulanic Acid; Clavulanic Acids; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Thomas Tängdén, MD, PhD

  Uppsala University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Model Details: Randomized clinical trail

Study Record Dates

• First Submitted: August 30, 2019
• First Posted: September 10, 2019
• Study Start: September 10, 2019
• Primary Completion: November 11, 2022
• Study Completion: November 11, 2022
• Last Updated: December 2, 2022

Record last verified: 2022-12

Locations

SE (1)