<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/NCT01731457</url>
  </required_header>
  <id_info>
    <org_study_id>N N403 589338-WUM-PD-Poland</org_study_id>
    <nct_id>NCT01731457</nct_id>
  </id_info>
  <brief_title>Limitation of Ischemic Injury of a Kidney Stored in Machine Perfusion in Hypothermia - Evaluation of the Impact on Kidney Allograft Function</brief_title>
  <official_title>Limitation of Ischemic Injury of a Kidney Stored in Machine Perfusion in Hypothermia - Evaluation of the Impact on Kidney Allograft Function</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Warsaw</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Warsaw</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aims of this study are:&#xD;
&#xD;
        1. assessment of ischemia injury of kidney retrieved from standard and expanded criteria&#xD;
           deceased donor before transplantation&#xD;
&#xD;
        2. assessment of efficacy of kidney ischemia injury decreasing&#xD;
&#xD;
        3. assessment of influence of kidney ischemia injury decreasing on its function after&#xD;
           transplantation For the purpose of this research one hundred kidney will be retrieved&#xD;
           from deceased donors (standard and expanded criteria deceased donors) for&#xD;
           transplantation. All kidneys before transplantation will be stored in machine perfusion&#xD;
           in hypothermia with continuous flow - Organ Recovery Systems LifePort - each single&#xD;
           kidney in self-contained perfusion system.&#xD;
&#xD;
      For the kidney allograft assessment will be used measurements performed during machine&#xD;
      perfusion in hypothermia: renal flow, resistance, lactate dehydrogenase, lactates and&#xD;
      ischemia injury markers measured in the fourth hour of perfusion in perfusion fluid.&#xD;
&#xD;
      For kidney ischemia injury assessment such markers will be measured: tumour necrosis factor&#xD;
      (TNF alfa), interleukin 2 (IL-2), interleukin 6 (IL-6), high sensitivity C-reactive protein&#xD;
      (hsCRP), platelet-derived growth factor (PDGF), cystatin C, kidney Injury Molecule (KIM-1),&#xD;
      neutrophil Gelatinase-associated Lipocalin (NGAL), complement component C3, caspase 3.&#xD;
&#xD;
      Every time from pair of retrieved kidneys each kidney will be randomise for one of the group:&#xD;
&#xD;
        -  group 1) - 50 kidneys - examined group - &quot;cured&quot; with etanercept (ENBREL) in the first&#xD;
           hour of perfusion by adding drug to perfusion fluid,&#xD;
&#xD;
        -  group 2) - 50 kidneys - control group - without intervention. Ischemia injury markers&#xD;
           will be measured in perfusion fluid by kidney two times (in the first and fourth hour of&#xD;
           perfusion) for assessment of efficacy kidney ischemia injury decreasing.&#xD;
&#xD;
      Results of measurements of kidney ischemia injury before transplantation, parameters during&#xD;
      machine perfusion in hypothermia and donor parameters will be correlated with kidney&#xD;
      allograft function post transplantation.&#xD;
&#xD;
      Immediate, delayed and slow graft function, primary non-function, kidney function assessed by&#xD;
      creatinine concentration and creatinine clearance at one day, seven days, two weeks, 1, 6 and&#xD;
      12 months post transplantation and kidney graft survival 6 and 12 months post transplantation&#xD;
      will be analysed.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>April 2011</start_date>
  <completion_date type="Actual">February 2016</completion_date>
  <primary_completion_date type="Actual">February 2014</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>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>delayed graft function</measure>
    <time_frame>one week</time_frame>
    <description>a need at least one dialysis during first week after transplantation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>12 months graft survival</measure>
    <time_frame>12 months</time_frame>
    <description>survival of kidney grafts 12 months after transplantation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>acute rejection</measure>
    <time_frame>12 months</time_frame>
    <description>biopsy proven acute rejection episodes during the first year after transplantation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>kidney ischemia injury assessment</measure>
    <time_frame>4 hours</time_frame>
    <description>ischemia injury markers measured two times (in the first and fourth hour of perfusion) in perfusion fluid: tumour necrosis factor (TNF alfa), interleukin 2 (IL-2), interleukin 6 (IL-6), high sensitivity C-reactive protein (hsCRP), platelet-derived growth factor (PDGF), cystatin C, kidney Injury Molecule (KIM-1), neutrophil Gelatinase-associated Lipocalin (NGAL), complement component C3, caspase 3</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">94</enrollment>
  <condition>Transplanted Kidney Ischemia Reperfusion Injury</condition>
  <arm_group>
    <arm_group_label>Etanercept</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>etanercept</intervention_name>
    <description>adding appropriate dose of etanercept to the perfusion fluid</description>
    <arm_group_label>Etanercept</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        DONOR STAGE&#xD;
&#xD;
          -  donor after brain death&#xD;
&#xD;
          -  seronegative HCV (hepatitis C virus)&#xD;
&#xD;
          -  procurement of two kidneys from the same donor&#xD;
&#xD;
          -  donor center distance up to 220 kilometres from Warsaw&#xD;
&#xD;
          -  availability of fluid KPS-1 and cartridge of Organ Recovery System&#xD;
&#xD;
        RECIPIENT STAGE&#xD;
&#xD;
          -  recipient of kidneys from deceased donor&#xD;
&#xD;
          -  at least eighteen recipient&#xD;
&#xD;
          -  expression of informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        DONOR STAGE&#xD;
&#xD;
          -  live kidney donor&#xD;
&#xD;
          -  seropositive HCV (hepatitis C virus)&#xD;
&#xD;
          -  get only one from the kidneys&#xD;
&#xD;
          -  &quot;doubtful&quot; donor - e.g. need for biopsy because of proteinuria or due to histological&#xD;
             lesions (e.g. tumor)&#xD;
&#xD;
          -  donor center distance above 220 kilometres from Warsaw&#xD;
&#xD;
          -  lack of fluid KPS-1 and cartridge of Organ Recovery System&#xD;
&#xD;
        RECIPIENT STAGE&#xD;
&#xD;
          -  recipient of kidney form living donor&#xD;
&#xD;
          -  minor recipient&#xD;
&#xD;
          -  no expression of informed consent&#xD;
&#xD;
          -  multiple organ recipient&#xD;
&#xD;
          -  recipient &quot;EN BLOC&quot; kidneys or two kidneys&#xD;
&#xD;
          -  recipient of kidney from donor under 14 years old&#xD;
&#xD;
          -  a need of atypical urinary diversion in kidney recipient&#xD;
&#xD;
          -  participation in another study at least in the last 30 days&#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>Piotr Domagala, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of Warsaw</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of General Surgery and Transplantation</name>
      <address>
        <city>Warsaw</city>
        <state>Mazowieckie</state>
        <zip>02-006</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>November 15, 2012</study_first_submitted>
  <study_first_submitted_qc>November 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <last_update_submitted>May 9, 2017</last_update_submitted>
  <last_update_submitted_qc>May 9, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 10, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Warsaw</investigator_affiliation>
    <investigator_full_name>Piotr Domagała</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>ischemia, reperfusion, kidney, transplantation</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>Hypothermia</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>Etanercept</mesh_term>
  </intervention_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/NCT01731457
org study id: N N403 589338-WUM-PD-Poland
nct id: NCT01731457
lead sponsor: 
has dmc: No
The aims of this study are:

        1. assessment of ischemia injury of kidney retrieved from standard and expanded criteria
           deceased donor before transplantation

        2. assessment of efficacy of kidney ischemia injury decreasing

        3. assessment of influence of kidney ischemia injury decreasing on its function after
           transplantation For the purpose of this research one hundred kidney will be retrieved
           from deceased donors (standard and expanded criteria deceased donors) for
           transplantation. All kidneys before transplantation will be stored in machine perfusion
           in hypothermia with continuous flow - Organ Recovery Systems LifePort - each single
           kidney in self-contained perfusion system.

      For the kidney allograft assessment will be used measurements performed during machine
      perfusion in hypothermia: renal flow, resistance, lactate dehydrogenase, lactates and
      ischemia injury markers measured in the fourth hour of perfusion in perfusion fluid.

      For kidney ischemia injury assessment such markers will be measured: tumour necrosis factor
      (TNF alfa), interleukin 2 (IL-2), interleukin 6 (IL-6), high sensitivity C-reactive protein
      (hsCRP), platelet-derived growth factor (PDGF), cystatin C, kidney Injury Molecule (KIM-1),
      neutrophil Gelatinase-associated Lipocalin (NGAL), complement component C3, caspase 3.

      Every time from pair of retrieved kidneys each kidney will be randomise for one of the group:

        -  group 1) - 50 kidneys - examined group - "cured" with etanercept (ENBREL) in the first
           hour of perfusion by adding drug to perfusion fluid,

        -  group 2) - 50 kidneys - control group - without intervention. Ischemia injury markers
           will be measured in perfusion fluid by kidney two times (in the first and fourth hour of
           perfusion) for assessment of efficacy kidney ischemia injury decreasing.

      Results of measurements of kidney ischemia injury before transplantation, parameters during
      machine perfusion in hypothermia and donor parameters will be correlated with kidney
      allograft function post transplantation.

      Immediate, delayed and slow graft function, primary non-function, kidney function assessed by
      creatinine concentration and creatinine clearance at one day, seven days, two weeks, 1, 6 and
      12 months post transplantation and kidney graft survival 6 and 12 months post transplantation
      will be analysed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: delayed graft function
time frame: one week
description: a need at least one dialysis during first week after transplantation
measure: 12 months graft survival
time frame: 12 months
description: survival of kidney grafts 12 months after transplantation
measure: acute rejection
time frame: 12 months
description: biopsy proven acute rejection episodes during the first year after transplantation
measure: kidney ischemia injury assessment
time frame: 4 hours
description: ischemia injury markers measured two times (in the first and fourth hour of perfusion) in perfusion fluid: tumour necrosis factor (TNF alfa), interleukin 2 (IL-2), interleukin 6 (IL-6), high sensitivity C-reactive protein (hsCRP), platelet-derived growth factor (PDGF), cystatin C, kidney Injury Molecule (KIM-1), neutrophil Gelatinase-associated Lipocalin (NGAL), complement component C3, caspase 3
arm group label: Etanercept
arm group type: Experimental
arm group label: Control
arm group type: No Intervention
intervention type: Drug
intervention name: etanercept
description: adding appropriate dose of etanercept to the perfusion fluid
arm group label: Etanercept
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Piotr Domagala, MD, PhD
role: Principal Investigator
affiliation: Medical University of Warsaw
facility: 
country: Poland
responsible party type: Principal Investigator
investigator affiliation: Medical University of Warsaw
investigator full name: Piotr Domagała
investigator title: MD, PhD
mesh term: Reperfusion Injury
mesh term: Ischemia
mesh term: Hypothermia
mesh term: Wounds and Injuries
mesh term: Etanercept