<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/NCT01734525</url>
  </required_header>
  <id_info>
    <org_study_id>Early Therapy</org_study_id>
    <nct_id>NCT01734525</nct_id>
  </id_info>
  <brief_title>Negative Beta Glucan in ICU Patients</brief_title>
  <official_title>A Pilot Study for the Use of Biomarkers and Early Treatment of Invasive Candidiasis in ICU Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidade Federal do Rio de Janeiro</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universidade Federal do Rio de Janeiro</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective study aimed at testing a strategy of early initiation of an antifungal&#xD;
      agent to patients admitted to intensive care units (ICUs) at risk for invasive candidiasis.&#xD;
      Score system have been developed to identify groups at very high risk for the development of&#xD;
      candidemia/invasive candidiasis in the ICU. These scoring system have used clinical&#xD;
      information with or without data on Candida colonization, and have shown reasonable&#xD;
      correlation with candidemia/invasive candidiasis. More recently, a biomarker - detection of&#xD;
      1,3-beta-D-glucan in the serum - has been tested in the early diagnosis of candidiasis. The&#xD;
      incorporation of biomarkers such as beta-D-glucan could help clinicians to select a group at&#xD;
      higher risk for candidemia, and despite the fact that these tests may give false-positive&#xD;
      results, their negative predictive value could be of great help.&#xD;
&#xD;
      Therefore, the objectives of this study are:&#xD;
&#xD;
        1. To assess the frequency of positive biomarkers in ICU patients at high risk to develop&#xD;
           invasive candidiasis/candidemia;&#xD;
&#xD;
        2. To test the strategy of early discontinuation of antifungal therapy based on repeatedly&#xD;
           negative blood cultures and 1,3 beta-D-glucan in the serum.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Entry criteria are: In the ICU for &gt;2 days AND systemic antibiotics &gt;2 days OR central venous&#xD;
      catheter for &gt;days AND at least two of the following: total parenteral nutrition, dialysis,&#xD;
      surgery, pancreatitis, receipt of corticosteroids, receipt of other immunosuppressive agents.&#xD;
      In addition, patients must have a clinical sign of infection (either one of the following):&#xD;
      fever, hypothermia, hypotension, unexplained acidosis, or unexplained elevation in C-reactive&#xD;
      protein.&#xD;
&#xD;
      Eligible patients will be enrolled after signing an informed consent and will have blood&#xD;
      obtained for culture and determination of 1,3 beta-D-glucan serum levels for 3 days, and will&#xD;
      start anidulafungin IV.&#xD;
&#xD;
      If all tests are negative, anidulafungin will be discontinued on day 4. If 1,3 beta-D-glucan&#xD;
      is positive (&gt;80 pg/ml) and / or blood cultures are positive for Candida species,&#xD;
      anidulafungin will be continued for &gt;14 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">December 2013</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluate the Ocurrence of Candidemia in Patients With Negative 1,3 Beta-D-glucan Who Discontinue Anidulafungin</measure>
    <time_frame>30 days</time_frame>
    <description>The main interest is to evaluate the ocurrence of candidemia in patients with negative 1,3 beta-D-glucan who discontinue anidulafungin</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">85</enrollment>
  <condition>Candidemia</condition>
  <arm_group>
    <arm_group_label>Anidulafungin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients at risk will receive therapy with anidulafungin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anidulafungin</intervention_name>
    <description>Anidulafungin at a dose of 200 mg in the first day and 100 mg daily afterwards</description>
    <arm_group_label>Anidulafungin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  In the ICU for &gt;2 days AND&#xD;
&#xD;
               -  Systemic antibiotics on days 1-3 of ICU OR&#xD;
&#xD;
               -  Central venous catheter on days 1-3 of ICU&#xD;
&#xD;
          -  AND at least 2 of:&#xD;
&#xD;
               -  Total parenteral nutrition on days 1-3 of ICU&#xD;
&#xD;
               -  Any dialysis on days 1-3 of ICU&#xD;
&#xD;
               -  Major surgery in the 7 days before admission in the ICU&#xD;
&#xD;
               -  Pancreatitis in the 7 days before admission in the ICU&#xD;
&#xD;
               -  Use of corticosteroids for at least 3 days in the 7 days before admission&#xD;
&#xD;
               -  Use of other immunosuppressive agents in the 7 days before admission in the ICU&#xD;
&#xD;
          -  In addition, the patient must have at least one of the following:&#xD;
&#xD;
               -  Fever (axillary temperature &gt;37.5 oC)&#xD;
&#xD;
               -  Hypothermia (axillary temperature &lt;35 oC)&#xD;
&#xD;
               -  Hypotension&#xD;
&#xD;
               -  Unexplained acidosis&#xD;
&#xD;
               -  Unexplained elevation in C-reactive protein&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Antifungal for &gt;3 days&#xD;
&#xD;
          -  Allergy to an echinocandin&#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>Marcio Nucci, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Universidade Federal do Rio de Janeiro</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Federal University of Rio de Janeiro</name>
      <address>
        <city>Rio de Janeiro</city>
        <state>RJ</state>
        <zip>21941913</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>November 20, 2012</study_first_submitted>
  <study_first_submitted_qc>November 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 27, 2012</study_first_posted>
  <results_first_submitted>November 30, 2015</results_first_submitted>
  <results_first_submitted_qc>April 18, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">July 8, 2019</results_first_posted>
  <last_update_submitted>April 18, 2019</last_update_submitted>
  <last_update_submitted_qc>April 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universidade Federal do Rio de Janeiro</investigator_affiliation>
    <investigator_full_name>Marcio Nucci</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>candidemia</keyword>
  <keyword>intensive care unit</keyword>
  <keyword>1,3 beta-D-glucan</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Candidemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anidulafungin</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Anidulafungin</title>
          <description>Patients at risk will receive therapy with anidulafungin&#xD;
Anidulafungin: Anidulafungin at a dose of 200 mg in the first day and 100 mg daily afterwards</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="85"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="85"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Anidulafungin</title>
          <description>Patients at risk will receive therapy with anidulafungin&#xD;
Anidulafungin: Anidulafungin at a dose of 200 mg in the first day and 100 mg daily afterwards</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="85"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63" lower_limit="22" upper_limit="87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="44"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Brazil</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Evaluate the Ocurrence of Candidemia in Patients With Negative 1,3 Beta-D-glucan Who Discontinue Anidulafungin</title>
        <description>The main interest is to evaluate the ocurrence of candidemia in patients with negative 1,3 beta-D-glucan who discontinue anidulafungin</description>
        <time_frame>30 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Anidulafungin</title>
            <description>Patients at risk will receive therapy with anidulafungin&#xD;
Anidulafungin: Anidulafungin at a dose of 200 mg in the first day and 100 mg daily afterwards</description>
          </group>
        </group_list>
        <measure>
          <title>Evaluate the Ocurrence of Candidemia in Patients With Negative 1,3 Beta-D-glucan Who Discontinue Anidulafungin</title>
          <description>The main interest is to evaluate the ocurrence of candidemia in patients with negative 1,3 beta-D-glucan who discontinue anidulafungin</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Candidemia</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No candidemia</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>One Arm</title>
          <description>Patients at risk will receive therapy with anidulafungin&#xD;
Anidulafungin: Anidulafungin at a dose of 200 mg in the first day and 100 mg daily afterwards</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="85"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Marcio Nucci</name_or_title>
      <organization>Federal University of Rio de Janeiro</organization>
      <phone>5521-39382463</phone>
      <email>mnucci@hucff.ufrj.br</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01734525
org study id: Early Therapy
nct id: NCT01734525
lead sponsor: 
has dmc: No
This is a prospective study aimed at testing a strategy of early initiation of an antifungal
      agent to patients admitted to intensive care units (ICUs) at risk for invasive candidiasis.
      Score system have been developed to identify groups at very high risk for the development of
      candidemia/invasive candidiasis in the ICU. These scoring system have used clinical
      information with or without data on Candida colonization, and have shown reasonable
      correlation with candidemia/invasive candidiasis. More recently, a biomarker - detection of
      1,3-beta-D-glucan in the serum - has been tested in the early diagnosis of candidiasis. The
      incorporation of biomarkers such as beta-D-glucan could help clinicians to select a group at
      higher risk for candidemia, and despite the fact that these tests may give false-positive
      results, their negative predictive value could be of great help.

      Therefore, the objectives of this study are:

        1. To assess the frequency of positive biomarkers in ICU patients at high risk to develop
           invasive candidiasis/candidemia;

        2. To test the strategy of early discontinuation of antifungal therapy based on repeatedly
           negative blood cultures and 1,3 beta-D-glucan in the serum.
Entry criteria are: In the ICU for >2 days AND systemic antibiotics >2 days OR central venous
      catheter for >days AND at least two of the following: total parenteral nutrition, dialysis,
      surgery, pancreatitis, receipt of corticosteroids, receipt of other immunosuppressive agents.
      In addition, patients must have a clinical sign of infection (either one of the following):
      fever, hypothermia, hypotension, unexplained acidosis, or unexplained elevation in C-reactive
      protein.

      Eligible patients will be enrolled after signing an informed consent and will have blood
      obtained for culture and determination of 1,3 beta-D-glucan serum levels for 3 days, and will
      start anidulafungin IV.

      If all tests are negative, anidulafungin will be discontinued on day 4. If 1,3 beta-D-glucan
      is positive (>80 pg/ml) and / or blood cultures are positive for Candida species,
      anidulafungin will be continued for >14 days.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Evaluate the Ocurrence of Candidemia in Patients With Negative 1,3 Beta-D-glucan Who Discontinue Anidulafungin
time frame: 30 days
description: The main interest is to evaluate the ocurrence of candidemia in patients with negative 1,3 beta-D-glucan who discontinue anidulafungin
arm group label: Anidulafungin
arm group type: Experimental
description: Patients at risk will receive therapy with anidulafungin
intervention type: Drug
intervention name: Anidulafungin
description: Anidulafungin at a dose of 200 mg in the first day and 100 mg daily afterwards
arm group label: Anidulafungin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marcio Nucci, MD
role: Study Chair
affiliation: Universidade Federal do Rio de Janeiro
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Universidade Federal do Rio de Janeiro
investigator full name: Marcio Nucci
investigator title: MD
mesh term: Candidemia
mesh term: Anidulafungin
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 