<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/NCT02265406</url>
  </required_header>
  <id_info>
    <org_study_id>PROPHY-VAP</org_study_id>
    <nct_id>NCT02265406</nct_id>
  </id_info>
  <brief_title>PROPHY-VAP: Prevention of Early Ventilation Acquired Pneumonia (VAP) in Brain Injured Patients by a Single Dose of Ceftriaxone</brief_title>
  <acronym>PROPHY-VAP</acronym>
  <official_title>PROPHY-VAP: Prevention of Early Ventilation Acquired Pneumonia (VAP) in Brain Injured Patients by a Single Dose of Ceftriaxone</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Poitiers University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Poitiers University Hospital</source>
  <brief_summary>
    <textblock>
      Ventilation-associated pneumonia (VAP) is the main site of healthcare-associated infections&#xD;
      in the brain injured patients, with an incidence rate of 22% to 58%. VAP increases&#xD;
      morbi-mortality, length of stay in intensive care and overall management costs. The&#xD;
      prevention of ICU nosocomial infections depends on several measures : orotracheal intubation&#xD;
      route, maintaining tube cuff pressure between 25 and 30 cm of water (H2O), maintaining a&#xD;
      semi-seated position &gt;= 30°, nasal and oropharyngeal care at regular intervals, striving to&#xD;
      avoid unscheduled extubation, and use of a written sedation-analgesia algorithm allowing for&#xD;
      early weaning from ventilation. Two randomized study show that administration of antibiotic&#xD;
      therapy after intubation reduces the risk of early VAP incidence. However, in clinical&#xD;
      practice, its administration solely purposes of limiting VAP occurence is not presently&#xD;
      recommended. Indeed, to date no placebo blind controlled study was been realized and the fear&#xD;
      of development of bacterial resistance remains stronger than the efficiency of this&#xD;
      prevention measure. This aim of the present study is to show by a placebo randomized study&#xD;
      that 2g of Ceftriaxone within 8 hours post-intubation after a brain injury decrease the risk&#xD;
      of occurence an early VAP.&#xD;
&#xD;
      Ancillary study An ancillary study is performed in 2 centres which routinely practice rectal&#xD;
      swabs at admission and discharge of ICU, to survey intestinal flora (CHU of Angers and CHU of&#xD;
      Rennes). The goal of this study is to compare the incidence of acquired cephalosporin&#xD;
      resistant gram negative bacteria at the discharge of ICU between the 2 groups of patients,&#xD;
      receiving or not ceftriaxone.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2015</start_date>
  <completion_date type="Actual">July 25, 2020</completion_date>
  <primary_completion_date type="Actual">July 25, 2020</primary_completion_date>
  <phase>Phase 3</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>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of early VAP, proportion of patients who develop a VAP within the 7 first day after mechanical ventilation (the 7th day included), confirm with microbiological culture, within all included patients.</measure>
    <time_frame>30 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>- Incidence of late VAP (&gt; 7 jours)</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- Global incidence of VAP during intensive care period (limited to day 60)</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- Type of bacteria and their sensitivity for early or late VAP,</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- Time between inclusion and occurence of the first VAP (limited to day 28),</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- Length of the first period of mechanical ventilation during the intensive care period,</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- Time between inclusion and the first spontaneous ventilation test (limited to day 28),</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- Length of antibiotherapy during intensive care period,</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- Length of intensive care, limited to 60 days,</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- Length of stay in intensive care unit, limited to 60 days,</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- Length of stay at the hospital, limited to 60 days,</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- Neurological prognosis at the discharge of the intensive care unit,</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- Mortality at day 28 and 60.</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- Incidence of ventilated associated event (limited to day 60)</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- Comparison of the global incidence of VAP according to the diagnosis defined by &quot;American Thoracic Society&quot; or by &quot;Centers for Disease Control&quot;</measure>
    <time_frame>30 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">354</enrollment>
  <condition>Early Ventilation Acquired Pneumonia in Brain Injured Patients</condition>
  <arm_group>
    <arm_group_label>Ceftriaxone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Sodium Chloride</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anti-Infective Agents</intervention_name>
    <arm_group_label>Ceftriaxone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Sodium Chloride</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Brain injured patients with a Glasgow scale score ≤ 12 who require ventilation more&#xD;
             than 48 hours&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient with a high risk of death within the 48 first hours after admission,&#xD;
&#xD;
          -  Patient intubated for more than12 hours&#xD;
&#xD;
          -  Intubation after the 48th hours after admission&#xD;
&#xD;
          -  Coverage to cardiopulmonary arrest&#xD;
&#xD;
          -  Coma due to a tumor, an infectious disease or a cardiac arrest&#xD;
&#xD;
          -  Previous hospitalisation within the last month before admission for coma&#xD;
&#xD;
          -  béta-lactamines allergy&#xD;
&#xD;
          -  Patient who receive already antibiotics at the admission for a previous infection&#xD;
&#xD;
          -  Prophylactic antibiotic due to be done within 24 hours following the randomisation&#xD;
&#xD;
          -  Patient Intubated through a tracheal tube with subglottic secretion aspiration&#xD;
&#xD;
          -  Patient with a tracheotomy&#xD;
&#xD;
          -  Patient or family refuse to be involved in the study&#xD;
&#xD;
          -  Use of Ceftriaxone within 2 days before enrolment&#xD;
&#xD;
          -  Participation in another research protocol focusing on an anti-infective treatment or&#xD;
             on a measure decreasing the risk of infection&#xD;
&#xD;
          -  Patients not affiliated to a social security scheme, Pregnant woman or breast-feeding&#xD;
             mother, Patients deprived of their liberty by judicial or administrative decision&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University Hospital of Angers</name>
      <address>
        <city>Angers</city>
        <zip>49933</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU</name>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital of Nantes</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital of Poitiers</name>
      <address>
        <city>Poitiers</city>
        <zip>86021</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital of Rennes</name>
      <address>
        <city>Rennes</city>
        <zip>35033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas GEERAERTS</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Djilali ELAROUSSI</name>
      <address>
        <city>Tours</city>
        <zip>37000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>October 9, 2014</study_first_submitted>
  <study_first_submitted_qc>October 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <last_update_submitted>February 2, 2021</last_update_submitted>
  <last_update_submitted_qc>February 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Infective Agents</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02265406
org study id: PROPHY-VAP
nct id: NCT02265406
lead sponsor: 
Ventilation-associated pneumonia (VAP) is the main site of healthcare-associated infections
      in the brain injured patients, with an incidence rate of 22% to 58%. VAP increases
      morbi-mortality, length of stay in intensive care and overall management costs. The
      prevention of ICU nosocomial infections depends on several measures : orotracheal intubation
      route, maintaining tube cuff pressure between 25 and 30 cm of water (H2O), maintaining a
      semi-seated position >= 30°, nasal and oropharyngeal care at regular intervals, striving to
      avoid unscheduled extubation, and use of a written sedation-analgesia algorithm allowing for
      early weaning from ventilation. Two randomized study show that administration of antibiotic
      therapy after intubation reduces the risk of early VAP incidence. However, in clinical
      practice, its administration solely purposes of limiting VAP occurence is not presently
      recommended. Indeed, to date no placebo blind controlled study was been realized and the fear
      of development of bacterial resistance remains stronger than the efficiency of this
      prevention measure. This aim of the present study is to show by a placebo randomized study
      that 2g of Ceftriaxone within 8 hours post-intubation after a brain injury decrease the risk
      of occurence an early VAP.

      Ancillary study An ancillary study is performed in 2 centres which routinely practice rectal
      swabs at admission and discharge of ICU, to survey intestinal flora (CHU of Angers and CHU of
      Rennes). The goal of this study is to compare the incidence of acquired cephalosporin
      resistant gram negative bacteria at the discharge of ICU between the 2 groups of patients,
      receiving or not ceftriaxone.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Incidence of early VAP, proportion of patients who develop a VAP within the 7 first day after mechanical ventilation (the 7th day included), confirm with microbiological culture, within all included patients.
time frame: 30 months
measure: - Incidence of late VAP (> 7 jours)
time frame: 30 months
measure: - Global incidence of VAP during intensive care period (limited to day 60)
time frame: 30 months
measure: - Type of bacteria and their sensitivity for early or late VAP,
time frame: 30 months
measure: - Time between inclusion and occurence of the first VAP (limited to day 28),
time frame: 30 months
measure: - Length of the first period of mechanical ventilation during the intensive care period,
time frame: 30 months
measure: - Time between inclusion and the first spontaneous ventilation test (limited to day 28),
time frame: 30 months
measure: - Length of antibiotherapy during intensive care period,
time frame: 30 months
measure: - Length of intensive care, limited to 60 days,
time frame: 30 months
measure: - Length of stay in intensive care unit, limited to 60 days,
time frame: 30 months
measure: - Length of stay at the hospital, limited to 60 days,
time frame: 30 months
measure: - Neurological prognosis at the discharge of the intensive care unit,
time frame: 30 months
measure: - Mortality at day 28 and 60.
time frame: 30 months
measure: - Incidence of ventilated associated event (limited to day 60)
time frame: 30 months
measure: - Comparison of the global incidence of VAP according to the diagnosis defined by "American Thoracic Society" or by "Centers for Disease Control"
time frame: 30 months
arm group label: Ceftriaxone
arm group type: Experimental
arm group label: Sodium Chloride
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Anti-Infective Agents
arm group label: Ceftriaxone
intervention type: Drug
intervention name: Placebo
arm group label: Sodium Chloride
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Pneumonia
mesh term: Anti-Infective Agents