Escherichia Coli Bloodstream InfectionSEPTICOLINCT02890901
Prognostic Factors of Escherichia Coli Bloodstream Infections: Severity Score and Therapeutic Implications
An observational study of Escherichia Coli Bloodstream Infection, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The determinants associated with severe outcome and death from Escherichia coli bloodstream infections (BSI) remain poorly understood. The epidemiology of E. coli BSI has recently changed dramatically with the global emergence of multiresistant strains producing extended-spectrum ß-lactamases (ESBL). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Escherichia Coli Bloodstream Infection
- How many people
- 553 participants
- Where
- 1 siteFrance
- Study dates
- 13 Oct 2016to 25 May 2018
- 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: Patients with Escherichia coli bloostream infection
Who may be able to join
- Isolation of E. coli from 1 or more set of aseptically inoculated blood culture bottle collected in one of the study centres
- Age ≥ 18 year-old
Who cannot join
- Receiving vasopressors before the onset of the bacteraemia
- Patient previously included in the study
- Patient's opposition
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prognostic Factors of Escherichia Coli Bloodstream Infections in the Face of Emerging Multi-resistance, Severity Score and Therapeutic Implications
The determinants associated with severe outcome and death from Escherichia coli bloodstream infections (BSI) remain poorly understood. The epidemiology of E. coli BSI has recently changed dramatically with the global emergence of multiresistant strains producing extended-spectrum ß-lactamases (ESBL). Outcome is worse in case of ESBL-E. coli, which may be due to the intrinsic virulence of ESBL-E. coli or to a delayed adequate empirical antibiotic therapy because of multiresistance. Predicting the severity of an infection as soon as the initial clinical assessment is of major importance to provide the best care, while limiting unnecessary hospitalizations and costs. Yet, no simple clinical score exists to predict the severity of E. coli infections.
In a translational approach, the investigators will include during a maximum of one year 500 adults with E. coli BSI hospitalized in 7 hospitals in the Paris area, France. Precise clinical data will be collected at inclusion and 28 days after inclusion or upon patient's discharge (if before day 28). The primary endpoint of the study is death from E. coli BSI at day 28.
The first aim is to determine risk-factors for death at day 28, including clinical and bacteriological factors (determined by WGS) in the era of the global emergence of ESBL producing E. coli. The second aim is to determine virulence characteristics of ESBL strains both at the genome and phenotypic level thanks to a mouse model of septicaemia, and compare them to the clinical data. The third aim, will establish and evaluate a simple clinical severity score (named COLISCORE), in order to help clinician evaluate patients' severity upon initial clinical evaluation and particularly to detect patients at risk of severe outcome. The ultimate goal of this work is to have a clinical impact on patients' management, by understanding the determinants of patient severity due to E. coli BSI in the context of current major epidemiological changes.
Read the detailed description
This project will be conducted as a collaboration between the ASSISTANCE PUBLIQUE HOPITAUX DE PARIS (or Paris teaching hospitals) and the Infection, Antimicrobials, Modelling and Evolution (IAME) research group, a joint appointment from Paris DIDEROT University, Paris Nord University and the INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM).
This study is a prospective multicentric non interventional observational, study, which will include up to 500 patients from 7 hospitals.
Study Centres:
Seven hospitals affiliated with the IAME research group and included in the ASSISTANCE PUBLIQUE HOPITAUX DE PARIS network will participate. The seven hospitals are all tertiary care teaching hospitals from Paris or the close suburbs, part of the ASSISTANCE PUBLIQUE HOPITAUX DE PARIS network. They account for a total of 4230 acute-care adult beds. A total of 780 E. coli BSI occurred in these centres in 1 year with 15% of ESBL producing strains.
This study will include adult patients hospitalized in one of the seven participating centres based on the inclusion and exclusion criteria listed below. A total of 14 clinical investigators (CI) and microbiology investigators (MI) will be responsible for patients' inclusion and data collection in each of the 7 study centres.
Visits.
Two visits will be organised:
Visit 1: day of the patient's inclusion in the study (=day of the results of the first positive blood culture)
Visit 2 : day the patient leaves the hospital or day 28 after Visit 1 if they are still hospitalized.
At visit 1, the E. coli strain responsible for the BSI as well as any other positive sample will be conserved and sent to a central laboratory for full genome sequencing of the E. coli strains (IAME Laboratory, University Paris DIDEROT). The investigators will analyze the molecular characteristics of strains using high-throughput sequencing techniques to try to highlight virulence factors and will compare the results with clinical data.
Endpoints
The primary endpoint of this work is death at day 28 (or visit 2).
Multiple secondary endpoints will be studied at day 28 including length of hospital stay and the need for intensive care.
Statistics
For the primary endpoint the investigators will analyse the risk factors associated to death at day 28 (yes/no) using logistic regression. The clinical risk factors achieving a P value < 0.10 will then be entered into the multivariate logistic regression model. A backward selection method will be used to obtain a model in which all clinical risk factors have a P value < 0.05. Second, the link between death and various bacteriological factors will be studied using a similar approach. Third, a final multivariate logistic regression will be performed adding bacterial factors to the final model with clinical risk factors and performing a backward analysis. The investigators will also perform an exploratory analysis to study the association between all the E. coli genes and death, in a model adjusted with the important clinical factors as defined above.
The investigators will use the results from the multivariate analysis to elaborate a clinical severity score for E. coli BSI, called the COLISCORE. The objective of the COLISCORE is to predict the patients' severity and outcome upon admission and help the clinician's initial management decisions. This score should be simple and easy to use at the patients' bedside.
- Conditions
- Escherichia Coli Bloodstream Infection
- Keywords
- Escherichia coli, Bloodstream infections, Severity, Score, Host factors, Microbiology
- Medical subject headings
- Escherichia coli Infections, Sepsis
What is being measured
The primary outcome is the main question the study is designed to answer.
Death
Measured: day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2016 (estimated)
- Study start13 Oct 2016
- Primary completion30 Sep 2017
- Study completion25 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Escherichia Coli Bloodstream InfectionStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- 553 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- victoire De Lastours, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02890901
- Sponsor's protocol ID
- PRTS1511
- Acronym
- SEPTICOLI
- Status last verified
- Nov 2017
- First submitted
- 1 Sep 2016
- Last updated
- 29 May 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Royer G, Darty MM, Clermont O, Condamine B, Laouenan C, Decousser JW, Vallenet D, Lefort A, de Lastours V, Denamur E; COLIBAFI and SEPTICOLI groups. Phylogroup stability contrasts with high within sequence type complex dynamics of Escherichia coli bloodstream infection isolates over a 12-year period. Genome Med. 2021 May 5;13(1):77. doi: 10.1186/s13073-021-00892-0.
PubMed 33952335de Lastours V, Laouenan C, Royer G, Carbonnelle E, Lepeule R, Esposito-Farese M, Clermont O, Duval X, Fantin B, Mentre F, Decousser JW, Denamur E, Lefort A. Mortality in Escherichia coli bloodstream infections: antibiotic resistance still does not make it. J Antimicrob Chemother. 2020 Aug 1;75(8):2334-2343. doi: 10.1093/jac/dkaa161.
PubMed 32417924
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prognostic Factors of Escherichia Coli Bloodstream Infections in the Face of Emerging Multi-resistance, Severity Score and Therapeutic Implications
- ClinicalTrials.gov ID
- NCT02890901
- Acronym / sponsor ID
- SEPTICOLI / PRTS1511
- Conditions
- Escherichia Coli Bloodstream Infection
- Keywords
- Escherichia coli, Bloodstream infections, Severity, Score, Host factors, Microbiology
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 553 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 13 Oct 2016 (actual)
- Primary completion
- 30 Sep 2017 (actual)
- Study completion
- 25 May 2018 (actual)
- First posted
- 7 Sep 2016 (estimated)
- 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.
The determinants associated with severe outcome and death from Escherichia coli bloodstream infections (BSI) remain poorly understood. The epidemiology of E. coli BSI has recently changed dramatically with the global emergence of multiresistant strains producing extended-spectrum ß-lactamases (ESBL). Outcome is worse in case of ESBL-E. coli, which may be due to the intrinsic virulence of ESBL-E. coli or to a delayed adequate empirical antibiotic therapy because of multiresistance. Predicting the severity of an infection as soon as the initial clinical assessment is of major importance to provide the best care, while limiting unnecessary hospitalizations and costs. Yet, no simple clinical score exists to predict the severity of E. coli infections.
In a translational approach, the investigators will include during a maximum of one year 500 adults with E. coli BSI hospitalized in 7 hospitals in the Paris area, France. Precise clinical data will be collected at inclusion and 28 days after inclusion or upon patient's discharge (if before day 28). The primary endpoint of the study is death from E. coli BSI at day 28.
The first aim is to determine risk-factors for death at day 28, including clinical and bacteriological factors (determined by WGS) in the era of the global emergence of ESBL producing E. coli. The second aim is to determine virulence characteristics of ESBL strains both at the genome and phenotypic level thanks to a mouse model of septicaemia, and compare them to the clinical data. The third aim, will establish and evaluate a simple clinical severity score (named COLISCORE), in order to help clinician evaluate patients' severity upon initial clinical evaluation and particularly to detect patients at risk of severe outcome. The ultimate goal of this work is to have a clinical impact on patients' management, by understanding the determinants of patient severity due to E. coli BSI in the context of current major epidemiological changes.
Detailed description
This project will be conducted as a collaboration between the ASSISTANCE PUBLIQUE HOPITAUX DE PARIS (or Paris teaching hospitals) and the Infection, Antimicrobials, Modelling and Evolution (IAME) research group, a joint appointment from Paris DIDEROT University, Paris Nord University and the INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM).
This study is a prospective multicentric non interventional observational, study, which will include up to 500 patients from 7 hospitals.
Study Centres:
Seven hospitals affiliated with the IAME research group and included in the ASSISTANCE PUBLIQUE HOPITAUX DE PARIS network will participate. The seven hospitals are all tertiary care teaching hospitals from Paris or the close suburbs, part of the ASSISTANCE PUBLIQUE HOPITAUX DE PARIS network. They account for a total of 4230 acute-care adult beds. A total of 780 E. coli BSI occurred in these centres in 1 year with 15% of ESBL producing strains.
This study will include adult patients hospitalized in one of the seven participating centres based on the inclusion and exclusion criteria listed below. A total of 14 clinical investigators (CI) and microbiology investigators (MI) will be responsible for patients' inclusion and data collection in each of the 7 study centres.
Visits.
Two visits will be organised:
Visit 1: day of the patient's inclusion in the study (=day of the results of the first positive blood culture)
Visit 2 : day the patient leaves the hospital or day 28 after Visit 1 if they are still hospitalized.
At visit 1, the E. coli strain responsible for the BSI as well as any other positive sample will be conserved and sent to a central laboratory for full genome sequencing of the E. coli strains (IAME Laboratory, University Paris DIDEROT). The investigators will analyze the molecular characteristics of strains using high-throughput sequencing techniques to try to highlight virulence factors and will compare the results with clinical data.
Endpoints
The primary endpoint of this work is death at day 28 (or visit 2).
Multiple secondary endpoints will be studied at day 28 including length of hospital stay and the need for intensive care.
Statistics
For the primary endpoint the investigators will analyse the risk factors associated to death at day 28 (yes/no) using logistic regression. The clinical risk factors achieving a P value < 0.10 will then be entered into the multivariate logistic regression model. A backward selection method will be used to obtain a model in which all clinical risk factors have a P value < 0.05. Second, the link between death and various bacteriological factors will be studied using a similar approach. Third, a final multivariate logistic regression will be performed adding bacterial factors to the final model with clinical risk factors and performing a backward analysis. The investigators will also perform an exploratory analysis to study the association between all the E. coli genes and death, in a model adjusted with the important clinical factors as defined above.
The investigators will use the results from the multivariate analysis to elaborate a clinical severity score for E. coli BSI, called the COLISCORE. The objective of the COLISCORE is to predict the patients' severity and outcome upon admission and help the clinician's initial management decisions. This score should be simple and easy to use at the patients' bedside.
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
- Patients with Escherichia coli bloostream infection
Key inclusion criteria (2 listed)
- Isolation of E. coli from 1 or more set of aseptically inoculated blood culture bottle collected in one of the study centres
- Age ≥ 18 year-old
Key exclusion criteria (3 listed)
- Receiving vasopressors before the onset of the bacteraemia
- Patient previously included in the study
- Patient's opposition
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
Death
Time frame: day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2018.
- Derived from this study: PubMed 33952335Royer G, Darty MM, Clermont O, Condamine B, Laouenan C, Decousser JW, Vallenet D, Lefort A, de Lastours V, Denamur E; COLIBAFI and SEPTICOLI groups. Phylogroup stability contrasts with high within sequence type complex dynamics of Escherichia coli bloodstream infection isolates over a 12-year period. Genome Med. 2021 May 5;13(1):77. doi: 10.1186/s13073-021-00892-0.
- Derived from this study: PubMed 32417924de Lastours V, Laouenan C, Royer G, Carbonnelle E, Lepeule R, Esposito-Farese M, Clermont O, Duval X, Fantin B, Mentre F, Decousser JW, Denamur E, Lefort A. Mortality in Escherichia coli bloodstream infections: antibiotic resistance still does not make it. J Antimicrob Chemother. 2020 Aug 1;75(8):2334-2343. doi: 10.1093/jac/dkaa161.
- Individual participant dataSharing planned: Undecided
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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.
victoire De Lastours principal investigator
Assistance Publique - Hôpitaux de Paris
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 Escherichia Coli Bloodstream Infection, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 2 inclusion and 3 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: finished, as of the sponsor's last update on 29 May 2018. 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 France. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Death (time frame: day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02890901, which also lists 2 linked publications.
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 29 May 2018.