<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/NCT03011424</url>
  </required_header>
  <id_info>
    <org_study_id>2013/149-31/2</org_study_id>
    <nct_id>NCT03011424</nct_id>
  </id_info>
  <brief_title>Early Postoperative Extracorporal Liver Support Therapy (ELS) as a Tool to Manage Post Hepatectomy Liver Failure (PLF)</brief_title>
  <official_title>Early Postoperative Extracorporal Liver Support Therapy (ELS) as a Tool to Manage Post Hepatectomy Liver Failure (PLF)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Karolinska University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Karolinska University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Early postoperative extracorporal liver support therapy (ELS) as a tool to manage post&#xD;
      hepatectomy liver failure (PLF).&#xD;
&#xD;
      Post-operative liver failure (PLF) has been identified as a major risk factor leading to&#xD;
      increased morbidity and mortality. The incidence of PLF varies largely between 0-30%, and may&#xD;
      be accounted for the main reason of postoperative mortality related to liver surgery&#xD;
      (reported figures ranging from 18 to 75 %).&#xD;
&#xD;
      Currently, there are only a few treatment options for PLF, mainly restricted to the treatment&#xD;
      of complications like bile leakage, infections as well as the prevention of further liver&#xD;
      damage caused by e.g. thrombosis or haemorrhage as well as administration of liver toxic&#xD;
      drugs. Recently the international study group on liver surgery (ISGLS) published criteria for&#xD;
      a new definition of PLF which will greatly facilitate the comparison of results from future&#xD;
      studies on a variety of aspects on liver failure.&#xD;
&#xD;
      ELS by using the Molecular Adsorbent Recirculating System (MARS) is based on a modified&#xD;
      haemodialysis that allows the removal of water-soluble and protein bound toxins over an&#xD;
      albumin-coated high flux membrane against recycled exogenous albumin. Thus, MARS can support&#xD;
      the compromised detoxification capacity of the liver as well as improve physiological&#xD;
      parameters. This would offer the potential for temporary support for the harmed liver after&#xD;
      liver resection allowing for a more uneventful recovery.&#xD;
&#xD;
      For obvious reasons previous reports contain few patients, present heterogonous treatment&#xD;
      groups and all suffer from lack of standardized treatment protocols. Few if any surviving&#xD;
      patients, thus providing no evidence to encourage ELS as a possible treatment option for&#xD;
      patients suffering of PLF. However, studies with defined patient populations and treatments&#xD;
      according to a predefined standardised treatment protocol are warranted.&#xD;
&#xD;
      Primary issues to be addressed:&#xD;
&#xD;
        1. Can ELS be applied in an early phase of PLF?&#xD;
&#xD;
        2. Is ELS safe and feasible for the treatment of PLF when practised according to a&#xD;
           predefined protocol?&#xD;
&#xD;
      Secondary issues to be addressed:&#xD;
&#xD;
        1. The development of predictive laboratory-chemical markers of liver failure&#xD;
&#xD;
        2. Indirect measures of portal flow and portal pressure&#xD;
&#xD;
        3. Indocyanine green clearance (ICG) under ELS treatment&#xD;
&#xD;
        4. Clearance of toxic products as assessed in aliquots taken from the dialysate&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary issues to be addressed&#xD;
&#xD;
        1. Can ELS be applied in an early phase of PLF?&#xD;
&#xD;
        2. Is ELS safe and feasible for the treatment of PLF when practised according to a&#xD;
           predefined protocol?&#xD;
&#xD;
      Secondary issues to be addressed&#xD;
&#xD;
        1. The development of predictive laboratory-chemical markers of liver failure&#xD;
&#xD;
        2. Indirect measures of portal flow and portal pressure&#xD;
&#xD;
        3. Indocyanine green clearance (ICG) under ELS treatment&#xD;
&#xD;
        4. Clearance of toxic products as assessed in aliquots taken from the dialysate&#xD;
&#xD;
      Design&#xD;
&#xD;
        -  Prospective phase 1 safety and feasibility study&#xD;
&#xD;
      Study Population&#xD;
&#xD;
        -  10 consecutive patients being subjected to extended liver surgery (at least right sided&#xD;
           or extended right/left sided hemihepatectomy)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2013</start_date>
  <completion_date type="Actual">November 2015</completion_date>
  <primary_completion_date type="Actual">May 2015</primary_completion_date>
  <phase>N/A</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>Number of PLF patients who develop serious adverse events during ELS according to SOFA scores and Westhaven criteria</measure>
    <time_frame>First two weeks postoperatively after major hepatectomy</time_frame>
    <description>At least five sessions of Mars. SOFA (score 1-4).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of PLF patients who develop serious adverse events during ELS</measure>
    <time_frame>First two weeks postoperatively after major hepatectomy</time_frame>
    <description>At least five sessions of Mars. Westhaven (criteria 1-4)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The predictive value of liver enzymes and bilirubin changes as marker of liver failure</measure>
    <time_frame>First two weeks postoperatively after major hepatectomy</time_frame>
    <description>At least five sessions of Mars. Liver enzymes measured( liver transaminases microkat/L ), bilirubin (mmol/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Portal flow (ml/minute) before and during ELS</measure>
    <time_frame>First two weeks postoperatively after major hepatectomy</time_frame>
    <description>At least five sessions of Mars</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess liver function by use of Indocyanine green clearance (ICG)(% clearance/unit time) under ELS treatment</measure>
    <time_frame>First two weeks postoperatively after major hepatectomy</time_frame>
    <description>At least five sessions of Mars</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Portal pressure (cmH2O) before and during ELS</measure>
    <time_frame>First two weeks postoperatively after major hepatectomy</time_frame>
    <description>At least five sessions of Mars</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Post Hepatectomy Liver Failure</condition>
  <arm_group>
    <arm_group_label>Early Postoperative Extracorporal Liver Support Therapy (ELS)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Early Postoperative Extracorporal Liver Support Therapy (ELS) by using the Molecular Adsorbent Recirculating System (MARS)</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Extracorporeal liver support therapy (ELS)</intervention_name>
    <description>ELS by using the Molecular Adsorbent Recirculating System (MARS) is based on a modified haemodialysis that allows the removal of water-soluble and protein bound toxins over an albumin-coated high flux membrane against recycled exogenous albumin.</description>
    <arm_group_label>Early Postoperative Extracorporal Liver Support Therapy (ELS)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age between 18 and 70 years&#xD;
&#xD;
          -  Patients subjected for major liver surgery (4 or more Couinaud segments, ca. 50 % or&#xD;
             more of total liver volume)&#xD;
&#xD;
          -  Pre-operative chemotherapy and/or biological agents are allowed&#xD;
&#xD;
          -  Liver cirrhosis Child Pugh Score A is allowed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any contra indication for ELS such as uncontrolled active bleeding or platelet counts&#xD;
             &lt;20.000 /µl&#xD;
&#xD;
          -  Macroscopic liver cirrhosis (Child Pugh Score B and C)&#xD;
&#xD;
          -  Inability or unwilling to give informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bengt Isaksson, Ass prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Karolinska Institutet</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Surgery Gastrocentrum Karolinska Univeristy Hospital</name>
      <address>
        <city>Stockholm</city>
        <zip>14186</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>October 24, 2016</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <last_update_submitted>January 2, 2019</last_update_submitted>
  <last_update_submitted_qc>January 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 4, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Karolinska University Hospital</investigator_affiliation>
    <investigator_full_name>Lars Lundell</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Liver resection</keyword>
  <keyword>post hepatectomy liver failure</keyword>
  <keyword>liver dialysis</keyword>
  <keyword>encephalopathy</keyword>
  <keyword>mortality</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Failure</mesh_term>
    <mesh_term>Hepatic Insufficiency</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Publication in peer reviewed journal</ipd_description>
  </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/NCT03011424
org study id: 2013/149-31/2
nct id: NCT03011424
lead sponsor: 
has dmc: No
Early postoperative extracorporal liver support therapy (ELS) as a tool to manage post
      hepatectomy liver failure (PLF).

      Post-operative liver failure (PLF) has been identified as a major risk factor leading to
      increased morbidity and mortality. The incidence of PLF varies largely between 0-30%, and may
      be accounted for the main reason of postoperative mortality related to liver surgery
      (reported figures ranging from 18 to 75 %).

      Currently, there are only a few treatment options for PLF, mainly restricted to the treatment
      of complications like bile leakage, infections as well as the prevention of further liver
      damage caused by e.g. thrombosis or haemorrhage as well as administration of liver toxic
      drugs. Recently the international study group on liver surgery (ISGLS) published criteria for
      a new definition of PLF which will greatly facilitate the comparison of results from future
      studies on a variety of aspects on liver failure.

      ELS by using the Molecular Adsorbent Recirculating System (MARS) is based on a modified
      haemodialysis that allows the removal of water-soluble and protein bound toxins over an
      albumin-coated high flux membrane against recycled exogenous albumin. Thus, MARS can support
      the compromised detoxification capacity of the liver as well as improve physiological
      parameters. This would offer the potential for temporary support for the harmed liver after
      liver resection allowing for a more uneventful recovery.

      For obvious reasons previous reports contain few patients, present heterogonous treatment
      groups and all suffer from lack of standardized treatment protocols. Few if any surviving
      patients, thus providing no evidence to encourage ELS as a possible treatment option for
      patients suffering of PLF. However, studies with defined patient populations and treatments
      according to a predefined standardised treatment protocol are warranted.

      Primary issues to be addressed:

        1. Can ELS be applied in an early phase of PLF?

        2. Is ELS safe and feasible for the treatment of PLF when practised according to a
           predefined protocol?

      Secondary issues to be addressed:

        1. The development of predictive laboratory-chemical markers of liver failure

        2. Indirect measures of portal flow and portal pressure

        3. Indocyanine green clearance (ICG) under ELS treatment

        4. Clearance of toxic products as assessed in aliquots taken from the dialysate
Primary issues to be addressed

        1. Can ELS be applied in an early phase of PLF?

        2. Is ELS safe and feasible for the treatment of PLF when practised according to a
           predefined protocol?

      Secondary issues to be addressed

        1. The development of predictive laboratory-chemical markers of liver failure

        2. Indirect measures of portal flow and portal pressure

        3. Indocyanine green clearance (ICG) under ELS treatment

        4. Clearance of toxic products as assessed in aliquots taken from the dialysate

      Design

        -  Prospective phase 1 safety and feasibility study

      Study Population

        -  10 consecutive patients being subjected to extended liver surgery (at least right sided
           or extended right/left sided hemihepatectomy)
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of PLF patients who develop serious adverse events during ELS according to SOFA scores and Westhaven criteria
time frame: First two weeks postoperatively after major hepatectomy
description: At least five sessions of Mars. SOFA (score 1-4).
measure: Number of PLF patients who develop serious adverse events during ELS
time frame: First two weeks postoperatively after major hepatectomy
description: At least five sessions of Mars. Westhaven (criteria 1-4)
measure: The predictive value of liver enzymes and bilirubin changes as marker of liver failure
time frame: First two weeks postoperatively after major hepatectomy
description: At least five sessions of Mars. Liver enzymes measured( liver transaminases microkat/L ), bilirubin (mmol/L)
measure: Portal flow (ml/minute) before and during ELS
time frame: First two weeks postoperatively after major hepatectomy
description: At least five sessions of Mars
measure: To assess liver function by use of Indocyanine green clearance (ICG)(% clearance/unit time) under ELS treatment
time frame: First two weeks postoperatively after major hepatectomy
description: At least five sessions of Mars
measure: Portal pressure (cmH2O) before and during ELS
time frame: First two weeks postoperatively after major hepatectomy
description: At least five sessions of Mars
arm group label: Early Postoperative Extracorporal Liver Support Therapy (ELS)
arm group type: Experimental
description: Early Postoperative Extracorporal Liver Support Therapy (ELS) by using the Molecular Adsorbent Recirculating System (MARS)
intervention type: Device
intervention name: Extracorporeal liver support therapy (ELS)
description: ELS by using the Molecular Adsorbent Recirculating System (MARS) is based on a modified haemodialysis that allows the removal of water-soluble and protein bound toxins over an albumin-coated high flux membrane against recycled exogenous albumin.
arm group label: Early Postoperative Extracorporal Liver Support Therapy (ELS)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Bengt Isaksson, Ass prof
role: Principal Investigator
affiliation: Karolinska Institutet
facility: 
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Karolinska University Hospital
investigator full name: Lars Lundell
investigator title: Professor
mesh term: Liver Failure
mesh term: Hepatic Insufficiency
sharing ipd: Yes
ipd description: Publication in peer reviewed journal