<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/NCT03262558</url>
  </required_header>
  <id_info>
    <org_study_id>35RC16_9886</org_study_id>
    <nct_id>NCT03262558</nct_id>
  </id_info>
  <brief_title>Mediastinitis and Staphylococcus Aureus</brief_title>
  <acronym>MEDIASTAPH</acronym>
  <official_title>Immunological and Bacteriological Approaches to the Development of Postoperative Mediastinitis With Staphylococcus Aureus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rennes University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rennes University Hospital</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>
      Cardiac surgery with extracorporeal circulation (ECC) yields a deep immune system dysfunction&#xD;
      that exposes patients to postoperative infectious complications. Among these, post-operative&#xD;
      mediastinitis with Staphylococcus aureus (SA) generates significant morbidity and mortality.&#xD;
      Two radically different approaches have been proposed in recent years to reduce the incidence&#xD;
      of this complication. A first approach has attempted, without real success, to decrease&#xD;
      postoperative immunosuppression. The second, more efficient, consisted of screening and&#xD;
      preoperatively treating patients colonized with SA. However, although its incidence has&#xD;
      decreased, postoperative mediastinitis remains a terrible nosocomial infection. The authors&#xD;
      believe that a thorough analysis of the immunological changes induced by cardiac surgery will&#xD;
      initiate active therapeutics to reduce the post-operative immunosuppression phase, thereby&#xD;
      decreasing the risk of nosocomial infections. In addition, a study of the interactions&#xD;
      between the operated (host) and staphylococcus aureus (pathogenic) immune systems will&#xD;
      provide a better understanding of the mechanisms that expose patients to this bacterium.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In particular, changes induced by the ECC will be evaluated on:&#xD;
&#xD;
        -  Indoleamine 2,3-dioxygenase activity (IDO)&#xD;
&#xD;
        -  Apoptosis of lymphocytes and dendritic cells&#xD;
&#xD;
        -  Polymorphonuclear neutrophils (PMNs)&#xD;
&#xD;
        -  Myeloid Derived Suppressor Cells (MDSC )&#xD;
&#xD;
      After general anesthesia and arterial catheterization and prior to the start of ECC, blood&#xD;
      samples will be taken for flow cytometry studies, for the purification of PMNs and monocytes.&#xD;
      The purified PMNs and monocytes will then be used for the measurement of cytokine,&#xD;
      phagocytosis and bactericidal production capacities.&#xD;
&#xD;
      The morning following surgery, blood samples will be taken and follow the same process.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 4, 2016</start_date>
  <completion_date type="Actual">September 29, 2019</completion_date>
  <primary_completion_date type="Actual">July 1, 2017</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>Variation of plasma IDO activity</measure>
    <time_frame>Baseline and the morning following surgery</time_frame>
    <description>IDO activity is evaluated by the Kynurenin / Tryptophan ratio before and after ECC.&#xD;
Enzymatic activities will be measured by high performance liquid chromatography (HPLC) on pre- and post-operative blood tests</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Variation of phagocytosis capacity of PMNs</measure>
    <time_frame>Baseline and the morning following surgery</time_frame>
    <description>Comparison before and after ECC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variation of bactericidal capacity of PMNs</measure>
    <time_frame>Baseline and the morning following surgery</time_frame>
    <description>Comparison before and after ECC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variation of phagocytosis capacity of macrophages</measure>
    <time_frame>Baseline and the morning following surgery</time_frame>
    <description>Comparison before and after ECC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variation of bactericidal capacity of macrophages</measure>
    <time_frame>Baseline and the morning following surgery</time_frame>
    <description>Comparison before and after ECC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of an inhibitor of IDO on phagocytosis capacities of PMNs</measure>
    <time_frame>The day following surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of an inhibitor of IDO on bactericidal capacities of PMNs</measure>
    <time_frame>The day following surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of an inhibitor of IDO on phagocytosis capacities of macrophages</measure>
    <time_frame>The day following surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of an inhibitor of IDO on bactericidal capacities of macrophages</measure>
    <time_frame>The day following surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantification of lymphocytic apoptosis before and after the ECC</measure>
    <time_frame>Baseline and the morning following surgery</time_frame>
    <description>Quantification of apoptosis by flow cytometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantification of lymphocytic apoptosis in the presence of an inhibitor of IDO</measure>
    <time_frame>The day following surgery</time_frame>
    <description>Quantification of apoptosis by flow cytometry</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">27</enrollment>
  <condition>Surgery, Cardiac</condition>
  <condition>Infection</condition>
  <arm_group>
    <arm_group_label>Patients with ECC</arm_group_label>
    <description>No intervention</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No intervention</intervention_name>
    <description>Patients will undergo standard clinical routine practice in this indication</description>
    <arm_group_label>Patients with ECC</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients in the aftermath of an ECC for cardiac surgery are investigated to look for the&#xD;
        origin of a hypo-reactivity of PMNs and macrophages during exposure to staphylococcus&#xD;
        aureus&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          -  Patients over 18 years of age&#xD;
&#xD;
          -  Patients who require cardiac surgery (valvular and / or coronary) with extracorporeal&#xD;
             circulation.&#xD;
&#xD;
        Non inclusion criteria&#xD;
&#xD;
          -  Chronic respiratory diseases,&#xD;
&#xD;
          -  Preoperative left ventricular dysfunction (LVEF &lt;50%),&#xD;
&#xD;
          -  Immunosuppression (HIV infection, systemic corticosteroid therapy, history of cancer&#xD;
             in the year before surgery),&#xD;
&#xD;
          -  Persons subject to legal protection (safeguard of justice, curatorship, guardianship),&#xD;
&#xD;
          -  Persons deprived of liberty.&#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>Jean-Marc TADIE, Md, PhD</last_name>
    <role>Study Director</role>
    <affiliation>CHU Rennes</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rennes Hospital University</name>
      <address>
        <city>Rennes</city>
        <zip>35033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>August 22, 2017</study_first_submitted>
  <study_first_submitted_qc>August 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 25, 2017</study_first_posted>
  <last_update_submitted>December 13, 2022</last_update_submitted>
  <last_update_submitted_qc>December 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>staphylococcus aureus</keyword>
  <keyword>nosocomial infection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mediastinitis</mesh_term>
  </condition_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/NCT03262558
org study id: 35RC16_9886
nct id: NCT03262558
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Cardiac surgery with extracorporeal circulation (ECC) yields a deep immune system dysfunction
      that exposes patients to postoperative infectious complications. Among these, post-operative
      mediastinitis with Staphylococcus aureus (SA) generates significant morbidity and mortality.
      Two radically different approaches have been proposed in recent years to reduce the incidence
      of this complication. A first approach has attempted, without real success, to decrease
      postoperative immunosuppression. The second, more efficient, consisted of screening and
      preoperatively treating patients colonized with SA. However, although its incidence has
      decreased, postoperative mediastinitis remains a terrible nosocomial infection. The authors
      believe that a thorough analysis of the immunological changes induced by cardiac surgery will
      initiate active therapeutics to reduce the post-operative immunosuppression phase, thereby
      decreasing the risk of nosocomial infections. In addition, a study of the interactions
      between the operated (host) and staphylococcus aureus (pathogenic) immune systems will
      provide a better understanding of the mechanisms that expose patients to this bacterium.
In particular, changes induced by the ECC will be evaluated on:

        -  Indoleamine 2,3-dioxygenase activity (IDO)

        -  Apoptosis of lymphocytes and dendritic cells

        -  Polymorphonuclear neutrophils (PMNs)

        -  Myeloid Derived Suppressor Cells (MDSC )

      After general anesthesia and arterial catheterization and prior to the start of ECC, blood
      samples will be taken for flow cytometry studies, for the purification of PMNs and monocytes.
      The purified PMNs and monocytes will then be used for the measurement of cytokine,
      phagocytosis and bactericidal production capacities.

      The morning following surgery, blood samples will be taken and follow the same process.
observational model: Cohort
time perspective: Prospective
measure: Variation of plasma IDO activity
time frame: Baseline and the morning following surgery
description: IDO activity is evaluated by the Kynurenin / Tryptophan ratio before and after ECC.
Enzymatic activities will be measured by high performance liquid chromatography (HPLC) on pre- and post-operative blood tests
measure: Variation of phagocytosis capacity of PMNs
time frame: Baseline and the morning following surgery
description: Comparison before and after ECC
measure: Variation of bactericidal capacity of PMNs
time frame: Baseline and the morning following surgery
description: Comparison before and after ECC
measure: Variation of phagocytosis capacity of macrophages
time frame: Baseline and the morning following surgery
description: Comparison before and after ECC
measure: Variation of bactericidal capacity of macrophages
time frame: Baseline and the morning following surgery
description: Comparison before and after ECC
measure: Effect of an inhibitor of IDO on phagocytosis capacities of PMNs
time frame: The day following surgery
measure: Effect of an inhibitor of IDO on bactericidal capacities of PMNs
time frame: The day following surgery
measure: Effect of an inhibitor of IDO on phagocytosis capacities of macrophages
time frame: The day following surgery
measure: Effect of an inhibitor of IDO on bactericidal capacities of macrophages
time frame: The day following surgery
measure: Quantification of lymphocytic apoptosis before and after the ECC
time frame: Baseline and the morning following surgery
description: Quantification of apoptosis by flow cytometry
measure: Quantification of lymphocytic apoptosis in the presence of an inhibitor of IDO
time frame: The day following surgery
description: Quantification of apoptosis by flow cytometry
arm group label: Patients with ECC
description: No intervention
intervention type: Other
intervention name: No intervention
description: Patients will undergo standard clinical routine practice in this indication
arm group label: Patients with ECC
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jean-Marc TADIE, Md, PhD
role: Study Director
affiliation: CHU Rennes
facility: 
country: France
responsible party type: Sponsor
mesh term: Mediastinitis
sharing ipd: No