<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/NCT01703299</url>
  </required_header>
  <id_info>
    <org_study_id>CRC11016</org_study_id>
    <nct_id>NCT01703299</nct_id>
  </id_info>
  <brief_title>Emergence of Resistance in Intestinal Microflora During Carbapenem Treatments</brief_title>
  <acronym>ERIC</acronym>
  <official_title>Emergence of Resistance in Intestinal Microflora During Carbapenem Treatments</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The use of carbapenems, very broad spectrum antibiotics of last resort, is becoming more&#xD;
      common due to the increased prevalence in the hospital and community of extended spectrum&#xD;
      β-lactamase (ESBL) producing gram-negative bacilli (GNB), including CTX-M type, which are&#xD;
      resistant to all other β-lactam antibiotics. Meanwhile, it creates a selective pressure&#xD;
      towards emergence of strains which are also resistant to carbapenems, placing patients in a&#xD;
      catastrophic situation of therapeutic dead-end. A better understanding of the mechanisms of&#xD;
      emergence of BGN resistant to carbapenems is necessary to optimize their use and undertake&#xD;
      preventive measures to preserve their effectiveness. The aim of the study is to evaluate and&#xD;
      describe the emergence of carbapenem-induced resistant GNB in patient intestinal microflora.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The use of carbapenems, very broad spectrum antibiotics of last resort, is becoming more&#xD;
      common due to the increased prevalence in the hospital and community of extended spectrum&#xD;
      β-lactamase (ESBL) producing gram-negative bacilli (GNB), including CTX-M type, which are&#xD;
      resistant to all other β-lactam antibiotics. Meanwhile, it creates a selective pressure&#xD;
      towards emergence of strains which are also resistant to carbapenems, placing patients in a&#xD;
      catastrophic situation of therapeutic dead-end. A better understanding of the mechanisms of&#xD;
      emergence of BGN resistant to carbapenems is necessary to optimize their use and undertake&#xD;
      preventive measures to preserve their effectiveness.&#xD;
&#xD;
      Hypotheses: Carbapenems induce in treated patients the emergence of resistant GNB in&#xD;
      intestinal flora and have an impact on colonization resistance of the gut microbiota.&#xD;
&#xD;
      Primary objective: To determine the frequency of emergence of carbapenems resistant GNB in&#xD;
      the intestinal flora at the end of a treatment by imipenem or ertapenem.&#xD;
&#xD;
      Secondary objective(s):&#xD;
&#xD;
        -  Assess the presence of carbapenem resistant GNB in the intestinal flora before&#xD;
           treatment.&#xD;
&#xD;
        -  Evaluate the presence and / or persistence of carbapenem resistant GNB in the intestinal&#xD;
           flora on day 3 of treatment, and 15 days and 1 month after the end of treatment.&#xD;
&#xD;
        -  Determine the molecular mechanisms of resistance of strains of interest.&#xD;
&#xD;
        -  Describe the gastrointestinal tract colonization by non-commensal microorganisms before&#xD;
           and after treatment (impact on colonization resistance).&#xD;
&#xD;
        -  Describe the characteristics of patients with emergence of resistance compared to&#xD;
           patients who do not.&#xD;
&#xD;
        -  Proper conservation of stool of 10 patients for metagenomic and/or metatranscriptomic&#xD;
           analysis of changes in the intestinal flora.&#xD;
&#xD;
      Primary endpoint: Presence of carbapenem resistant GNB in the stool at the end of treatment&#xD;
      in patients who did not before, after culture on selective media.&#xD;
&#xD;
      Secondary endpoints:&#xD;
&#xD;
        -  Presence of carbapenem resistant GNB in stools before treatment, at day 3 and 15 days&#xD;
           and 1 month after stopping treatment, after culture on selective media.&#xD;
&#xD;
        -  PCR and sequencing of resistance genes from strains of interest.&#xD;
&#xD;
        -  Colonization of the digestive tract by non-commensal microorganisms before and after&#xD;
           treatment.&#xD;
&#xD;
        -  Characteristics of patients with or without emergence of resistance.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">March 2014</completion_date>
  <primary_completion_date type="Actual">October 2013</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>presence of carbapenem-resistant gram-negative bacteria at the end of carbapenem treatment in faeces of patients who were free of carbapenem-resistant gram-negative bacteria before the beginning of treatment</measure>
    <time_frame>at the end of carbapenem treatment period which usually lasts between 2 and 15 days</time_frame>
    <description>faecal bacterial growth on selective culture media</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>presence of carbapenem-resistant gram-negative bacteria in patient faeces before carbapenem treatment, at day 3 of carbapenem treatment and at day 15 et day 30 after the end of carbapenem treatment</measure>
    <time_frame>before, at day 3 of carbapenem treatment and at day 15 and day 30 after the end of carbapenem treatment</time_frame>
    <description>faecal bacterial growth on selective culture media</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">35</enrollment>
  <condition>Carbapenem-induced Resistance</condition>
  <arm_group>
    <arm_group_label>imipenem-treated patients</arm_group_label>
    <description>imipenem-treated patients</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ertapenem-treated patients</arm_group_label>
    <description>ertapenem-treated patients</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      faeces, bacterial DNA&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        hospitalized patients initiating a carbapenem treatment&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age&gt; or = 18 years old&#xD;
&#xD;
          -  hospitalized&#xD;
&#xD;
          -  initiating a treatment by imipenem or ertapenem-&#xD;
&#xD;
          -  faeces harvested before the beginning of treatment&#xD;
&#xD;
          -  written informed consent from the patient or from a relative if the patient is&#xD;
             incapable of expressing his/her consent&#xD;
&#xD;
          -  reachable by phone after hospitalization (only for patients able to express their&#xD;
             consent).&#xD;
&#xD;
        Exclusion Criteria :&#xD;
&#xD;
          -  hospitalized in intensive care unit&#xD;
&#xD;
          -  concomitant antibiotic treatment (except aminosid or vancomycin for less than 4 days).&#xD;
&#xD;
        Secondary exclusion criteria :&#xD;
&#xD;
          -  introduction of other antibiotics during carbapenem treatment (except vancomycin or&#xD;
             aminosid)&#xD;
&#xD;
          -  vancomycin treatment for more than 4 days during carbapenem treatment.&#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>Antoine Andremont, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Beaujon</name>
      <address>
        <city>Clichy</city>
        <zip>92110</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Louis Mourier</name>
      <address>
        <city>Colombes</city>
        <zip>92700</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Bichat-Claude Bernard</name>
      <address>
        <city>Paris</city>
        <zip>75018</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint-Louis</name>
      <address>
        <city>Paris</city>
        <zip>75475</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Paul Brousse</name>
      <address>
        <city>Villejuif</city>
        <zip>94800</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>June 2014</verification_date>
  <study_first_submitted>September 25, 2012</study_first_submitted>
  <study_first_submitted_qc>October 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2012</study_first_posted>
  <last_update_submitted>May 12, 2015</last_update_submitted>
  <last_update_submitted_qc>May 12, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 13, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>imipenem</keyword>
  <keyword>ertapenem</keyword>
  <keyword>resistance</keyword>
  <keyword>commensal flora</keyword>
  <!-- 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/NCT01703299
org study id: CRC11016
nct id: NCT01703299
lead sponsor: 
has dmc: No
The use of carbapenems, very broad spectrum antibiotics of last resort, is becoming more
      common due to the increased prevalence in the hospital and community of extended spectrum
      β-lactamase (ESBL) producing gram-negative bacilli (GNB), including CTX-M type, which are
      resistant to all other β-lactam antibiotics. Meanwhile, it creates a selective pressure
      towards emergence of strains which are also resistant to carbapenems, placing patients in a
      catastrophic situation of therapeutic dead-end. A better understanding of the mechanisms of
      emergence of BGN resistant to carbapenems is necessary to optimize their use and undertake
      preventive measures to preserve their effectiveness. The aim of the study is to evaluate and
      describe the emergence of carbapenem-induced resistant GNB in patient intestinal microflora.
The use of carbapenems, very broad spectrum antibiotics of last resort, is becoming more
      common due to the increased prevalence in the hospital and community of extended spectrum
      β-lactamase (ESBL) producing gram-negative bacilli (GNB), including CTX-M type, which are
      resistant to all other β-lactam antibiotics. Meanwhile, it creates a selective pressure
      towards emergence of strains which are also resistant to carbapenems, placing patients in a
      catastrophic situation of therapeutic dead-end. A better understanding of the mechanisms of
      emergence of BGN resistant to carbapenems is necessary to optimize their use and undertake
      preventive measures to preserve their effectiveness.

      Hypotheses: Carbapenems induce in treated patients the emergence of resistant GNB in
      intestinal flora and have an impact on colonization resistance of the gut microbiota.

      Primary objective: To determine the frequency of emergence of carbapenems resistant GNB in
      the intestinal flora at the end of a treatment by imipenem or ertapenem.

      Secondary objective(s):

        -  Assess the presence of carbapenem resistant GNB in the intestinal flora before
           treatment.

        -  Evaluate the presence and / or persistence of carbapenem resistant GNB in the intestinal
           flora on day 3 of treatment, and 15 days and 1 month after the end of treatment.

        -  Determine the molecular mechanisms of resistance of strains of interest.

        -  Describe the gastrointestinal tract colonization by non-commensal microorganisms before
           and after treatment (impact on colonization resistance).

        -  Describe the characteristics of patients with emergence of resistance compared to
           patients who do not.

        -  Proper conservation of stool of 10 patients for metagenomic and/or metatranscriptomic
           analysis of changes in the intestinal flora.

      Primary endpoint: Presence of carbapenem resistant GNB in the stool at the end of treatment
      in patients who did not before, after culture on selective media.

      Secondary endpoints:

        -  Presence of carbapenem resistant GNB in stools before treatment, at day 3 and 15 days
           and 1 month after stopping treatment, after culture on selective media.

        -  PCR and sequencing of resistance genes from strains of interest.

        -  Colonization of the digestive tract by non-commensal microorganisms before and after
           treatment.

        -  Characteristics of patients with or without emergence of resistance.
observational model: Cohort
time perspective: Prospective
measure: presence of carbapenem-resistant gram-negative bacteria at the end of carbapenem treatment in faeces of patients who were free of carbapenem-resistant gram-negative bacteria before the beginning of treatment
time frame: at the end of carbapenem treatment period which usually lasts between 2 and 15 days
description: faecal bacterial growth on selective culture media
measure: presence of carbapenem-resistant gram-negative bacteria in patient faeces before carbapenem treatment, at day 3 of carbapenem treatment and at day 15 et day 30 after the end of carbapenem treatment
time frame: before, at day 3 of carbapenem treatment and at day 15 and day 30 after the end of carbapenem treatment
description: faecal bacterial growth on selective culture media
arm group label: imipenem-treated patients
description: imipenem-treated patients
arm group label: ertapenem-treated patients
description: ertapenem-treated patients
faeces, bacterial DNA
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Antoine Andremont, MD, PhD
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor