<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/NCT02225249</url>
  </required_header>
  <id_info>
    <org_study_id>250-14</org_study_id>
    <nct_id>NCT02225249</nct_id>
  </id_info>
  <brief_title>VASCULUX-examination of the Pulmonary VASCUlar Barrier in Patients During LUng Transplantation</brief_title>
  <acronym>VASCULUX</acronym>
  <official_title>Examination of the Pulmonary Vascular Barrier in Patients During Lung Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ludwig-Maximilians - University of Munich</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ludwig-Maximilians - University of Munich</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Lung transplantation is a well established method for surgical therapy for patients with end&#xD;
      stage pulmonary disease.&#xD;
&#xD;
      The investigators seek to determine to which extent the pulmonary vascular barrier gets&#xD;
      harmed during lung transplantation and whether pulmonary edema after reperfusion can be&#xD;
      monitored with measurement of extravascular lung water index (ELWI).&#xD;
&#xD;
      Additionally the investigaors are going to evaluate the correlation between ELWI and shedding&#xD;
      of the endothelial glycocalyx.&#xD;
&#xD;
      The study is designed as a prospective observational cohort study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is designed as a single center prospective observational cohort study including&#xD;
      only patients who are undergoing lung transplantation due to endstage pulmonary disease.&#xD;
&#xD;
      It is well known that pulmonary edema is one of the major problems following reperfusion of&#xD;
      the new organ.&#xD;
&#xD;
      The glycocalyx is located on the apical surface of vascular endothelial cells which line the&#xD;
      vascular lumen. The endothelial glycocalyx consists of mainly proteoglycans that covers,&#xD;
      among others, leukocyte and thrombocyte receptors and fulfills its principal role in&#xD;
      maintaining plasma and vessel wall homeostasis.&#xD;
&#xD;
      In patients undergoing cardiac surgery studies showed regional as well as global ischemia&#xD;
      causing an increase of syndecan-1 and heparansulphate in plasma during reperfusion.&#xD;
&#xD;
      The extent of the pulmonary vascular barrier's damage might serve as predictor for&#xD;
      postoperative complications as reperfusion edema of the lungs.&#xD;
&#xD;
      To quantify the extent of damage the investigators seek to evaluate the correlation between&#xD;
      ELWI and the damage to the vascular barrier. ELWI will be assessed using transpulmonary&#xD;
      thermodilution. Components of the vascular barrier will be quantified using ELISA-technique.&#xD;
      10 ml full blood will be drawn at 7 different predifined measurement points named T0-T7 as&#xD;
      follows:&#xD;
&#xD;
        -  T0 before induction of anesthesia&#xD;
&#xD;
        -  T1 before reperfusion of the first lung&#xD;
&#xD;
        -  T2 5 min after reperfusion of the first lung&#xD;
&#xD;
        -  T3 before reperfusion of the second lung&#xD;
&#xD;
        -  T4 5 min after reperfusion of the second lung&#xD;
&#xD;
        -  T5 before admission to the intensive care unit&#xD;
&#xD;
        -  T6 6h after reperfusion of the last lung&#xD;
&#xD;
        -  T7 12h after reperfusion of the last lung&#xD;
&#xD;
      For statistical analysis Student's t-test, Friedman or Wilcoxon rank test will be used, as&#xD;
      indicated.&#xD;
&#xD;
      Expected length of the study is 2 years enrolling 30 patients undergoing lung&#xD;
      transplantation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>October 2014</start_date>
  <completion_date type="Anticipated">July 2017</completion_date>
  <primary_completion_date type="Anticipated">October 2016</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>Components of the vascular barrier</measure>
    <time_frame>Repeated mesurements to detect differences from baseline values (T0).</time_frame>
    <description>Repeated measurements of each parameter to detect the difference from baseline values.&#xD;
Each component will be measured at time point: T0, T1, T2, T3, T4 and T5.&#xD;
Components to be measured [Unit]:&#xD;
Syndecan-1 [ng/ml]&#xD;
Hyaluronan [ng/ml]&#xD;
Heparan-Sulphate [ng/ml]&#xD;
Angiopoetin-1 [ng/ml]&#xD;
Angiopoetin-2 [ng/ml]&#xD;
Components getting measured using serum or plasma samples.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Extravascular Lung Water Index (ELWI)</measure>
    <time_frame>repeated measurement of ELWI to detect differences from baseline (T0)</time_frame>
    <description>Increase of the Extravascular Lung Water Index (ELWI) will be determined using thermodilution-method.&#xD;
Repeated measurement of ELWI to detect the difference from baseline values.&#xD;
Each component will be measured at time point: T0, T5, T6 and T7.&#xD;
Unit of measurement: [ml/kg]</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical parameters</measure>
    <time_frame>Repeated measurement of each parameter to detect differences from baseline (T0)</time_frame>
    <description>Follwowing clinicals parameters will be assessed at eacht time point to detect increases or decreases from baseline [Units]:&#xD;
Each parameter will be assessed at time point: T0, T1, T2, T3, T4, T5, T6, T7&#xD;
Oxygenation index [mmHg/FiO2]&#xD;
Heart rate [beats per min]&#xD;
Systolic blood pressure [mmHg]&#xD;
Mean arterial blood pressure [mmHg]&#xD;
Necessity of extracorporal lung assist [yes/no]&#xD;
The investigators assess clinical parameters as oxygenation index, heartrate, blood pressure.</description>
  </secondary_outcome>
  <enrollment type="Anticipated">30</enrollment>
  <condition>End Stage Chronic Obstructive Airways Disease</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples will be taken. In summary, 61.2 ml blood will be collected at 7 specific time&#xD;
      points.&#xD;
&#xD;
      Components of the vascular barrier are examined, in detail hyaluronan, syndecan-1, and&#xD;
      angiopoietin-2.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Eligible for this study are all patients being full of age and younger than 65 years&#xD;
        scheduled for lung transplantation&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  At least 18 and younger than 65 years of age&#xD;
&#xD;
          -  Scheduled for lung transplantation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Necessity of ECMO implementation before induction of general anesthesia&#xD;
&#xD;
          -  Mechanical ventilation before lung transplantation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dirk Bruegger, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical Faculty of Ludwig-Maximilians-University Munich</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Dirk Bruegger, MD</last_name>
    <phone>+4989440076414</phone>
    <email>dirk.bruegger@med.uni-muenchen.de</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Thomas Irlbeck, MD</last_name>
    <phone>+4989440073407</phone>
    <email>thomas.irlbeck@med.uni-muenchen.de</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University Hospital of Munich</name>
      <address>
        <city>Munich</city>
        <state>Bavaria</state>
        <zip>81377</zip>
        <country>Germany</country>
      </address>
    </facility>
    <contact>
      <last_name>Dirk Bruegger, MD</last_name>
      <phone>+4989440076414</phone>
      <email>dirk.bruegger@med.uni-muenchen.de</email>
    </contact>
    <investigator>
      <last_name>Dirk Bruegger, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 4, 2014</study_first_submitted>
  <study_first_submitted_qc>August 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 26, 2014</study_first_posted>
  <last_update_submitted>August 22, 2014</last_update_submitted>
  <last_update_submitted_qc>August 22, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 26, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ludwig-Maximilians - University of Munich</investigator_affiliation>
    <investigator_full_name>Dirk Bruegger MD</investigator_full_name>
    <investigator_title>PD Dr.</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</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/NCT02225249
org study id: 250-14
nct id: NCT02225249
lead sponsor: 
has dmc: No
Lung transplantation is a well established method for surgical therapy for patients with end
      stage pulmonary disease.

      The investigators seek to determine to which extent the pulmonary vascular barrier gets
      harmed during lung transplantation and whether pulmonary edema after reperfusion can be
      monitored with measurement of extravascular lung water index (ELWI).

      Additionally the investigaors are going to evaluate the correlation between ELWI and shedding
      of the endothelial glycocalyx.

      The study is designed as a prospective observational cohort study.
This study is designed as a single center prospective observational cohort study including
      only patients who are undergoing lung transplantation due to endstage pulmonary disease.

      It is well known that pulmonary edema is one of the major problems following reperfusion of
      the new organ.

      The glycocalyx is located on the apical surface of vascular endothelial cells which line the
      vascular lumen. The endothelial glycocalyx consists of mainly proteoglycans that covers,
      among others, leukocyte and thrombocyte receptors and fulfills its principal role in
      maintaining plasma and vessel wall homeostasis.

      In patients undergoing cardiac surgery studies showed regional as well as global ischemia
      causing an increase of syndecan-1 and heparansulphate in plasma during reperfusion.

      The extent of the pulmonary vascular barrier's damage might serve as predictor for
      postoperative complications as reperfusion edema of the lungs.

      To quantify the extent of damage the investigators seek to evaluate the correlation between
      ELWI and the damage to the vascular barrier. ELWI will be assessed using transpulmonary
      thermodilution. Components of the vascular barrier will be quantified using ELISA-technique.
      10 ml full blood will be drawn at 7 different predifined measurement points named T0-T7 as
      follows:

        -  T0 before induction of anesthesia

        -  T1 before reperfusion of the first lung

        -  T2 5 min after reperfusion of the first lung

        -  T3 before reperfusion of the second lung

        -  T4 5 min after reperfusion of the second lung

        -  T5 before admission to the intensive care unit

        -  T6 6h after reperfusion of the last lung

        -  T7 12h after reperfusion of the last lung

      For statistical analysis Student's t-test, Friedman or Wilcoxon rank test will be used, as
      indicated.

      Expected length of the study is 2 years enrolling 30 patients undergoing lung
      transplantation.
observational model: Cohort
time perspective: Prospective
measure: Components of the vascular barrier
time frame: Repeated mesurements to detect differences from baseline values (T0).
description: Repeated measurements of each parameter to detect the difference from baseline values.
Each component will be measured at time point: T0, T1, T2, T3, T4 and T5.
Components to be measured [Unit]:
Syndecan-1 [ng/ml]
Hyaluronan [ng/ml]
Heparan-Sulphate [ng/ml]
Angiopoetin-1 [ng/ml]
Angiopoetin-2 [ng/ml]
Components getting measured using serum or plasma samples.
measure: Extravascular Lung Water Index (ELWI)
time frame: repeated measurement of ELWI to detect differences from baseline (T0)
description: Increase of the Extravascular Lung Water Index (ELWI) will be determined using thermodilution-method.
Repeated measurement of ELWI to detect the difference from baseline values.
Each component will be measured at time point: T0, T5, T6 and T7.
Unit of measurement: [ml/kg]
measure: Clinical parameters
time frame: Repeated measurement of each parameter to detect differences from baseline (T0)
description: Follwowing clinicals parameters will be assessed at eacht time point to detect increases or decreases from baseline [Units]:
Each parameter will be assessed at time point: T0, T1, T2, T3, T4, T5, T6, T7
Oxygenation index [mmHg/FiO2]
Heart rate [beats per min]
Systolic blood pressure [mmHg]
Mean arterial blood pressure [mmHg]
Necessity of extracorporal lung assist [yes/no]
The investigators assess clinical parameters as oxygenation index, heartrate, blood pressure.
Blood samples will be taken. In summary, 61.2 ml blood will be collected at 7 specific time
      points.

      Components of the vascular barrier are examined, in detail hyaluronan, syndecan-1, and
      angiopoietin-2.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Dirk Bruegger, MD
role: Principal Investigator
affiliation: Medical Faculty of Ludwig-Maximilians-University Munich
last name: Dirk Bruegger, MD
phone: +4989440076414
email: dirk.bruegger@med.uni-muenchen.de
last name: Thomas Irlbeck, MD
phone: +4989440073407
email: thomas.irlbeck@med.uni-muenchen.de
facility: 
contact: 
investigator: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: Ludwig-Maximilians - University of Munich
investigator full name: Dirk Bruegger MD
investigator title: PD Dr.
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive