AzTrials
AzTrials

Enterobacteria InfectionsCOPROBLSE2NCT04699981

Can the Relative Fecal Abundance of BLSE and the Digestive Microbiota be Predictive of the Risk of Infection in a Carrier Patient?

A study testing Case (Patients colonized rectally with ESBL-producing enterobacteriaceae, with antibiotic pressure) in people with Enterobacteria Infections, run by Fondation Hôpital Saint-Joseph at 4 sites in France.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Among Enterobacteriaceae, the production of beta-lactamases (ESBLs) is the leading cause of multi-resistance. The first cases of ESBL-producing Enterobacteriaceae (E-ESBL) infections were described in the 1980s and subsequently experienced worldwide dissemination. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Enterobacteria Infections
What is being tested?
Case (Patients colonized rectally with ESBL-producing enterobacteriaceae, with antibiotic pressure)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
4 sitesFrance
Study dates
31 Mar 2022to 31 Dec 2024
Phase
Interventional
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

Who may be able to join

  • Adult patient (≥ 18 years old) hospitalized at the Paris Saint-Joseph Hospital Group or in the intensive care unit of Avicenne hospital, Necker Enfants Malades hospital, Center Sud Francilien, detected as a carrier of enterobacteriaceae in the digestive system ESBL producers
  • Patient affiliated to a health insurance plan
  • French-speaking patient
  • Patient living at home, in EHPAD or retirement home
  • Patient or Relative able to give free, informed and express consent

Who cannot join

  • Known patient colonized rectally with ESBL-producing enterobacteria and subjected to antibiotic pressure other than beta-lactams
  • Patient participating simultaneously in other intervention research that may interfere with the objectives of the study
  • Patient under guardianship or curatorship
  • Patient deprived of liberty
  • Pregnant or breastfeeding woman

Trial locations and contacts

4 sites in 1 country.

Benoit PILMIS, MD contact

144127820 ext. +33

bpilmis@ghpsj.fr

Helene BEAUSSIER, PharmD, pHD contact

144127883 ext. +33

crc@ghpsj.fr

France4 sites, 4 recruiting
  • Hôpital Avicenne

    Bobigny, 93000

    Jean-Ralph Zahar, MD, jean-ralph.zahar@aphp.fr

    Jean-Ralph Zahar, MD

    Not yet recruiting
  • Centre Hospitalier Sud-Francilien

    Corbeil-Essonnes, 91106

    Didier LECOINTE, MD, didier.lecointe@chsf.fr

    Didier LECOINTE, MD

    Not yet recruiting
  • Groupe Hospitalier Paris Saint-Joseph

    Paris, Groupe Hospitalier Paris Saint-Joseph, 75014

    Benoit PILMIS, MD, 144127820 ext. +33, bpilmis@ghpsj.fr

    Recruiting
  • Hôpital Necker-Enfants malades

    Paris, Groupe Hospitalier Paris Saint-Joseph, 75015

    Claire ROUZAUD, MD, claire.rouzaud@aphp.fr

    Claire ROUZAUD, MD

    Not yet recruiting

Other trials in France

About this study

Among Enterobacteriaceae, the production of beta-lactamases (ESBLs) is the leading cause of multi-resistance. The first cases of ESBL-producing Enterobacteriaceae (E-ESBL) infections were described in the 1980s and subsequently experienced worldwide dissemination.

Since the turn of the century, the prevalence of E-ESBL infections, especially among Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) has increased dramatically.

Read more

The emergence of multidrug-resistant Enterobacteriaceae is currently a real public health problem. The European Antimicrobial Resistance Surveillance Network evaluated, among clinical strains, the rate of resistance to 3rd generation cephalosporins (C3G) at 9.5% for E. coli and 28% for K. pneumoniae. Numerous studies have shown that bacterial colonization is the prerequisite for the occurrence of many infections.

However, the existence of prior colonization does not seem to be the only risk factor for the occurrence of a secondary infection. Therefore, in patients with multidrug-resistant Gram-negative bacillus gastrointestinal carriage there appear to be factors associated with the onset of infection. Several studies have examined the risk factors associated with E-ESBL-related infections in both community-based and healthcare-associated / nosocomial infections. Two main risk factors seem to be associated with E-ESBL infections: prior antibiotic therapy and the existence of invasive devices.

A recent study, carried out on 1288 patients and aimed at validating a predictive score for the occurrence of ESBL-E bacteremia, demonstrated 5 factors associated with the appearance of E-ESBL-linked bacteremia. These factors were: (i) a history of colonization / infection with ESBL-E, (ii) age ≥ 43 years, (iii) recent hospitalization in a region with a high prevalence of ESBL-E, (iv) antibiotic therapy ≥ 6 days in the previous 6 months and (v) the existence of a chronic vascular access.

Recently, a retrospective case-control study conducted in the United States by Augustine et al. Suggested that 5% of cases of bacteremia were related to ESBL-E.

Few studies have looked at risk factors for infection in patients known to be colonized by the digestive system. In a retrospective case-control study, conducted outside the intensive care unit and including pediatric and adult patients, the authors identified 2 factors associated with the occurrence of Ec-ESBL infection in previously colonized patients. These two factors were the prior use of antibiotics with β-lactam antibiotics and β-lactamase inhibitor (s), and urinary catheterization.

In intensive care hospital patients, the occurrence of ESBL-producing enterobacteriaceae infection appears to be a rare event, including in colonized patients.

The work of Ruppé et al. showed a direct link between relative fecal abundance of EScher-producing Escherichia coli and prior antibiotic intake.

This work also demonstrated a link between the value of the relative fecal abundance in Ec-ESBL and the occurrence of a urinary tract infection linked to the same clone. In particular, the authors found that women with a low relative fecal abundance rate (≤ 0.1%) had no risk of developing an Escherichia coli urinary tract infection. Conversely, the risk increased with the relative fecal abundance of Escherichia coli, but with a positive predictive value limited to 57% for relative fecal abundances between 10 and 100%.

Being tested
Control (Patients colonized rectally with ESBL-producing enterobacteria without antibiotic pressure), Case (Patients colonized rectally with ESBL-producing enterobacteriaceae, with antibiotic pressure)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Control (Patients colonized rectally with ESBL-producing enterobacteria without antibiotic pressure)Other

    For patients included in the "Control group" on discharge from hospitalization and 60 days after inclusion of patients, data will be collected either from the patient's medical file (T1Control) or during '' a telephone call from the patient (T2Control). The data collected concerns the occurrence of an infectious episode. They will also benefit from a stool sample at T1 control in order to assess the evolution kinetics of the relative fecal abundance of ESBL-producing enterobacteria in these patients who are not subjected to antibiotic pressure but subjected to other drug pressures (PPI, corticosteroids, etc.).

  • Case (Patients colonized rectally with ESBL-producing enterobacteriaceae, with antibiotic pressure)Other

    A stool culture is performed on the first stool emitted after the start of antibiotic therapy. 72 hours after the start of antibiotic therapy, a blood sample (5 ml) and a stool sample will be taken. A stool sample will be taken at the end of the antibiotic therapy and 60 days after the end of the antibiotic therapy. In the event of "normal" transit (daily bowel movements), the stool emitted 48 hours after the start of antibiotic therapy will be analyzed. If the patient does not pass stool, an eswab rectal swab will be taken. In the event of discharge from the hospital before the end of the antibiotic therapy and / or the D60 after the end of the antibiotic therapy, the patient will be given a prescription and an appointment at the collection center of the center concerned for the sample stool.

Study groups in NCT04699981
Study groupRoleWhat they receive
Control: Patients colonized rectally with ESBL-producing enterobacteria without antibiotic pressureExperimentalKnown patients colonized rectally with ESBL-producing enterobacteria and not subjected to antibiotic pressure
Receives: Other: Control (Patients colonized rectally with ESBL-producing enterobacteria without antibiotic pressure)
Case: Patients colonized rectally with ESBL-producing enterobacteriaceae, with antibiotic pressureExperimentalKnown patients colonized rectally with ESBL-producing enterobacteriaceae and subjected to antibiotic pressure (antibiotic therapy predicted greater than 24 hours) with beta-lactams or dual therapy comprising a beta-lactam. The prescription of antibiotic therapy, a decision independent of the study procedures, will be carried out as part of routine care in the context of microbiologically documented infection. The choice of molecules will be left to the discretion of clinicians.
Receives: Other: Case (Patients colonized rectally with ESBL-producing enterobacteriaceae, with antibiotic pressure)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of EBLSE

    This outcome corresponds to comparison of the relative fecal abundance (expressed as a percentage) of ESBL E and the microbiota in the 2 groups of patients.

    Measured: Day 60

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jan 2021
  2. Study start31 Mar 2022
  3. Primary completion30 Mar 2024 (estimated)
  4. Study completion31 Dec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Diagnosis
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
200 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04699981
Sponsor's protocol ID
COPROBLSE2
Acronym
COPROBLSE2
Status last verified
Sep 2023
First submitted
30 Dec 2020
Last updated
13 Sep 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Wertheim HF, Vos MC, Ott A, van Belkum A, Voss A, Kluytmans JA, van Keulen PH, Vandenbroucke-Grauls CM, Meester MH, Verbrugh HA. Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers. Lancet. 2004 Aug 21-27;364(9435):703-5. doi: 10.1016/S0140-6736(04)16897-9.

    PubMed 15325835
  • Bruyere R, Vigneron C, Bador J, Aho S, Toitot A, Quenot JP, Prin S, Charles PE. Significance of Prior Digestive Colonization With Extended-Spectrum beta-Lactamase-Producing Enterobacteriaceae in Patients With Ventilator-Associated Pneumonia. Crit Care Med. 2016 Apr;44(4):699-706. doi: 10.1097/CCM.0000000000001471.

    PubMed 26571186
  • Dubinsky-Pertzov B, Temkin E, Harbarth S, Fankhauser-Rodriguez C, Carevic B, Radovanovic I, Ris F, Kariv Y, Buchs NC, Schiffer E, Cohen Percia S, Nutman A, Fallach N, Klausner J, Carmeli Y; R-GNOSIS WP4 Study Group. Carriage of Extended-spectrum Beta-lactamase-producing Enterobacteriaceae and the Risk of Surgical Site Infection After Colorectal Surgery: A Prospective Cohort Study. Clin Infect Dis. 2019 May 2;68(10):1699-1704. doi: 10.1093/cid/ciy768.

    PubMed 30204851
  • Zahar JR, Lesprit P, Ruckly S, Eden A, Hikombo H, Bernard L, Harbarth S, Timsit JF, Brun-Buisson C; BacterCom Study Group. Predominance of healthcare-associated cases among episodes of community-onset bacteraemia due to extended-spectrum beta-lactamase-producing Enterobacteriaceae. Int J Antimicrob Agents. 2017 Jan;49(1):67-73. doi: 10.1016/j.ijantimicag.2016.09.032. Epub 2016 Nov 16.

    PubMed 27890442
  • Rodriguez-Bano J, Navarro MD, Retamar P, Picon E, Pascual A; Extended-Spectrum Beta-Lactamases-Red Espanola de Investigacion en Patologia Infecciosa/Grupo de Estudio de Infeccion Hospitalaria Group. beta-Lactam/beta-lactam inhibitor combinations for the treatment of bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli: a post hoc analysis of prospective cohorts. Clin Infect Dis. 2012 Jan 15;54(2):167-74. doi: 10.1093/cid/cir790. Epub 2011 Nov 4.

    PubMed 22057701
  • Goodman KE, Lessler J, Cosgrove SE, Harris AD, Lautenbach E, Han JH, Milstone AM, Massey CJ, Tamma PD; Antibacterial Resistance Leadership Group. A Clinical Decision Tree to Predict Whether a Bacteremic Patient Is Infected With an Extended-Spectrum beta-Lactamase-Producing Organism. Clin Infect Dis. 2016 Oct 1;63(7):896-903. doi: 10.1093/cid/ciw425. Epub 2016 Jun 28.

    PubMed 27358356
  • Augustine MR, Testerman TL, Justo JA, Bookstaver PB, Kohn J, Albrecht H, Al-Hasan MN. Clinical Risk Score for Prediction of Extended-Spectrum beta-Lactamase-Producing Enterobacteriaceae in Bloodstream Isolates. Infect Control Hosp Epidemiol. 2017 Mar;38(3):266-272. doi: 10.1017/ice.2016.292. Epub 2016 Dec 19.

    PubMed 27989244

Questions about this trial

What is this clinical trial studying?

A study testing Case (Patients colonized rectally with ESBL-producing enterobacteriaceae, with antibiotic pressure) in people with Enterobacteria Infections, run by Fondation Hôpital Saint-Joseph at 4 sites 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 5 inclusion and 5 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 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Benoit PILMIS, MD (144127820 ext. +33, bpilmis@ghpsj.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of EBLSE (time frame: Day 60). 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 NCT04699981, which also lists 7 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 13 Sep 2023.

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