<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/NCT02265445</url>
  </required_header>
  <id_info>
    <org_study_id>P130949</org_study_id>
    <secondary_id>AOM 13063</secondary_id>
    <nct_id>NCT02265445</nct_id>
  </id_info>
  <brief_title>Deescalating Carbapenems in Hospital Setting</brief_title>
  <acronym>CARBEPARGNE</acronym>
  <official_title>Deescalating Carbapenems in Hospital Setting: a Multicentre Randomized Controlled Study Comparing Carbapenem Continuation and Switch to Another Beta-lactam for the Treatment of Infections Due to ESBL-producing Enterobacteriaceae</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 study aims to evaluate a deescalating therapeutic strategy (switch the carbapenem to&#xD;
      another beta-lactam for which the isolated pathogen is susceptible) in patients with&#xD;
      well-defined ESBL-PE infections (usual sites of infections and non severe infections).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Carbapenems are considered the antibiotics of choice for the treatment of infections due to&#xD;
      expanded-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-PE). Their use is readily&#xD;
      increasing because of the pandemic of ESBL-PE. However, the future of these drugs is&#xD;
      challenged by the worldwide emergency of new resistance mechanisms in the same pathogens,&#xD;
      particularly the carbapenemases. This resistance makes these drugs inactive and gives no&#xD;
      therapeutic options for patients. Resistance to carbapenems is strongly associated with the&#xD;
      use of these drugs, because of their large spectrum and strong impact on the host flora.&#xD;
      Consequently, the correct use of these drugs is an important public health objective. In&#xD;
      France, the CA-SFM (Committee on Antimicrobial of the French Society for Microbiology) has&#xD;
      suggested alternative strategies with narrow spectrum beta-lactam for the treatment of&#xD;
      ESBL-PE infections, including 3rd or 4th cephalosporins, cefoxitin and penicillins with&#xD;
      beta-lactamase inhibitors. A recent analysis including 6 prospective cohort studies of&#xD;
      bloodstream infections due to ESBL-producing Escherichia coli did not find an excess of&#xD;
      mortality or a longer length of hospital stay for patients receiving penicillin with&#xD;
      beta-lactamase inhibitors, as compared to patients treated with carbapenems, after adjusting&#xD;
      by confounding factors. As patients receiving carbapenems seem to be more severely affected,&#xD;
      the efficacy and safety of the alternative strategy remain unproved. A randomized study is&#xD;
      therefore needed to evaluate a deescalating therapeutic strategy (switch the carbapenem to&#xD;
      another beta-lactam for which the isolated pathogen is susceptible) in patients with&#xD;
      well-defined ESBL-PE infections (usual sites of infections and non severe infections). The&#xD;
      objectives of the present study are to demonstrate that the alternative strategy of&#xD;
      deescalating therapy is not inferior to a strategy maintaining the carbapenem in terms of&#xD;
      clinical cure, survival, lack of relapse and microbiological cure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The study was stopped for recruitment defect&#xD;
  </why_stopped>
  <start_date>June 2015</start_date>
  <completion_date type="Actual">June 2016</completion_date>
  <primary_completion_date type="Actual">June 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical response</measure>
    <time_frame>7 days after the end of therapy</time_frame>
    <description>The main outcome will be the favorable response defined by criteria adapted to site of infection including clinical cure with resolution of sepsis, survival, microbiological eradication either documented or suspected, and the absence of a new antibiotic course for the treatment of the same ESBL-PE) at day 7 after the end of therapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Vital status of patients</measure>
    <time_frame>60 days after the initiation of therapy</time_frame>
    <description>Vital status at day 60 after initiation therapy ; Relapse at day 60 following initiation of therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>absence of relapse of the infection due to the same ESBL-PE strain</measure>
    <time_frame>60 days after the initiation of therapy</time_frame>
    <description>Vital status at day 60 after initiation therapy ; Relapse at day 60 following initiation of therapy</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Urinary Infection</condition>
  <condition>Digestive Infection</condition>
  <condition>Biliary Infection</condition>
  <condition>Expanded-spectrum Beta-lactamase Producing ESBL</condition>
  <arm_group>
    <arm_group_label>Maintaining carbapenem therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intravenous therapy, Maintaining carbapenem therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Deescalation therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Switch for a narrow spectrum beta-lactam active on the causative ESBL-PE. Deescalation therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Deescalation therapy</intervention_name>
    <description>Intravenous therapy Switch for a narrow spectrum beta-lactam active on the causative ESBL-PE.</description>
    <arm_group_label>Deescalation therapy</arm_group_label>
    <other_name>Switch for a narrow spectrum beta-lactam active</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Maintaining carbapenem therapy</intervention_name>
    <description>Intravenous therapy, Maintaining carbapenem therapy</description>
    <arm_group_label>Maintaining carbapenem therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Hospitalization in conventional ward; (3) Receiving a curative treatment with a&#xD;
             carbapenem for at least 24 hours and less than 3 days for a recent infection due to an&#xD;
             ESBL-PE, either initially or secondary documented&#xD;
&#xD;
          -  With a site of infection originating from the urinary, digestive or biliary tract&#xD;
&#xD;
          -  Identification of an ESBL-PE for which susceptibility results (by the method of discs)&#xD;
             have shown to be susceptible to more narrow spectrum beta-lactams (cephalosporins,&#xD;
             b-lactamase inhibitors, monobactams)&#xD;
&#xD;
          -  With sepsis signs and symptoms controlled after initiation of antibiotic therapy&#xD;
&#xD;
          -  For a community-acquired or hospital-acquired infection.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Neutropenia (PNN &lt; 500/mm3)&#xD;
&#xD;
          -  Hospitalization in intensive care unit or bone marrow transplant unit&#xD;
&#xD;
          -  Documented polymicrobial infection&#xD;
&#xD;
          -  Culture of an ESBL-PE susceptible to an orally active drug (such as fluoroquinolones,&#xD;
             cotrimoxazole) and possible use of one of these drugs&#xD;
&#xD;
          -  Need to treat a EBLSE infection(s) wtih more than drug other than carbapenems&#xD;
&#xD;
          -  Need to maintain an association with an aminoglycoside&#xD;
&#xD;
          -  Colonization without signs and symptoms of sepsis&#xD;
&#xD;
          -  Sepsis signs and symptoms not controlled at the time of enrolment&#xD;
&#xD;
          -  Known allergy to beta-lactams&#xD;
&#xD;
          -  Failure to complete medical examination&#xD;
&#xD;
          -  Absence of signed written consent.&#xD;
&#xD;
          -  Patient without healthcare insurance (French social security, CMU or AME)&#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>Phillipe LESPRIT, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <verification_date>February 2017</verification_date>
  <study_first_submitted>October 2, 2014</study_first_submitted>
  <study_first_submitted_qc>October 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 16, 2014</study_first_posted>
  <last_update_submitted>February 20, 2017</last_update_submitted>
  <last_update_submitted_qc>February 20, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">February 23, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Carbapenems therapy/ESBL infections/Deescalation</keyword>
  <keyword>due to ESBL-PE</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Urinary Tract Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>beta-Lactams</mesh_term>
  </intervention_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/NCT02265445
org study id: P130949
secondary id: AOM 13063
nct id: NCT02265445
lead sponsor: 
has dmc: No
The study aims to evaluate a deescalating therapeutic strategy (switch the carbapenem to
      another beta-lactam for which the isolated pathogen is susceptible) in patients with
      well-defined ESBL-PE infections (usual sites of infections and non severe infections).
Carbapenems are considered the antibiotics of choice for the treatment of infections due to
      expanded-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-PE). Their use is readily
      increasing because of the pandemic of ESBL-PE. However, the future of these drugs is
      challenged by the worldwide emergency of new resistance mechanisms in the same pathogens,
      particularly the carbapenemases. This resistance makes these drugs inactive and gives no
      therapeutic options for patients. Resistance to carbapenems is strongly associated with the
      use of these drugs, because of their large spectrum and strong impact on the host flora.
      Consequently, the correct use of these drugs is an important public health objective. In
      France, the CA-SFM (Committee on Antimicrobial of the French Society for Microbiology) has
      suggested alternative strategies with narrow spectrum beta-lactam for the treatment of
      ESBL-PE infections, including 3rd or 4th cephalosporins, cefoxitin and penicillins with
      beta-lactamase inhibitors. A recent analysis including 6 prospective cohort studies of
      bloodstream infections due to ESBL-producing Escherichia coli did not find an excess of
      mortality or a longer length of hospital stay for patients receiving penicillin with
      beta-lactamase inhibitors, as compared to patients treated with carbapenems, after adjusting
      by confounding factors. As patients receiving carbapenems seem to be more severely affected,
      the efficacy and safety of the alternative strategy remain unproved. A randomized study is
      therefore needed to evaluate a deescalating therapeutic strategy (switch the carbapenem to
      another beta-lactam for which the isolated pathogen is susceptible) in patients with
      well-defined ESBL-PE infections (usual sites of infections and non severe infections). The
      objectives of the present study are to demonstrate that the alternative strategy of
      deescalating therapy is not inferior to a strategy maintaining the carbapenem in terms of
      clinical cure, survival, lack of relapse and microbiological cure.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Clinical response
time frame: 7 days after the end of therapy
description: The main outcome will be the favorable response defined by criteria adapted to site of infection including clinical cure with resolution of sepsis, survival, microbiological eradication either documented or suspected, and the absence of a new antibiotic course for the treatment of the same ESBL-PE) at day 7 after the end of therapy.
measure: Vital status of patients
time frame: 60 days after the initiation of therapy
description: Vital status at day 60 after initiation therapy ; Relapse at day 60 following initiation of therapy
measure: absence of relapse of the infection due to the same ESBL-PE strain
time frame: 60 days after the initiation of therapy
description: Vital status at day 60 after initiation therapy ; Relapse at day 60 following initiation of therapy
arm group label: Maintaining carbapenem therapy
arm group type: Active Comparator
description: Intravenous therapy, Maintaining carbapenem therapy
arm group label: Deescalation therapy
arm group type: Active Comparator
description: Switch for a narrow spectrum beta-lactam active on the causative ESBL-PE. Deescalation therapy
intervention type: Drug
intervention name: Deescalation therapy
description: Intravenous therapy Switch for a narrow spectrum beta-lactam active on the causative ESBL-PE.
arm group label: Deescalation therapy
other name: Switch for a narrow spectrum beta-lactam active
intervention type: Drug
intervention name: Maintaining carbapenem therapy
description: Intravenous therapy, Maintaining carbapenem therapy
arm group label: Maintaining carbapenem therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Phillipe LESPRIT, MD
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Urinary Tract Infections
mesh term: beta-Lactams
sharing ipd: Undecided