<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/NCT02251041</url>
  </required_header>
  <id_info>
    <org_study_id>CAPITL RCT</org_study_id>
    <nct_id>NCT02251041</nct_id>
  </id_info>
  <brief_title>Combined Drug Approach to Prevent Ischemia-reperfusion Injury During Transplantation of Livers (CAPITL)</brief_title>
  <acronym>CAPITL</acronym>
  <official_title>Combined Drug Approach to Prevent Ischemia-reperfusion Injury During Transplantation of Livers (CAPITL): a First-in-men Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitaire Ziekenhuizen KU Leuven</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universitaire Ziekenhuizen KU Leuven</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to establish the effectiveness of the combined drug approach&#xD;
      (anti-thrombin III, infliximab, apotransferrin, human recombinant erythropoietin beta,&#xD;
      C1-inhibitor, glutathione, alfa-tocopherol, melatonin and epoprostenol)aimed to reduce&#xD;
      ischemia-reperfusion injury during liver transplantation in eligible recipients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Actual">August 2019</completion_date>
  <primary_completion_date type="Actual">February 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>log-transformed peak AST</measure>
    <time_frame>within 72 hours following liver transplantation</time_frame>
    <description>log-transformed peak AST, where peak AST is defined as the highest value of serum AST within 72 hours following liver transplantation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>graft loss</measure>
    <time_frame>3 and 12 months after liver transplantation</time_frame>
    <description>graft loss at 3 and 12 months after liver transplantation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>recipient death</measure>
    <time_frame>3 and 12 months after liver transplantation</time_frame>
    <description>recipient death at 3 and 12 months after liver transplantation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>early graft dysfunction</measure>
    <time_frame>within first 7 days</time_frame>
    <description>early graft dysfunction as defined by Olthoff</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of biliary strictures</measure>
    <time_frame>within 12 months post transplantation</time_frame>
    <description>Incidence of biliary strictures within 12 months post transplantation by MRCP (magentic resonance cholangiopancreatography)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>IRI score</measure>
    <time_frame>during transplantation, 1 week and 1 year after</time_frame>
    <description>IRI score during transplantation, 1 week and 1 year after liver transplantation by using the Suzuki score and Monbaliu et al.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Graft rejecton</measure>
    <time_frame>till 1 year after transplantation</time_frame>
    <description>a liver biopsy will be taken after transplantation and in cas of clinical suspicion of acute rejection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Surgical complications</measure>
    <time_frame>within 30 days after liver transplantation</time_frame>
    <description>the ranking of surgical complications will be done by using Clavien-Dindo classification</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>Reperfusion Injury</condition>
  <arm_group>
    <arm_group_label>cases</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>the group receives a combination of drugs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>controles</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>the group do not receive a combination of drugs, but a placebo (sodium chloride solution)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Antithrombin-III</intervention_name>
    <arm_group_label>cases</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Infliximab</intervention_name>
    <arm_group_label>cases</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apotransferrin</intervention_name>
    <arm_group_label>cases</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Human recombinant erythropoietin</intervention_name>
    <arm_group_label>cases</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>C1-Inhibitor</intervention_name>
    <arm_group_label>cases</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glutathione</intervention_name>
    <arm_group_label>cases</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alfa-tocopherol</intervention_name>
    <arm_group_label>cases</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melatonin</intervention_name>
    <arm_group_label>cases</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Epoprostenol</intervention_name>
    <arm_group_label>cases</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium chloride solution</intervention_name>
    <arm_group_label>controles</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients suffering from irreversible liver failure eligible for liver transplantation&#xD;
             according to Eurotransplant guidelines.&#xD;
&#xD;
          2. Patients &gt; 18 years of age at time of listing on Eurotransplant waiting list for liver&#xD;
             transplantation in University Hospitals Leuven, Belgium.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who refuse to participate in the study.&#xD;
&#xD;
          2. History of hypersensitivity to one/several component(s) of the combined drug approach.&#xD;
&#xD;
          3. Conditions that prevent the use of the combined drug approach:&#xD;
&#xD;
               -  Administration of heparin at therapeutic dose pre-operatively,&#xD;
&#xD;
               -  Congestive heart failure,&#xD;
&#xD;
               -  History of seizure, poorly controlled arterial hypertension, myocardial&#xD;
                  infarction or stroke in the month preceding the liver transplantation, venous&#xD;
                  thromboembolic disease,&#xD;
&#xD;
               -  Unstable angina pectoris,&#xD;
&#xD;
               -  Sepsis, abcesses or opportunistic infections,&#xD;
&#xD;
               -  History of infliximab treatment,&#xD;
&#xD;
               -  Use of vitamin K antagonist anticoagulation.&#xD;
&#xD;
          4. Mental conditions rendering the subject incapable to understand the nature, scope, and&#xD;
             consequences of the trial.&#xD;
&#xD;
          5. Combined organ transplantation.&#xD;
&#xD;
          6. Re-transplantation.&#xD;
&#xD;
          7. Patients that are dialysis-dependent prior to the liver transplantation.&#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>Diethard Monbaliu, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Abdominal transplant surgery - transplant coordination, Abdominal transplant surgery lab (microbiology &amp; immunology Dpt)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospitals Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <reference>
    <citation>Monbaliu D, Vekemans K, Hoekstra H, Vaahtera L, Libbrecht L, Derveaux K, Parkkinen J, Liu Q, Heedfeld V, Wylin T, Deckx H, Zeegers M, Balligand E, Buurman W, van Pelt J, Porte RJ, Pirenne J. Multifactorial biological modulation of warm ischemia reperfusion injury in liver transplantation from non-heart-beating donors eliminates primary nonfunction and reduces bile salt toxicity. Ann Surg. 2009 Nov;250(5):808-17. doi: 10.1097/SLA.0b013e3181bdd787.</citation>
    <PMID>19826248</PMID>
  </reference>
  <reference>
    <citation>Vekemans K, Monbaliu D, Balligand E, Heedfeld V, Jochmans I, Pirenne J, van Pelt J. Improving the function of liver grafts exposed to warm ischemia by the Leuven drug protocol: exploring the molecular basis by microarray. Liver Transpl. 2012 Feb;18(2):206-18. doi: 10.1002/lt.22446.</citation>
    <PMID>21987442</PMID>
  </reference>
  <verification_date>December 2015</verification_date>
  <study_first_submitted>September 24, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2014</study_first_posted>
  <last_update_submitted>August 8, 2019</last_update_submitted>
  <last_update_submitted_qc>August 8, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Liver</keyword>
  <keyword>Transplantation</keyword>
  <keyword>Ischemia-reperfusion</keyword>
  <keyword>Effectiveness</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Reperfusion Injury</mesh_term>
    <mesh_term>Ischemia</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tocopherols</mesh_term>
    <mesh_term>Vitamin E</mesh_term>
    <mesh_term>alpha-Tocopherol</mesh_term>
    <mesh_term>Infliximab</mesh_term>
    <mesh_term>Epoprostenol</mesh_term>
    <mesh_term>Tezosentan</mesh_term>
    <mesh_term>Melatonin</mesh_term>
    <mesh_term>Antithrombins</mesh_term>
    <mesh_term>Antithrombin III</mesh_term>
    <mesh_term>Epoetin Alfa</mesh_term>
    <mesh_term>Complement C1 Inhibitor Protein</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>July 14, 2023</submitted>
  </pending_results>
  <!-- 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/NCT02251041
org study id: CAPITL RCT
nct id: NCT02251041
lead sponsor: 
has dmc: Yes
The purpose of this study is to establish the effectiveness of the combined drug approach
      (anti-thrombin III, infliximab, apotransferrin, human recombinant erythropoietin beta,
      C1-inhibitor, glutathione, alfa-tocopherol, melatonin and epoprostenol)aimed to reduce
      ischemia-reperfusion injury during liver transplantation in eligible recipients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: log-transformed peak AST
time frame: within 72 hours following liver transplantation
description: log-transformed peak AST, where peak AST is defined as the highest value of serum AST within 72 hours following liver transplantation
measure: graft loss
time frame: 3 and 12 months after liver transplantation
description: graft loss at 3 and 12 months after liver transplantation
measure: recipient death
time frame: 3 and 12 months after liver transplantation
description: recipient death at 3 and 12 months after liver transplantation
measure: early graft dysfunction
time frame: within first 7 days
description: early graft dysfunction as defined by Olthoff
measure: Incidence of biliary strictures
time frame: within 12 months post transplantation
description: Incidence of biliary strictures within 12 months post transplantation by MRCP (magentic resonance cholangiopancreatography)
measure: IRI score
time frame: during transplantation, 1 week and 1 year after
description: IRI score during transplantation, 1 week and 1 year after liver transplantation by using the Suzuki score and Monbaliu et al.
measure: Graft rejecton
time frame: till 1 year after transplantation
description: a liver biopsy will be taken after transplantation and in cas of clinical suspicion of acute rejection
measure: Surgical complications
time frame: within 30 days after liver transplantation
description: the ranking of surgical complications will be done by using Clavien-Dindo classification
arm group label: cases
arm group type: Active Comparator
description: the group receives a combination of drugs
arm group label: controles
arm group type: Placebo Comparator
description: the group do not receive a combination of drugs, but a placebo (sodium chloride solution)
intervention type: Drug
intervention name: Antithrombin-III
arm group label: cases
intervention type: Drug
intervention name: Infliximab
arm group label: cases
intervention type: Drug
intervention name: Apotransferrin
arm group label: cases
intervention type: Drug
intervention name: Human recombinant erythropoietin
arm group label: cases
intervention type: Drug
intervention name: C1-Inhibitor
arm group label: cases
intervention type: Drug
intervention name: Glutathione
arm group label: cases
intervention type: Drug
intervention name: Alfa-tocopherol
arm group label: cases
intervention type: Drug
intervention name: Melatonin
arm group label: cases
intervention type: Drug
intervention name: Epoprostenol
arm group label: cases
intervention type: Drug
intervention name: Sodium chloride solution
arm group label: controles
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Diethard Monbaliu, MD, PhD
role: Principal Investigator
affiliation: Abdominal transplant surgery - transplant coordination, Abdominal transplant surgery lab (microbiology & immunology Dpt)
facility: 
country: Belgium
citation: Monbaliu D, Vekemans K, Hoekstra H, Vaahtera L, Libbrecht L, Derveaux K, Parkkinen J, Liu Q, Heedfeld V, Wylin T, Deckx H, Zeegers M, Balligand E, Buurman W, van Pelt J, Porte RJ, Pirenne J. Multifactorial biological modulation of warm ischemia reperfusion injury in liver transplantation from non-heart-beating donors eliminates primary nonfunction and reduces bile salt toxicity. Ann Surg. 2009 Nov;250(5):808-17. doi: 10.1097/SLA.0b013e3181bdd787.
PMID: 19826248
citation: Vekemans K, Monbaliu D, Balligand E, Heedfeld V, Jochmans I, Pirenne J, van Pelt J. Improving the function of liver grafts exposed to warm ischemia by the Leuven drug protocol: exploring the molecular basis by microarray. Liver Transpl. 2012 Feb;18(2):206-18. doi: 10.1002/lt.22446.
PMID: 21987442
responsible party type: Sponsor
mesh term: Reperfusion Injury
mesh term: Ischemia
mesh term: Wounds and Injuries
mesh term: Tocopherols
mesh term: Vitamin E
mesh term: alpha-Tocopherol
mesh term: Infliximab
mesh term: Epoprostenol
mesh term: Tezosentan
mesh term: Melatonin
mesh term: Antithrombins
mesh term: Antithrombin III
mesh term: Epoetin Alfa
mesh term: Complement C1 Inhibitor Protein
submitted: July 14, 2023