<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03303937</url>
  </required_header>
  <id_info>
    <org_study_id>HLM_JDR8</org_study_id>
    <nct_id>NCT03303937</nct_id>
  </id_info>
  <brief_title>Characteristics of Lower Respiratory Tract Escherichia Coli Isolates in Mechanically Ventilated Intensive Care Patients</brief_title>
  <acronym>COLOCOLI</acronym>
  <official_title>Characteristics of Lower Respiratory Tract Escherichia Coli Isolates Colonizing and Infecting Mechanically Ventilated Intensive Care Patients: a French Multicenter Prospective Collection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hôpital Louis Mourier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hôpital Louis Mourier</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prospective, multicenter observational study to collect Escherichia coli (E. coli) isolates&#xD;
      originating from mechanically ventilated intensive care unit (ICU) patients; in order to&#xD;
      characterize phenotype and genotype of E. coli strains retrieved from the lower respiratory&#xD;
      tract of ventilated patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Prospective, observational, multiple center study performed in 14 ICUs in France to collect&#xD;
      Escherichia coli (E. coli) isolates originating from mechanically ventilated intensive care&#xD;
      unit (ICU) patients; in order to characterize phenotype and genotype of E. coli strains&#xD;
      retrieved from the lower respiratory tract of ventilated patients. All E. coli isolates&#xD;
      identified in the microbiology lab and retrieved from a lung specimen (either tracheal&#xD;
      aspirate, bronchoalveolar lavage, or telescopic plugged catheter) originating from an ICU&#xD;
      patient will be kept, and stored at -80°C in brain-heart infusion broth containing glycerol&#xD;
      20 %. They will be then centralized in the investigators' research unit for further analysis&#xD;
      that includes determination of Antimicrobial susceptibility, E. coli phylotype , O-type, and&#xD;
      virulence factor gene content.&#xD;
&#xD;
      These isolates will be compared to those of two previously published collections, one from&#xD;
      the stools of community subjects, considered as commensal strains, the other from the blood&#xD;
      of bacteraemia patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 27, 2012</start_date>
  <completion_date type="Actual">June 6, 2016</completion_date>
  <primary_completion_date type="Actual">June 10, 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>phylogenetic group determination</measure>
    <time_frame>50 minutes</time_frame>
    <description>Quadruplex polymerase chain reaction (PCR) method was used to determine the E. coli phylogenetic group (A, B1, B2, C, D, E, F), or Escherichia clade I belonging</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>O-type determination</measure>
    <time_frame>50 minutes</time_frame>
    <description>polymerase chain reaction (PCR) method was used to search for the most anticipated serotypes in extra-intestinal infections : O1, O2a, O2b, O4, O6, O7, O12, O15, O16, O17, O18, O22, O25a, O25b, O45a, O75, O78</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>virulence factor (VF) gene content determination</measure>
    <time_frame>90 minutes</time_frame>
    <description>Multiplex PCR was used to detect genes encoding for eleven frequently encountered extraintestinal VFs (S and F fimbriae (sfa/foc), pili associated with pyelonephritis (papC), P adhesin (papGII, papGIII), the ferric yersiniabactin uptake receptor (fyuA), iron transport (iroN), aerobactin (aer), conjugal transfer protein (traT), N-acetylglucosamine 2-epimerase protein (neuC), hemolysin (hlyC), and the cytotoxic necrotizing factor 1(cnf1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>antimicrobial susceptibility determination</measure>
    <time_frame>24 hours</time_frame>
    <description>Antimicrobial susceptibility of each isolate was determined by disk-diffusion method according to the French Society of Microbiology. Resistance score was defined as the sum of inactive in vitro antimicrobial agents for each isolate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>presence of betalactamase</measure>
    <time_frame>90 minutes</time_frame>
    <description>Detection of gene sequences coding for the CTX-M and TEM enzymes was performed by PCR with genomic DNA</description>
  </secondary_outcome>
  <other_outcome>
    <measure>phylogenetic group belonging in other existing Escherichia coli collections</measure>
    <time_frame>24 hours</time_frame>
    <description>comparison of phylogenetic group belonging of the present isolates to those of two previously published collections, originating from the Paris area, France; one that comprises 280 E. coli strains isolated from the stools of community adult subjects in 2010 (&quot;COLIVILLE&quot;) and that can be considered as commensal strains and the other that comprises 373 E. coli strains isolated from the blood of 373 patients hospitalized in seven different hospitals, during the course of bacteraemia in 2005 (COLIBAFI study)</description>
  </other_outcome>
  <other_outcome>
    <measure>O-type distribution in other existing Escherichia coli collections</measure>
    <time_frame>24 hours</time_frame>
    <description>comparison of O-type distribution of the present isolates to those of two previously published collections, originating from the Paris area, France; one that comprises 280 E. coli strains isolated from the stools of community adult subjects in 2010 (&quot;COLIVILLE&quot;) and that can be considered as commensal strains and the other that comprises 373 E. coli strains isolated from the blood of 373 patients hospitalized in seven different hospitals, during the course of bacteraemia in 2005 (COLIBAFI study)</description>
  </other_outcome>
  <other_outcome>
    <measure>virulence factor (VF) gene content in other existing Escherichia coli collections</measure>
    <time_frame>24 hours</time_frame>
    <description>comparison of virulence factor (VF) gene content of the present isolates to those of two previously published collections, originating from the Paris area, France; one that comprises 280 E. coli strains isolated from the stools of community adult subjects in 2010 (&quot;COLIVILLE&quot;) and that can be considered as commensal strains and the other that comprises 373 E. coli strains isolated from the blood of 373 patients hospitalized in seven different hospitals, during the course of bacteraemia in 2005 (COLIBAFI study)</description>
  </other_outcome>
  <other_outcome>
    <measure>phylogenetic group belonging in E. coli isolates responsible for pneumonia and in those responsible for simple colonization</measure>
    <time_frame>median time frame is 11.5 days with a maximum of 35 days</time_frame>
    <description>comparison of phylogenetic group belonging between isolates responsible for pneumonia and those for simple colonization</description>
  </other_outcome>
  <other_outcome>
    <measure>O-type distribution in E. coli isolates responsible for pneumonia and in those responsible for simple colonization</measure>
    <time_frame>median time frame is 11.5 days with a maximum of 35 days</time_frame>
    <description>comparison of O-type distribution between isolates responsible for pneumonia and those for simple colonization</description>
  </other_outcome>
  <other_outcome>
    <measure>virulence factor (VF) gene content in E. coli isolates responsible for pneumonia and in those responsible for simple colonization</measure>
    <time_frame>median time frame is 11.5 days with a maximum of 35 days</time_frame>
    <description>comparison of virulence factor (VF) gene content between isolates responsible for pneumonia and those for simple colonization</description>
  </other_outcome>
  <enrollment type="Actual">289</enrollment>
  <condition>Nosocomial Pneumonia</condition>
  <condition>Ventilator Associated Pneumonia</condition>
  <condition>Escherichia Coli Infections</condition>
  <condition>Escherichia Coli Pneumonia</condition>
  <condition>Escherichia Coli; Diarrhea, Enteroaggregative</condition>
  <condition>Mechanical Ventilation Complication</condition>
  <eligibility>
    <study_pop>
      <textblock>
        any adult critically ill patient admitted to the ICU under invasive mechanical ventilation&#xD;
        with a positive lower respiratory tract sample for Escherichia coli&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  adult, admitted to the intensive care unit&#xD;
&#xD;
          -  under invasive mechanical ventilation&#xD;
&#xD;
          -  presence of Escherichia coli in lower respiratory tract specimen&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jean-Damien Ricard, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Béatrice La Combe, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <reference>
    <citation>Messika J, Magdoud F, Clermont O, Margetis D, Gaudry S, Roux D, Branger C, Dreyfuss D, Denamur E, Ricard JD. Pathophysiology of Escherichia coli ventilator-associated pneumonia: implication of highly virulent extraintestinal pathogenic strains. Intensive Care Med. 2012 Dec;38(12):2007-16. doi: 10.1007/s00134-012-2699-5. Epub 2012 Sep 28.</citation>
    <PMID>23052953</PMID>
  </reference>
  <reference>
    <citation>Dufour N, Clermont O, La Combe B, Messika J, Dion S, Khanna V, Denamur E, Ricard JD, Debarbieux L; ColoColi group. Bacteriophage LM33_P1, a fast-acting weapon against the pandemic ST131-O25b:H4 Escherichia coli clonal complex. J Antimicrob Chemother. 2016 Nov;71(11):3072-3080. doi: 10.1093/jac/dkw253. Epub 2016 Jul 7.</citation>
    <PMID>27387322</PMID>
  </reference>
  <reference>
    <citation>Massot M, Daubie AS, Clermont O, Jaureguy F, Couffignal C, Dahbi G, Mora A, Blanco J, Branger C, Mentre F, Eddi A, Picard B, Denamur E, The Coliville Group. Phylogenetic, virulence and antibiotic resistance characteristics of commensal strain populations of Escherichia coli from community subjects in the Paris area in 2010 and evolution over 30 years. Microbiology (Reading). 2016 Apr;162(4):642-650. doi: 10.1099/mic.0.000242. Epub 2016 Jan 28.</citation>
    <PMID>26822436</PMID>
  </reference>
  <reference>
    <citation>Lefort A, Panhard X, Clermont O, Woerther PL, Branger C, Mentre F, Fantin B, Wolff M, Denamur E; COLIBAFI Group. Host factors and portal of entry outweigh bacterial determinants to predict the severity of Escherichia coli bacteremia. J Clin Microbiol. 2011 Mar;49(3):777-83. doi: 10.1128/JCM.01902-10. Epub 2010 Dec 22.</citation>
    <PMID>21177892</PMID>
  </reference>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>September 25, 2017</study_first_submitted>
  <study_first_submitted_qc>October 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 6, 2017</study_first_posted>
  <last_update_submitted>October 5, 2017</last_update_submitted>
  <last_update_submitted_qc>October 5, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hôpital Louis Mourier</investigator_affiliation>
    <investigator_full_name>Prof Jean-Damien RICARD</investigator_full_name>
    <investigator_title>Professor of Intensive Care</investigator_title>
  </responsible_party>
  <keyword>virulence factor genes;</keyword>
  <keyword>phenotyping</keyword>
  <keyword>genotyping</keyword>
  <keyword>antimicrobial susceptibility</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Pneumonia, Ventilator-Associated</mesh_term>
    <mesh_term>Escherichia coli Infections</mesh_term>
    <mesh_term>Healthcare-Associated Pneumonia</mesh_term>
    <mesh_term>Diarrhea</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03303937
org study id: HLM_JDR8
nct id: NCT03303937
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Prospective, multicenter observational study to collect Escherichia coli (E. coli) isolates
      originating from mechanically ventilated intensive care unit (ICU) patients; in order to
      characterize phenotype and genotype of E. coli strains retrieved from the lower respiratory
      tract of ventilated patients.
Prospective, observational, multiple center study performed in 14 ICUs in France to collect
      Escherichia coli (E. coli) isolates originating from mechanically ventilated intensive care
      unit (ICU) patients; in order to characterize phenotype and genotype of E. coli strains
      retrieved from the lower respiratory tract of ventilated patients. All E. coli isolates
      identified in the microbiology lab and retrieved from a lung specimen (either tracheal
      aspirate, bronchoalveolar lavage, or telescopic plugged catheter) originating from an ICU
      patient will be kept, and stored at -80°C in brain-heart infusion broth containing glycerol
      20 %. They will be then centralized in the investigators' research unit for further analysis
      that includes determination of Antimicrobial susceptibility, E. coli phylotype , O-type, and
      virulence factor gene content.

      These isolates will be compared to those of two previously published collections, one from
      the stools of community subjects, considered as commensal strains, the other from the blood
      of bacteraemia patients.
observational model: Cohort
time perspective: Prospective
measure: phylogenetic group determination
time frame: 50 minutes
description: Quadruplex polymerase chain reaction (PCR) method was used to determine the E. coli phylogenetic group (A, B1, B2, C, D, E, F), or Escherichia clade I belonging
measure: O-type determination
time frame: 50 minutes
description: polymerase chain reaction (PCR) method was used to search for the most anticipated serotypes in extra-intestinal infections : O1, O2a, O2b, O4, O6, O7, O12, O15, O16, O17, O18, O22, O25a, O25b, O45a, O75, O78
measure: virulence factor (VF) gene content determination
time frame: 90 minutes
description: Multiplex PCR was used to detect genes encoding for eleven frequently encountered extraintestinal VFs (S and F fimbriae (sfa/foc), pili associated with pyelonephritis (papC), P adhesin (papGII, papGIII), the ferric yersiniabactin uptake receptor (fyuA), iron transport (iroN), aerobactin (aer), conjugal transfer protein (traT), N-acetylglucosamine 2-epimerase protein (neuC), hemolysin (hlyC), and the cytotoxic necrotizing factor 1(cnf1)
measure: antimicrobial susceptibility determination
time frame: 24 hours
description: Antimicrobial susceptibility of each isolate was determined by disk-diffusion method according to the French Society of Microbiology. Resistance score was defined as the sum of inactive in vitro antimicrobial agents for each isolate
measure: presence of betalactamase
time frame: 90 minutes
description: Detection of gene sequences coding for the CTX-M and TEM enzymes was performed by PCR with genomic DNA
measure: phylogenetic group belonging in other existing Escherichia coli collections
time frame: 24 hours
description: comparison of phylogenetic group belonging of the present isolates to those of two previously published collections, originating from the Paris area, France; one that comprises 280 E. coli strains isolated from the stools of community adult subjects in 2010 ("COLIVILLE") and that can be considered as commensal strains and the other that comprises 373 E. coli strains isolated from the blood of 373 patients hospitalized in seven different hospitals, during the course of bacteraemia in 2005 (COLIBAFI study)
measure: O-type distribution in other existing Escherichia coli collections
time frame: 24 hours
description: comparison of O-type distribution of the present isolates to those of two previously published collections, originating from the Paris area, France; one that comprises 280 E. coli strains isolated from the stools of community adult subjects in 2010 ("COLIVILLE") and that can be considered as commensal strains and the other that comprises 373 E. coli strains isolated from the blood of 373 patients hospitalized in seven different hospitals, during the course of bacteraemia in 2005 (COLIBAFI study)
measure: virulence factor (VF) gene content in other existing Escherichia coli collections
time frame: 24 hours
description: comparison of virulence factor (VF) gene content of the present isolates to those of two previously published collections, originating from the Paris area, France; one that comprises 280 E. coli strains isolated from the stools of community adult subjects in 2010 ("COLIVILLE") and that can be considered as commensal strains and the other that comprises 373 E. coli strains isolated from the blood of 373 patients hospitalized in seven different hospitals, during the course of bacteraemia in 2005 (COLIBAFI study)
measure: phylogenetic group belonging in E. coli isolates responsible for pneumonia and in those responsible for simple colonization
time frame: median time frame is 11.5 days with a maximum of 35 days
description: comparison of phylogenetic group belonging between isolates responsible for pneumonia and those for simple colonization
measure: O-type distribution in E. coli isolates responsible for pneumonia and in those responsible for simple colonization
time frame: median time frame is 11.5 days with a maximum of 35 days
description: comparison of O-type distribution between isolates responsible for pneumonia and those for simple colonization
measure: virulence factor (VF) gene content in E. coli isolates responsible for pneumonia and in those responsible for simple colonization
time frame: median time frame is 11.5 days with a maximum of 35 days
description: comparison of virulence factor (VF) gene content between isolates responsible for pneumonia and those for simple colonization
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jean-Damien Ricard, MD, PhD
role: Study Director
affiliation: Assistance Publique - Hôpitaux de Paris
last name: Béatrice La Combe, MD
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
citation: Messika J, Magdoud F, Clermont O, Margetis D, Gaudry S, Roux D, Branger C, Dreyfuss D, Denamur E, Ricard JD. Pathophysiology of Escherichia coli ventilator-associated pneumonia: implication of highly virulent extraintestinal pathogenic strains. Intensive Care Med. 2012 Dec;38(12):2007-16. doi: 10.1007/s00134-012-2699-5. Epub 2012 Sep 28.
PMID: 23052953
citation: Dufour N, Clermont O, La Combe B, Messika J, Dion S, Khanna V, Denamur E, Ricard JD, Debarbieux L; ColoColi group. Bacteriophage LM33_P1, a fast-acting weapon against the pandemic ST131-O25b:H4 Escherichia coli clonal complex. J Antimicrob Chemother. 2016 Nov;71(11):3072-3080. doi: 10.1093/jac/dkw253. Epub 2016 Jul 7.
PMID: 27387322
citation: Massot M, Daubie AS, Clermont O, Jaureguy F, Couffignal C, Dahbi G, Mora A, Blanco J, Branger C, Mentre F, Eddi A, Picard B, Denamur E, The Coliville Group. Phylogenetic, virulence and antibiotic resistance characteristics of commensal strain populations of Escherichia coli from community subjects in the Paris area in 2010 and evolution over 30 years. Microbiology (Reading). 2016 Apr;162(4):642-650. doi: 10.1099/mic.0.000242. Epub 2016 Jan 28.
PMID: 26822436
citation: Lefort A, Panhard X, Clermont O, Woerther PL, Branger C, Mentre F, Fantin B, Wolff M, Denamur E; COLIBAFI Group. Host factors and portal of entry outweigh bacterial determinants to predict the severity of Escherichia coli bacteremia. J Clin Microbiol. 2011 Mar;49(3):777-83. doi: 10.1128/JCM.01902-10. Epub 2010 Dec 22.
PMID: 21177892
responsible party type: Principal Investigator
investigator affiliation: Hôpital Louis Mourier
investigator full name: Prof Jean-Damien RICARD
investigator title: Professor of Intensive Care
mesh term: Pneumonia
mesh term: Pneumonia, Ventilator-Associated
mesh term: Escherichia coli Infections
mesh term: Healthcare-Associated Pneumonia
mesh term: Diarrhea
sharing ipd: Undecided