<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/NCT03774316</url>
  </required_header>
  <id_info>
    <org_study_id>2017_32</org_study_id>
    <secondary_id>2017-A03113-50</secondary_id>
    <nct_id>NCT03774316</nct_id>
  </id_info>
  <brief_title>De-escalation - Antifungal Treatment Immunocompromised Patients</brief_title>
  <acronym>D-ATFIM</acronym>
  <official_title>De-escalation of Antifungal Treatment in Immunocompromised Critically Ill Patients With Suspected Invasive Candida Infection: Incidence, Associated Factors, and Safety</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Lille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </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>
      A small proportion of intensive care unit patients receiving antifungals have a proven&#xD;
      invasive fungal infection. However, antifungal treatment has side effects such as toxicity,&#xD;
      emergence of resistance, and high cost. Moreover, empirical antifungal treatment is still a&#xD;
      matter for debate in these patients. Our study aimed to determine the incidence, associated&#xD;
      factors, and safety of de-escalation of antifungals in immunocompromised critically ill&#xD;
      patients.&#xD;
&#xD;
      This prospective observational study is conducted in 14 ICU, during a 6 months period. All&#xD;
      immunocompromised patients hospitalized for &gt;5d and treated with antifungals for suspected or&#xD;
      proven invasive candida infection will be included De-escalation is defined as a reduction in&#xD;
      antifungal spectrum or stopping initial drugs within the 5 days following their initiation.&#xD;
      The three antifungals considered in this study are from the narrowest to the widest spectrum:&#xD;
      fluconazole, caspofungin and liposomal amphotericin B.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a retrospective and prospective observational multicenter study, aiming to determine&#xD;
      the incidence, and safety of antifungal de-escalation in immunocompromised patients, and also&#xD;
      factors associated with de-escalation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 28, 2019</start_date>
  <completion_date type="Anticipated">September 2023</completion_date>
  <primary_completion_date type="Anticipated">September 2023</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>Percentage of patients with de-escalation of antifungal treatment</measure>
    <time_frame>5 days following start of antifungal treatment</time_frame>
    <description>De-escalation is defined as a reduction in antifungal treatment spectrum (switch from echinocandines or Amphotericin B to Azoles) or stopping all antifungals within the 5 days following their initiation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Risk factors for de-escalation of antifungal therapy</measure>
    <time_frame>during the 5 days following start of antifungal</time_frame>
    <description>Clinical characteristics and conditions significantly associated with de-escalation by univariate analysis will be entered in a multiple regression model to determine those independently associated with de-escalation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of days free of mechanical ventilation</measure>
    <time_frame>until day 28 after start of antifungal treatment</time_frame>
    <description>days with no mechanical ventilation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of days free of antifungal treatment</measure>
    <time_frame>until day 28 after start of antifungal treatment</time_frame>
    <description>days with no antifungal treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of ICU stay</measure>
    <time_frame>until day 28 after start of antifungal treatment</time_frame>
    <description>days in the ICU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality</measure>
    <time_frame>until day 28 after start of antifungal treatment</time_frame>
    <description>mortality related to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients with reoccurrence of candidiasis</measure>
    <time_frame>until day 7 after stop of antifungal treatment</time_frame>
    <description>reccurrence of candidiasis is defined as a new episode after the end of antifungal treatment</description>
  </secondary_outcome>
  <enrollment type="Anticipated">296</enrollment>
  <condition>Invasive Fungal Disease</condition>
  <condition>Critical Illness</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Adults immunocompromised patients hospitalized in intensive care units (Age ≥18 years)&#xD;
&#xD;
        Immunosuppression is defined by:&#xD;
&#xD;
          -  long-term immunosuppressive therapy (&gt; 3 months) or high-dose corticosteroid therapy&#xD;
             (&gt; 0.5 mg / kg / day for at least 3 days)&#xD;
&#xD;
          -  Solid organ transplant&#xD;
&#xD;
          -  Solid cancer (active or in remission since &lt;5 years)&#xD;
&#xD;
          -  Malignant haemopathy&#xD;
&#xD;
          -  HIV infection with CD4 &lt;200&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults immunocompromised patients hospitalized in intensive care units&#xD;
&#xD;
          -  Predictable invasive mechanical ventilation duration &gt; 96h&#xD;
&#xD;
          -  Signed consent (by patient or its representative)&#xD;
&#xD;
          -  First antifungal treatment initiation in ICU for proven or suspected candida infection&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breast-feeding women.&#xD;
&#xD;
          -  Fungal infection other than invasive candida&#xD;
&#xD;
          -  Prophylactic antifungal treatment.&#xD;
&#xD;
          -  Lack of informed consent&#xD;
&#xD;
          -  Predictable mechanical ventilation duration less than 48 hours&#xD;
&#xD;
          -  Patients discharged from ICU before the 5th day after initiation of TAF&#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>03 20 44 44 95</phone>
    <phone_ext>+33</phone_ext>
    <email>saad.nseir@chru-lille.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>CHU Lille</name>
      <address>
        <city>Lille</city>
        <zip>59000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Saad Nseir, MD, PhD</last_name>
      <phone>33320444495</phone>
      <email>s-nseir@chru-lille.fr</email>
    </contact>
    <contact_backup>
      <last_name>Damia MEDDOUR, CRA</last_name>
      <email>damia.meddour@chru-lille.fr</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>December 3, 2018</study_first_submitted>
  <study_first_submitted_qc>December 11, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>October 14, 2022</last_update_submitted>
  <last_update_submitted_qc>October 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 17, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>De-escalation</keyword>
  <keyword>Antifungal treatment</keyword>
  <keyword>Mortality</keyword>
  <keyword>Immunocompromised</keyword>
  <keyword>Intensive care</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycoses</mesh_term>
    <mesh_term>Invasive Fungal Infections</mesh_term>
    <mesh_term>Critical Illness</mesh_term>
  </condition_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/NCT03774316
org study id: 2017_32
secondary id: 2017-A03113-50
nct id: NCT03774316
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A small proportion of intensive care unit patients receiving antifungals have a proven
      invasive fungal infection. However, antifungal treatment has side effects such as toxicity,
      emergence of resistance, and high cost. Moreover, empirical antifungal treatment is still a
      matter for debate in these patients. Our study aimed to determine the incidence, associated
      factors, and safety of de-escalation of antifungals in immunocompromised critically ill
      patients.

      This prospective observational study is conducted in 14 ICU, during a 6 months period. All
      immunocompromised patients hospitalized for >5d and treated with antifungals for suspected or
      proven invasive candida infection will be included De-escalation is defined as a reduction in
      antifungal spectrum or stopping initial drugs within the 5 days following their initiation.
      The three antifungals considered in this study are from the narrowest to the widest spectrum:
      fluconazole, caspofungin and liposomal amphotericin B.
This is a retrospective and prospective observational multicenter study, aiming to determine
      the incidence, and safety of antifungal de-escalation in immunocompromised patients, and also
      factors associated with de-escalation.
observational model: Cohort
time perspective: Prospective
measure: Percentage of patients with de-escalation of antifungal treatment
time frame: 5 days following start of antifungal treatment
description: De-escalation is defined as a reduction in antifungal treatment spectrum (switch from echinocandines or Amphotericin B to Azoles) or stopping all antifungals within the 5 days following their initiation
measure: Risk factors for de-escalation of antifungal therapy
time frame: during the 5 days following start of antifungal
description: Clinical characteristics and conditions significantly associated with de-escalation by univariate analysis will be entered in a multiple regression model to determine those independently associated with de-escalation
measure: Number of days free of mechanical ventilation
time frame: until day 28 after start of antifungal treatment
description: days with no mechanical ventilation
measure: Number of days free of antifungal treatment
time frame: until day 28 after start of antifungal treatment
description: days with no antifungal treatment
measure: Length of ICU stay
time frame: until day 28 after start of antifungal treatment
description: days in the ICU
measure: All-cause mortality
time frame: until day 28 after start of antifungal treatment
description: mortality related to any cause
measure: Percentage of patients with reoccurrence of candidiasis
time frame: until day 7 after stop of antifungal treatment
description: reccurrence of candidiasis is defined as a new episode after the end of antifungal treatment
study pop: 
sampling method: Non-Probability Sample
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: 03 20 44 44 95
phone ext: +33
email: saad.nseir@chru-lille.fr
facility: 
status: Recruiting
contact: 
contact backup: 
country: France
responsible party type: Sponsor
mesh term: Mycoses
mesh term: Invasive Fungal Infections
mesh term: Critical Illness