Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04084106
Other study ID # 2019-03300
Secondary ID
Status Completed
Phase Phase 4
First received
Last updated
Start date September 10, 2019
Est. completion date November 11, 2022

Study information

Verified date December 2022
Source Uppsala University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

Background: The rationale behind this project is that different antibiotics have varying effects on the intestinal microbiota, which has clinical implications. To investigate the relative collateral damage during treatment with different antibiotics a randomized trial is needed. Repeated sampling during a 1-year period is required to capture prolonged disturbance and the time to a restored microbiota. To readily examine the antibiotic effects healthy volunteers are ideal for the study as their microbiota is most likely to be normal at inclusion. They also have a low risk of encountering other factors during follow-up that will affect the composition of the intestinal bacteria. Aim: The purpose of the study is to determine: (1) composition of intestinal microbiota and prevalence of resistant bacteria and resistance genes prior to and up to 1 year after antibiotic treatment, and (2) differences in the microbiota after treatment with antibiotics; phenoximethylpenicillin, amoxicillin and amoxicillin-clavulanic acid respectively compared to no treatment. Method: The study is a conducted within the Department of Infectious Diseases at Uppsala University Hospital. 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. Altogether, the subjects will provide 8 faecal samples during the course of the study. A total of 960 faecal samples will be collected and analysed. Each subject will submit two faecal samples at each time-point. One sample will be frozen in DNA-shield and delivered to Scilifelab for analysis of the intestinal microbiota and metagenomic sequencing to detect antibiotic resistant genes.The other faecal sample will be delivered to the Microbiology department for analysis with phenotypic methods (culturomics) to detect resistant genes and resistant bacteria. Statistics: The compilation of data and statistics will primarily be descriptive. We will analyse the intestinal microbiota and the prevalence of resistance genes in the subjects prior to and immediately after antibiotic treatment, and then monitor the composition (diversity) of the intestinal microbiota, resistant bacteria and resistance genes 1 week, 1, 3, 6, 12 and 24 months after completion of the treatment. Diversity will be analysed using metagenomics (shotgun) and is used as a variable to compare the degree of collateral damage on the intestinal microbiota with different antibiotics, and to compare the intestinal microbiota before and after antibiotic treatment in the same individual. The diversity of the intestinal microbiota in faecal sample 1 will constitute the baseline. Targeted statistical calculations on differences between treatment groups and gender as regards intestinal microbiota, resistance and side effects will be carried out depending on outcomes, which cannot be predicted in advance. Endpoints and outcomes: The primary endpoint is the diversity and composition of the intestinal microbiota, the prevalence of multidrug-resistant Gram-negative bacteria in screening cultures and the prevalence of antibiotic resistance genes in faeces prior to and up to 2 year after antibiotic treatment. The results may be used as a basis for targeting the choice of antibiotic for pulmonary infections (pneumonia) towards those antibiotics that have the least risk of disrupting the intestinal microbiota and leading to resistance.


Recruitment information / eligibility

Status Completed
Enrollment 104
Est. completion date November 11, 2022
Est. primary completion date November 11, 2022
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Signed written informed consent - Age = 18 years Exclusion Criteria: - 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 - Planned travel outside Europe within one year from inclusion

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Phenoxymethylpenicillin
Oral administration
Amoxicillin
Oral administration
Amoxicillin-clavulanic acid
Oral administration

Locations

Country Name City State
Sweden Uppsala University Hospital Uppsala

Sponsors (1)

Lead Sponsor Collaborator
Uppsala University

Country where clinical trial is conducted

Sweden, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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 Prevalence of adverse events with (any) antibiotic treatment. Information on side effects during and following antibiotic treatment will be collected using diaries and questionnaires. 1 year
Secondary Comparison of prevalence of adverse events with three different antibiotics - phenoxymethylpenicillin (reference), amoxicillin and amoxicillin-clavulanic acid. Information on side effects during and following antibiotic treatment will be collected using diaries and questionnaires. 1 year
See also
  Status Clinical Trial Phase
Recruiting NCT05568953 - An Experimental Medicine Decipher of a Minimum Correlate of Cellular Immunity Phase 2
Completed NCT04568889 - Minnesota COVID-19 Testing Project N/A
Completed NCT06063330 - Clinical Trial to Evaluate the Safety of RQ-01 in SARS-CoV-2 Positive Subjects Phase 1
Completed NCT01198925 - Assessment of the Optimal Dosing of Piperacillin-tazobactam in Intensive Care Unit Patients: Extended Versus Continuous Infusion Phase 4
Completed NCT05063812 - Performance of a Remote Monitoring Program for Patients Diagnosed With COVID-19
Not yet recruiting NCT03636711 - Antibiotic Stewardship in Infectious Disease Departement
Completed NCT03457688 - Effect of Prebiotic Fructans to Reduce Number of Febrile Infections in Children N/A
Completed NCT03241355 - Prebiotic Fructans on the Incidence of Acute Infectious Diseases in Children N/A
Terminated NCT05420077 - Safety and Immunogenicity of RVM-V001 in Healthy Individuals Previously Vaccinated With BNT162b2 and mRNA-1273 Phase 1
Recruiting NCT05013944 - AnovaOS Network Powered Patient Registry
Completed NCT03893279 - Perception of Smell and Taste During Antibiotic Treatment
Active, not recruiting NCT05619770 - Study to Evaluate Pharmacokinetics, Safety & Tolerability of 101-PGC-005 in Healthy, Adult, Human Subjects Phase 1
Completed NCT01772901 - Brief Influenza Vaccine Education to Pregnant Women N/A
Completed NCT05413772 - Temocillin in ESBL-Enterobacteriaceae Infections
Completed NCT04319328 - Is Cefazolin, Ceftazidime and Ciprofloxacin Dosing Optimal in Hemodialysis Patients?
Completed NCT04613271 - Efficacy and Safety of Favipiravir in Covid-19 Patients in Indonesia Phase 3
Completed NCT03239665 - Vaccination Education Through Pharmacists and Senior Centers (VEPSC) N/A
Completed NCT03224026 - Validation of a Proteomic Signature and Assessment of Viremia in Children With Fever Without Source
Not yet recruiting NCT06102070 - Genetic Susceptibility to Severe Infections
Recruiting NCT04339179 - Observational Research on Infectious Disease Outbreaks and Difficult Cases of Unidentified Etiology in Indonesia