Patients at High Risk of Antibacterial Treatment Upon AdmissionPILGRIMNCT03765528
Impact of Prescription Quality, Infection Control and Antimicrobial Stewardship on Gut Microbiota Domination by Healthcare-Associated Pathogens
An observational study of Patients at High Risk of Antibacterial Treatment Upon Admission, run by University Hospital of Cologne at 1 site in Germany.
Trial summary
Extended-spectrum beta-lactamase producing Enterobacteriaceae (EPE), vancomycin-resistant enterococci (VRE) and Clostridium difficile have become a major threat to hospitalised patients worldwide. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Patients at High Risk of Antibacterial Treatment Upon Admission
- How many people
- 1,500 participants
- Where
- 1 siteGermany
- Study dates
- 1 Jan 2019to 31 Jul 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Hospitalized patients at high risk of receiving antibiotic treatment during their hospital stay will be screened for study eligibility.
Who may be able to join
- Age ≥ 18 years
- Planned treatment or high likelihood of any systemic antibacterial treatment except trimethoprim/sulfamethoxazole within the next 10 days for a duration of ≥ 5 days
- Patients able to provide a stool sample before or within 4 hours of receiving first antibiotic dosage
- Written informed consent provided prior to inclusion
Who cannot join
- Patients who have received courses of systemic antibacterials for 7 days or more within the past two months
- Patients having received any antibacterial compound other than trimethoprim/sulfamethoxazole within 14 days prior to study enrolment except first antibiotic dosage within 4 hours prior enrolment
- Patients with diarrhea at enrolment (≥3 unformed bowel movements within 24h)
- Patients with a stoma (jejunostomy, ileostomy, or colostomy) at time of inclusion
- Patients on enteral (tube fed or PEG) or parenteral nutrition
- Patient with any social or logistical condition which in the opinion of the investigator may interfere with the conduct of the study, such as incapacity to well understand, not willing to collaborate, or cannot easily be contacted after discharge
- Patients exclusively treated as outpatients without prior hospital admission
- Previous participation in this study
Trial locations and contacts
1 site in 1 country.
Annika Löhnert, MD contact
Germany1 site, 1 recruiting
- Recruiting
University Hospital of Cologne
Cologne, North Rhine-Westphalia, 50931
Jörg Janne Vehreschild, MD, joerg.vehreschild@uk-koeln.de
About this study
Extended-spectrum beta-lactamase producing Enterobacteriaceae (EPE), vancomycin-resistant enterococci (VRE) and Clostridium difficile have become a major threat to hospitalised patients worldwide. We hypothesize that receiving inappropriate antibacterial treatment places patients at high risk of intestinal domination and subsequent infection by these bacteria. Further analyses will address cost-effectiveness of specific interventions, behavioural analyses of the decision process leading to inappropriate antibacterial treatment, and the rate of undetected colonization with EPE/VRE/C. difficile on admission.
Read the detailed description
The prevalence of antimicrobial resistant pathogens has dramatically increased among hospitalised patients worldwide. While various management strategies have effectively reduced the burden caused by methicillin-resistant Staphylococcus aureus, resistant pathogens with a preference towards intestinal colonization are currently on the rise. E.g., vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase producing Enterobacteriaceae (EPE) now constitute a significant threat to hospitalised patients worldwide, as infections due to these organisms require prolonged treatments and result in inferior outcomes. Similarly, the burden of disease caused by Clostridium difficile infection (CDI), the main cause of healthcare-associated infectious diarrhoea, has increased driven by the emergence of hypervirulent strains such as ribotypes 027 and 078. Molecular studies have demonstrated that increased population-wide exposure to broad-spectrum antibacterials is a crucial step in the initiation of outbreaks by selection and expansion of resistant C. difficile.
This is a comprehensive, multinational, multi-centre clinical study aiming to assess the impact of inappropriate antibacterial prescription on intestinal domination by EPE or VRE or infection with C. difficile. To achieve this goal, the study will closely follow the progression from first acquisition of drug-resistant organisms to infection with these bacteria at an individual patient level.
In this study, we will establish the sequence and factors involved in acquisition, colonization, selective pressure, bacterial overgrowth/domination/ and infection for EPE, VRE and C. difficile. We hypothesize that IC (Infection Control; prevention of pathogen acquisition) and AMS (Antimicrobial Stewardship; prevention of clonal expansion) measures leading to a higher share of appropriate anti-infective use are effective strategies to prevent this development. The study programme will allow an accurate estimation of the preventable share of healthcare-acquired colonization and infection by VRE, EPE, and C. difficile.
No direct interventions will be performed with study patients. Instead, study centres will assess quality indicators for implementation of IC and AMS measures by active observation and aggregation of data. Patients fulfilling all inclusion- and no exclusion criteria will be asked for their consent to be recruited prospectively into a cohort study. During the observational phase, participants will be monitored for receipt of antibacterial treatment and regular stool samples will be obtained and stored. An interdisciplinary, international AMS Board will comprehensively assess antibiotic treatment via review by a panel of experts. After the observation is completed, stool samples will be batch-tested for intestinal domination by the target pathogens of this study. Statistical analyses will be performed to investigate an association between inappropriate antibiotic use as opposed to appropriate or no antibiotic use and intestinal domination. If domination is detected, further analyses for phenotype, quantity, resistance, and molecular biology will be performed. Finally, the baseline sample will be tested for presence of the dominant species to understand the source of the pathogen, i.e. nosocomial versus outpatient acquisition.
- Keywords
- Clostridium difficile, Extended-Spectrum β-Lactamase producing Enterobacteriaceae, Vancomycin-resistant enterococci, Antimicrobial resistance, Microbiome, Nosocomial infection, Antimicrobial Stewardship, Infection Control
- Medical subject headings
- Cross Infection
What is being measured
The primary outcome is the main question the study is designed to answer.
Impact of inappropriate antibacterial prescription on intestinal microbiota domination by healthcare associated pathogens
The differential impact of inappropriate antibacterial prescription compared to adequate or no antibacterial prescription on intestinal microbiota domination by EPE or VRE or infection with C. difficile measured by analysing stool samples.
Measured: up to 6 - 36 weeks
Secondary outcomes (6)
Time-point of Intestinal Colonization
Determination of the rate of in-hospital vs. pre-admission intestinal colonization with EPE, VRE, and/or C. difficile measured by analysing stool samples.
Measured: Baseline and up to 6 - 36 weeks
Time-point of Intestinal Domination
Determination of the rate of in-hospital vs. pre-admission intestinal domination with EPE, VRE, and/or C. difficile measured by analysing stool samples.
Measured: Baseline and up to 6 - 36 weeks
Inter-rater reliability of AMS specialists
Determination of the inter-rater reliability of interdisciplinary AMS specialists rating antibacterial prescription appropriateness.
Measured: After complete documentation of each patient case (follow-up for 6-36 weeks) followed by completed ratings of AMS specialists
Rationale for antibacterial prescription habits assessed by performing qualitative interviews with prescribing physicians
Identification of behavioral determinants and knowledge gaps leading to inappropriate antibacterial prescriptions by interviewing approximately 50 prescribing physicians.
Measured: After complete documentation of patient case (follow-up for 6-36 weeks) through study completion
Correlation of prescription and AMS implementation
Assessment of the correlation of appropriate antibacterial prescription with quality indicators of AMS implementation
Measured: Baseline, 12 months, 24 months
Identification of risk factors responsible for disrupting the intestinal microbiota
Identification of risk factors for colonization, intestinal domination, and infection by EPE, VRE and C. difficile, including comorbidities and drugs known to disrupt the intestinal microbiota, and high-risk bacterial clones prone to dominate the microbiota due to high fitness. Assessment by analysing stool samples and documented data.
Measured: Baseline and weekly up to 6 - 36 weeks of follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2018
- Study start1 Jan 2019
- Primary completion31 Jul 2021 (estimated)
- Study completion31 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Patients at High Risk of Antibacterial Treatment Upon AdmissionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital of Cologne
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital of North Norway, Karolinska Institutet, Rabin Medical Center, University of Latvia, McGill University Health Centre/Research Institute of the McGill University Health Centre, Haukeland University Hospital, University Hospital, Akershus, Helse Stavanger HF, Goethe University
- Responsible party
- Principal investigator, Dr. med. Jörg Janne Vehreschild, University Hospital of Cologne
- Investigators
- Jörg Janne Vehreschild, MD, Principal investigator, University Hospital of Cologne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03765528
- Sponsor's protocol ID
- PILGRIM
- Acronym
- PILGRIM
- Status last verified
- Jul 2020
- First submitted
- 16 Nov 2018
- Last updated
- 3 Aug 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Prescription Quality, Infection Control and Antimicrobial Stewardship on Gut Microbiota Domination by Healthcare-Associated Pathogens
- ClinicalTrials.gov ID
- NCT03765528
- Acronym / sponsor ID
- PILGRIM / PILGRIM
- Keywords
- Clostridium difficile, Extended-Spectrum β-Lactamase producing Enterobacteriaceae, Vancomycin-resistant enterococci, Antimicrobial resistance, Microbiome, Nosocomial infection, Antimicrobial Stewardship, Infection Control
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,500 participants (estimated)
- Lead sponsor
- University Hospital of CologneUniversity, hospital or other
- Collaborators
- University Hospital of North Norway, Karolinska Institutet, Rabin Medical Center, University of Latvia, McGill University Health Centre/Research Institute of the McGill University Health Centre, Haukeland University Hospital, University Hospital, Akershus, Helse Stavanger HF, Goethe University
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 31 Jul 2021 (estimated)
- Study completion
- 31 Jul 2022 (estimated)
- First posted
- 5 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Extended-spectrum beta-lactamase producing Enterobacteriaceae (EPE), vancomycin-resistant enterococci (VRE) and Clostridium difficile have become a major threat to hospitalised patients worldwide. We hypothesize that receiving inappropriate antibacterial treatment places patients at high risk of intestinal domination and subsequent infection by these bacteria. Further analyses will address cost-effectiveness of specific interventions, behavioural analyses of the decision process leading to inappropriate antibacterial treatment, and the rate of undetected colonization with EPE/VRE/C. difficile on admission.
Detailed description
The prevalence of antimicrobial resistant pathogens has dramatically increased among hospitalised patients worldwide. While various management strategies have effectively reduced the burden caused by methicillin-resistant Staphylococcus aureus, resistant pathogens with a preference towards intestinal colonization are currently on the rise. E.g., vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase producing Enterobacteriaceae (EPE) now constitute a significant threat to hospitalised patients worldwide, as infections due to these organisms require prolonged treatments and result in inferior outcomes. Similarly, the burden of disease caused by Clostridium difficile infection (CDI), the main cause of healthcare-associated infectious diarrhoea, has increased driven by the emergence of hypervirulent strains such as ribotypes 027 and 078. Molecular studies have demonstrated that increased population-wide exposure to broad-spectrum antibacterials is a crucial step in the initiation of outbreaks by selection and expansion of resistant C. difficile.
This is a comprehensive, multinational, multi-centre clinical study aiming to assess the impact of inappropriate antibacterial prescription on intestinal domination by EPE or VRE or infection with C. difficile. To achieve this goal, the study will closely follow the progression from first acquisition of drug-resistant organisms to infection with these bacteria at an individual patient level.
In this study, we will establish the sequence and factors involved in acquisition, colonization, selective pressure, bacterial overgrowth/domination/ and infection for EPE, VRE and C. difficile. We hypothesize that IC (Infection Control; prevention of pathogen acquisition) and AMS (Antimicrobial Stewardship; prevention of clonal expansion) measures leading to a higher share of appropriate anti-infective use are effective strategies to prevent this development. The study programme will allow an accurate estimation of the preventable share of healthcare-acquired colonization and infection by VRE, EPE, and C. difficile.
No direct interventions will be performed with study patients. Instead, study centres will assess quality indicators for implementation of IC and AMS measures by active observation and aggregation of data. Patients fulfilling all inclusion- and no exclusion criteria will be asked for their consent to be recruited prospectively into a cohort study. During the observational phase, participants will be monitored for receipt of antibacterial treatment and regular stool samples will be obtained and stored. An interdisciplinary, international AMS Board will comprehensively assess antibiotic treatment via review by a panel of experts. After the observation is completed, stool samples will be batch-tested for intestinal domination by the target pathogens of this study. Statistical analyses will be performed to investigate an association between inappropriate antibiotic use as opposed to appropriate or no antibiotic use and intestinal domination. If domination is detected, further analyses for phenotype, quantity, resistance, and molecular biology will be performed. Finally, the baseline sample will be tested for presence of the dominant species to understand the source of the pathogen, i.e. nosocomial versus outpatient acquisition.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Hospitalized patients at high risk of receiving antibiotic treatment during their hospital stay will be screened for study eligibility.
Key inclusion criteria (4 listed)
- Age ≥ 18 years
- Planned treatment or high likelihood of any systemic antibacterial treatment except trimethoprim/sulfamethoxazole within the next 10 days for a duration of ≥ 5 days
- Patients able to provide a stool sample before or within 4 hours of receiving first antibiotic dosage
- Written informed consent provided prior to inclusion
Key exclusion criteria (8 listed)
- Patients who have received courses of systemic antibacterials for 7 days or more within the past two months
- Patients having received any antibacterial compound other than trimethoprim/sulfamethoxazole within 14 days prior to study enrolment except first antibiotic dosage within 4 hours prior enrolment
- Patients with diarrhea at enrolment (≥3 unformed bowel movements within 24h)
- Patients with a stoma (jejunostomy, ileostomy, or colostomy) at time of inclusion
- Patients on enteral (tube fed or PEG) or parenteral nutrition
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Impact of inappropriate antibacterial prescription on intestinal microbiota domination by healthcare associated pathogens
Time frame: up to 6 - 36 weeks
The differential impact of inappropriate antibacterial prescription compared to adequate or no antibacterial prescription on intestinal microbiota domination by EPE or VRE or infection with C. difficile measured by analysing stool samples.
6 secondary outcomes
Time-point of Intestinal Colonization
Time frame: Baseline and up to 6 - 36 weeks
Time-point of Intestinal Domination
Time frame: Baseline and up to 6 - 36 weeks
Inter-rater reliability of AMS specialists
Time frame: After complete documentation of each patient case (follow-up for 6-36 weeks) followed by completed ratings of AMS specialists
Rationale for antibacterial prescription habits assessed by performing qualitative interviews with prescribing physicians
Time frame: After complete documentation of patient case (follow-up for 6-36 weeks) through study completion
Correlation of prescription and AMS implementation
Time frame: Baseline, 12 months, 24 months
Identification of risk factors responsible for disrupting the intestinal microbiota
Time frame: Baseline and weekly up to 6 - 36 weeks of follow-up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2020.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Annika Löhnert, MD contact
Jörg Janne Vehreschild, MD principal investigator
University Hospital of Cologne
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Patients at High Risk of Antibacterial Treatment Upon Admission, run by University Hospital of Cologne at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jörg Janne Vehreschild, MD (+49227478 ext. 88794, joerg.vehreschild@uk-koeln.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Impact of inappropriate antibacterial prescription on intestinal microbiota domination by healthcare associated pathogens (time frame: up to 6 - 36 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2020.