<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/NCT03012360</url>
  </required_header>
  <id_info>
    <org_study_id>2015_66</org_study_id>
    <secondary_id>2016-000735-41</secondary_id>
    <nct_id>NCT03012360</nct_id>
  </id_info>
  <brief_title>Antimicrobial Treatment in Patients With Ventilator-associated Tracheobronchitis</brief_title>
  <acronym>TAVeM2</acronym>
  <official_title>Antimicrobial Treatment in Patients With Ventilator-associated Tracheobronchitis: a Prospective Randomized Placebo-controlled Double-blind Multicenter Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Lille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministry of Health, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Lille</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>
      Antimicrobial treatment could be beneficial in patients with ventilator-associated&#xD;
      tracheobronchitis (VAT). The hypothesis of this study is that antibiotic treatment for VAT (3&#xD;
      or 7 days), compared with no antibiotic treatment, would reduce the incidence of transition&#xD;
      from VAT to ventilator-associated pneumonia (VAP).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The main objective of this randomized controlled multicenter double-blind trial is to assess&#xD;
      the efficiency of two durations (3 or 7 days) of antibiotic treatment for VAT, compared with&#xD;
      no antibiotic treatment, in reducing the incidence of transition from VAT to&#xD;
      ventilator-associated pneumonia (VAP).&#xD;
&#xD;
      Secondary objectives are to determine the impact of two durations (3 or 7 days) of antibiotic&#xD;
      treatment for VAT, compared with no antibiotic treatment, on:&#xD;
&#xD;
        -  duration of mechanical-ventilation free days&#xD;
&#xD;
        -  duration of antibiotic free days&#xD;
&#xD;
        -  length of ICU stay&#xD;
&#xD;
        -  mortality at day 28 and day 90&#xD;
&#xD;
        -  incidence of ICU-acquired colonization related to multidrug resistant (MDR) bacteria&#xD;
&#xD;
        -  incidence of ICU-acquired infection related to MDR bacteria&#xD;
&#xD;
        -  incidence of ventilator-associated events After informed consent, patients will be&#xD;
           randomized (1:1:1) to receive 0 (control group), 3 or 7 days (experimental groups) of&#xD;
           antibiotic treatment for VAT&#xD;
&#xD;
      Antibiotic treatment is standardized, based on the time of onset of VAT, and presence of risk&#xD;
      factors for MDR bacteria:&#xD;
&#xD;
        -  patients with early-onset VAT with no risk factor for MDR bacteria will receive&#xD;
           ceftriaxone (2 g iv every 24h).&#xD;
&#xD;
        -  patients with late-onset VAT (after day 4 of mechanical ventilation), or with at least&#xD;
           one risk factor for MDR bacteria will receive imipenem (1 g iv every 8h), and&#xD;
           ciprofloxacin (400 mg iv every 8h) as empirical treatment. When methicillin-resistant&#xD;
           Staphylococcus aureus is suspected, linezolid (600 mg iv every 12h) will be added to&#xD;
           empirical treatment.&#xD;
&#xD;
      Patients randomized in control group will receive 7 days of placebo, and those randomized in&#xD;
      the first experimental arm (3 days of antibiotics) will receive 4 days of placebo.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 8, 2018</start_date>
  <completion_date type="Anticipated">September 2023</completion_date>
  <primary_completion_date type="Anticipated">September 2023</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The percentage of patients with a transition from VAT to VAP,</measure>
    <time_frame>from randomization to day 28 (4 weeks)</time_frame>
    <description>VAP is defined using the following criteria:&#xD;
new or progressive pulmonary infiltrate&#xD;
two of the following criteria: temperature &gt;38°C or &lt;36.5°C leukocyte count &gt;12,000/μL or &lt;4,000/μL purulent endotracheal aspirate&#xD;
positive tracheal aspirate (≥105 cfu/mL) or bronchoalveolar lavage (≥104 cfu/mL).&#xD;
VAP will be considered as subsequent to VAT, when it is diagnosed &gt;24h after VAT occurrence. Only first episodes of VAP diagnosed &gt;48h after starting mechanical ventilation will be taken into account.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>duration of mechanical ventilation-free days</measure>
    <time_frame>from randomization to day 28 (4 weeks)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>duration of antibiotic free-days</measure>
    <time_frame>from randomization to day 28 (4 weeks)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>length of ICU stay</measure>
    <time_frame>from randomization to day 28 (4 weeks)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>mortality</measure>
    <time_frame>at day 28 and day 90 after randomization</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>percentage of patients with ICU-acquired colonization related to MDR bacteria</measure>
    <time_frame>from randomization to day 28 (4 weeks)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>percentage of patients with ventilator-associated events</measure>
    <time_frame>from randomization to day 28 (4 weeks)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>percentage of patients with ICU-acquired infection related to MDR bacteria</measure>
    <time_frame>from randomization to day 28 (4 weeks)</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">154</enrollment>
  <condition>Mechanical Ventilation Complication</condition>
  <condition>Critical Illness</condition>
  <arm_group>
    <arm_group_label>no antibiotic treatment for VAT</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>3 days of placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>antibiotic treatment for 3 days</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients randomized in one of the two experimental groups will receive 3 days of antimicrobials. Antibiotic treatment is standardized, based on the time of onset of VAT, and presence of risk factors for MDR bacteria:&#xD;
patients with early-onset VAT (&lt; 5 days of mechanical ventilation), with no risk factor for MDR will receive ceftriaxone .&#xD;
patients with late-onset VAT (≥5 days of mechanical ventilation), or with at least one risk factor for multidrug resistant bacteria will receive imipenem , and ciprofloxacin as empirical treatment.&#xD;
When methicillin-resistant Staphylococcus aureus (MRSA) is suspected linezolid will be added to empirical treatment.&#xD;
3 days of imipenem and ciprofloxacin with optional linezolid, followed by 4 d of placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ceftriaxone</intervention_name>
    <description>2 g iv every 24h</description>
    <arm_group_label>antibiotic treatment for 3 days</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ciprofloxacin</intervention_name>
    <description>400 mg iv every 8h</description>
    <arm_group_label>antibiotic treatment for 3 days</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>imipenem</intervention_name>
    <description>1 g iv every 8h</description>
    <arm_group_label>antibiotic treatment for 3 days</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>linezolid</intervention_name>
    <description>600 mg iv every 12h</description>
    <arm_group_label>antibiotic treatment for 3 days</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>The SSI 0.9% or dextrose 5% used are based on routine procedure in different participating centers.Placebo will be prepared using IV bags, with the same of quantity as IMP</description>
    <arm_group_label>antibiotic treatment for 3 days</arm_group_label>
    <arm_group_label>no antibiotic treatment for VAT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All adult patients hospitalized in the ICU with a first episode of VAT diagnosed &gt;48&#xD;
             hours after starting invasive mechanical ventilation are eligible for this study.&#xD;
&#xD;
        VAT is defined using the following criteria:&#xD;
&#xD;
          1. absence of new infiltrate on chest X ray&#xD;
&#xD;
          2. two of the three following conditions: fever &gt; 38.5 °C or &lt;36.5, leucocyte count &gt;&#xD;
             than 12 000 cells per μL or &lt;than 4000 cells per μL purulent tracheal secretions&#xD;
&#xD;
          3. and positive tracheal aspirate (≥105 cfu/mL)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  long-term tracheostomy at ICU admission&#xD;
&#xD;
          -  patients who develop VAP before VAT&#xD;
&#xD;
          -  patients already receiving antibiotics active against all the microorganisms&#xD;
             responsible for VAT&#xD;
&#xD;
          -  severe immunosuppression&#xD;
&#xD;
          -  pregnancy or breastfeeding&#xD;
&#xD;
          -  patients &lt;18 years&#xD;
&#xD;
          -  patients already included in another study, with potential interaction with the&#xD;
             primary objective of the current study&#xD;
&#xD;
          -  known resistance to imipenem and ciprofloxacin of bacteria responsible for VAT&#xD;
&#xD;
          -  treatment limitation decisions&#xD;
&#xD;
          -  moribund patients (likely to die within 24 h)&#xD;
&#xD;
          -  allergy to any of study drugs: hypersensitivity to any carbapenem, severe&#xD;
             hypersensitivity (for example anaphylactic reaction or severe cutaneous reaction) to&#xD;
             any other antibiotic form beta-lactam group (such as penicillin or cephalosporin),&#xD;
             severe hypersensitivity (for example anaphylactic reaction) to any other antibiotic&#xD;
             from beta-lactam group (penicillin, monobactam or carbapenem), hypersensitivity to&#xD;
             quinolones&#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>Saad NSEIR, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Lille</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Saad NSEIR, MD,PhD</last_name>
    <phone>3 20 44 40 84</phone>
    <phone_ext>+33</phone_ext>
    <email>saadalla.nseir@chru-lille.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hôpital Roger Salengro, CHRU</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Saad NSEIR, MD,PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>December 13, 2016</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <last_update_submitted>August 16, 2022</last_update_submitted>
  <last_update_submitted_qc>August 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 17, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Infectiology</keyword>
  <keyword>Biology of infectious agents</keyword>
  <keyword>Hygiene</keyword>
  <keyword>Pneumology</keyword>
  <keyword>Critical Care</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ciprofloxacin</mesh_term>
    <mesh_term>Ceftriaxone</mesh_term>
    <mesh_term>Linezolid</mesh_term>
    <mesh_term>Imipenem</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03012360
org study id: 2015_66
secondary id: 2016-000735-41
nct id: NCT03012360
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Antimicrobial treatment could be beneficial in patients with ventilator-associated
      tracheobronchitis (VAT). The hypothesis of this study is that antibiotic treatment for VAT (3
      or 7 days), compared with no antibiotic treatment, would reduce the incidence of transition
      from VAT to ventilator-associated pneumonia (VAP).
The main objective of this randomized controlled multicenter double-blind trial is to assess
      the efficiency of two durations (3 or 7 days) of antibiotic treatment for VAT, compared with
      no antibiotic treatment, in reducing the incidence of transition from VAT to
      ventilator-associated pneumonia (VAP).

      Secondary objectives are to determine the impact of two durations (3 or 7 days) of antibiotic
      treatment for VAT, compared with no antibiotic treatment, on:

        -  duration of mechanical-ventilation free days

        -  duration of antibiotic free days

        -  length of ICU stay

        -  mortality at day 28 and day 90

        -  incidence of ICU-acquired colonization related to multidrug resistant (MDR) bacteria

        -  incidence of ICU-acquired infection related to MDR bacteria

        -  incidence of ventilator-associated events After informed consent, patients will be
           randomized (1:1:1) to receive 0 (control group), 3 or 7 days (experimental groups) of
           antibiotic treatment for VAT

      Antibiotic treatment is standardized, based on the time of onset of VAT, and presence of risk
      factors for MDR bacteria:

        -  patients with early-onset VAT with no risk factor for MDR bacteria will receive
           ceftriaxone (2 g iv every 24h).

        -  patients with late-onset VAT (after day 4 of mechanical ventilation), or with at least
           one risk factor for MDR bacteria will receive imipenem (1 g iv every 8h), and
           ciprofloxacin (400 mg iv every 8h) as empirical treatment. When methicillin-resistant
           Staphylococcus aureus is suspected, linezolid (600 mg iv every 12h) will be added to
           empirical treatment.

      Patients randomized in control group will receive 7 days of placebo, and those randomized in
      the first experimental arm (3 days of antibiotics) will receive 4 days of placebo.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: The percentage of patients with a transition from VAT to VAP,
time frame: from randomization to day 28 (4 weeks)
description: VAP is defined using the following criteria:
new or progressive pulmonary infiltrate
two of the following criteria: temperature >38°C or <36.5°C leukocyte count >12,000/μL or <4,000/μL purulent endotracheal aspirate
positive tracheal aspirate (≥105 cfu/mL) or bronchoalveolar lavage (≥104 cfu/mL).
VAP will be considered as subsequent to VAT, when it is diagnosed >24h after VAT occurrence. Only first episodes of VAP diagnosed >48h after starting mechanical ventilation will be taken into account.
measure: duration of mechanical ventilation-free days
time frame: from randomization to day 28 (4 weeks)
measure: duration of antibiotic free-days
time frame: from randomization to day 28 (4 weeks)
measure: length of ICU stay
time frame: from randomization to day 28 (4 weeks)
measure: mortality
time frame: at day 28 and day 90 after randomization
measure: percentage of patients with ICU-acquired colonization related to MDR bacteria
time frame: from randomization to day 28 (4 weeks)
measure: percentage of patients with ventilator-associated events
time frame: from randomization to day 28 (4 weeks)
measure: percentage of patients with ICU-acquired infection related to MDR bacteria
time frame: from randomization to day 28 (4 weeks)
arm group label: no antibiotic treatment for VAT
arm group type: Placebo Comparator
description: 3 days of placebo
arm group label: antibiotic treatment for 3 days
arm group type: Experimental
description: Patients randomized in one of the two experimental groups will receive 3 days of antimicrobials. Antibiotic treatment is standardized, based on the time of onset of VAT, and presence of risk factors for MDR bacteria:
patients with early-onset VAT (< 5 days of mechanical ventilation), with no risk factor for MDR will receive ceftriaxone .
patients with late-onset VAT (≥5 days of mechanical ventilation), or with at least one risk factor for multidrug resistant bacteria will receive imipenem , and ciprofloxacin as empirical treatment.
When methicillin-resistant Staphylococcus aureus (MRSA) is suspected linezolid will be added to empirical treatment.
3 days of imipenem and ciprofloxacin with optional linezolid, followed by 4 d of placebo
intervention type: Drug
intervention name: ceftriaxone
description: 2 g iv every 24h
arm group label: antibiotic treatment for 3 days
intervention type: Drug
intervention name: ciprofloxacin
description: 400 mg iv every 8h
arm group label: antibiotic treatment for 3 days
intervention type: Drug
intervention name: imipenem
description: 1 g iv every 8h
arm group label: antibiotic treatment for 3 days
intervention type: Drug
intervention name: linezolid
description: 600 mg iv every 12h
arm group label: antibiotic treatment for 3 days
intervention type: Drug
intervention name: placebo
description: The SSI 0.9% or dextrose 5% used are based on routine procedure in different participating centers.Placebo will be prepared using IV bags, with the same of quantity as IMP
arm group label: antibiotic treatment for 3 days
arm group label: no antibiotic treatment for VAT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Saad NSEIR, MD, PhD
role: Principal Investigator
affiliation: University Hospital, Lille
last name: Saad NSEIR, MD,PhD
phone: 3 20 44 40 84
phone ext: +33
email: saadalla.nseir@chru-lille.fr
facility: 
status: Recruiting
investigator: 
country: France
responsible party type: Sponsor
mesh term: Critical Illness
mesh term: Ciprofloxacin
mesh term: Ceftriaxone
mesh term: Linezolid
mesh term: Imipenem
sharing ipd: No