<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/NCT01680744</url>
  </required_header>
  <id_info>
    <org_study_id>R38OT22183</org_study_id>
    <nct_id>NCT01680744</nct_id>
  </id_info>
  <brief_title>The Effect of Therapeutic Hypothermia on Deceased Donor Renal Graft Outcomes - a Randomized Controlled Trial From the Region 5 Donor Management Goals Workgroup</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>California Transplant Donor Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To protect kidney function during the transplantation process by inducing mild hypothermia in&#xD;
      the deceased organ donor before organs are recovered&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The number of kidneys available for transplantation in the U.S. (~15,000/yr) does not meet&#xD;
      demand (~80,000/yr). This discrepancy will likely worsen given the increasing U.S. prevalence&#xD;
      of chronic kidney disease and is compounded by sizable organ attrition once organs have&#xD;
      entered the donation process (25-30% attrition in Region 5). Furthermore, worsening renal&#xD;
      function in donation after neurologic determination of death (DNDD) organ donors (an&#xD;
      increasingly important source of allografts) is one of the strongest predictors of delayed&#xD;
      graft function (DGF) and slow graft function (SGF) in the recipient. Both DGF and SGF are&#xD;
      associated with decreased long-term organ survival and are of major concern to the transplant&#xD;
      community.&#xD;
&#xD;
      To alleviate the aforementioned supply-demand imbalance, there are two major unmet needs that&#xD;
      must be urgently addressed. First, active medical interventions that are tested prospectively&#xD;
      to protect the organ during the donation process hold sizable potential, but remain&#xD;
      exceedingly rare. Second, compliance with pre-defined donor management protocols to restore&#xD;
      and stabilize deceased organ donor physiologic functions remains low across different&#xD;
      donation service areas, despite evidence that these protocols may improve organ yield.&#xD;
&#xD;
      The goal of this proposal, therefore, is to demonstrate that (1) therapeutic hypothermia as&#xD;
      an active medical intervention for the DNDD donor and (2) compliance with donor management&#xD;
      protocols can substantially improve allograft function and survival.&#xD;
&#xD;
      The investigators will accomplish this goal by extending an existing research infrastructure&#xD;
      (HRSA, R380T10586) across several donor service areas. As such, the investigators will bring&#xD;
      together a research network and use the power of this network to properly test a simple&#xD;
      medical intervention, therapeutic hypothermia for renal protection, in a prospective&#xD;
      randomized single blinded trial. Therapeutic hypothermia is an established cytoprotective&#xD;
      intervention that has been demonstrated to be highly protective of organs in select&#xD;
      critically ill patients. By combining two of the largest donation service areas in the nation&#xD;
      (CTDN, Northern California and OneLegacy, Southern California), the investigators will have&#xD;
      access to approximately 10% of all organ donors in the nation. This proposal aims to&#xD;
      randomize 500 DNDD organ donors, the biggest cohort enrolled in a prospective randomized&#xD;
      trial.&#xD;
&#xD;
      The investigators will further leverage this network to track trial specific donor management&#xD;
      protocols variables goals and drive tighter compliance with already established donor&#xD;
      management protocols across all donor service areas in Region 5. This will allow the&#xD;
      investigators to compile a large historical control cohort that will facilitate answering&#xD;
      additional research questions with great detail. All organ procurement areas in Region 5 have&#xD;
      confirmed their willingness to participate in this effort and contribute relevant organ donor&#xD;
      data via a shared web-portal. Through this active participation, a secondary gain will be&#xD;
      improved reporting of donor data and compliance with already accepted donor management goals.&#xD;
&#xD;
      Test of feasibility will be improvement in various kidney function metrics that are commonly&#xD;
      used to evaluate organ health during the donation process. Ultimately, the investigators&#xD;
      believe this multi-pronged approach may lead to 800 to 1000 additional kidneys that are&#xD;
      successfully transplanted nationwide each year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2012</start_date>
  <completion_date type="Actual">November 2014</completion_date>
  <primary_completion_date type="Actual">January 2014</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Renal Function</measure>
    <time_frame>12 hours of mild hypothermia</time_frame>
    <description>The primary outcome measures are renal function as determined by creatinine and cystatin c between declaration of neurological death and organ recovery in each of the two treatment groups. Delta creatinine and terminal creatinine are important predictors of graft quality and function, as demonstrated in the present data (HRSA study and Region 5 DMG/DGF study), and will be compared between the control and treatment group.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">370</enrollment>
  <condition>Deceased Organ Donor</condition>
  <condition>Mild Hypothermia</condition>
  <condition>Renal Function</condition>
  <arm_group>
    <arm_group_label>Hypothermia</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The intervention will take place after consent for donation and research has been obtained and hemodynamic stability has been achieved (mean arterial blood pressure &gt; 60 mmHg for more than one hour without an increase in vasopressors). Organ donors in the experimental group will either be actively warmed or allowed to spontaneously reach a body temperature of 34 °C.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard Treatment</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Hypothermia</intervention_name>
    <description>The intervention will take place after consent for donation and research has been obtained and hemodynamic stability has been achieved (mean arterial blood pressure &gt; 60 mmHg for more than one hour without an increase in vasopressors). Organ donors in the experimental group will either be actively warmed or allowed to spontaneously reach a body temperature of 34 °C.</description>
    <arm_group_label>Hypothermia</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  &gt; 18 years of age, deceased organ donor&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  &lt; 18 years of age, not a deceased organ donor&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of California San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2014</verification_date>
  <study_first_submitted>August 21, 2012</study_first_submitted>
  <study_first_submitted_qc>September 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 7, 2012</study_first_posted>
  <last_update_submitted>December 2, 2014</last_update_submitted>
  <last_update_submitted_qc>December 2, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 4, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Francisco</investigator_affiliation>
    <investigator_full_name>Claus Niemann</investigator_full_name>
    <investigator_title>Professor of Anesthesia &amp; Surgery</investigator_title>
  </responsible_party>
  <keyword>Transplantation</keyword>
  <keyword>Terminal creatinine</keyword>
  <keyword>Renal function</keyword>
  <keyword>GFR</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypothermia</mesh_term>
    <mesh_term>Death</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/NCT01680744
org study id: R38OT22183
nct id: NCT01680744
lead sponsor: 
collaborator: 
has dmc: Yes
To protect kidney function during the transplantation process by inducing mild hypothermia in
      the deceased organ donor before organs are recovered
The number of kidneys available for transplantation in the U.S. (~15,000/yr) does not meet
      demand (~80,000/yr). This discrepancy will likely worsen given the increasing U.S. prevalence
      of chronic kidney disease and is compounded by sizable organ attrition once organs have
      entered the donation process (25-30% attrition in Region 5). Furthermore, worsening renal
      function in donation after neurologic determination of death (DNDD) organ donors (an
      increasingly important source of allografts) is one of the strongest predictors of delayed
      graft function (DGF) and slow graft function (SGF) in the recipient. Both DGF and SGF are
      associated with decreased long-term organ survival and are of major concern to the transplant
      community.

      To alleviate the aforementioned supply-demand imbalance, there are two major unmet needs that
      must be urgently addressed. First, active medical interventions that are tested prospectively
      to protect the organ during the donation process hold sizable potential, but remain
      exceedingly rare. Second, compliance with pre-defined donor management protocols to restore
      and stabilize deceased organ donor physiologic functions remains low across different
      donation service areas, despite evidence that these protocols may improve organ yield.

      The goal of this proposal, therefore, is to demonstrate that (1) therapeutic hypothermia as
      an active medical intervention for the DNDD donor and (2) compliance with donor management
      protocols can substantially improve allograft function and survival.

      The investigators will accomplish this goal by extending an existing research infrastructure
      (HRSA, R380T10586) across several donor service areas. As such, the investigators will bring
      together a research network and use the power of this network to properly test a simple
      medical intervention, therapeutic hypothermia for renal protection, in a prospective
      randomized single blinded trial. Therapeutic hypothermia is an established cytoprotective
      intervention that has been demonstrated to be highly protective of organs in select
      critically ill patients. By combining two of the largest donation service areas in the nation
      (CTDN, Northern California and OneLegacy, Southern California), the investigators will have
      access to approximately 10% of all organ donors in the nation. This proposal aims to
      randomize 500 DNDD organ donors, the biggest cohort enrolled in a prospective randomized
      trial.

      The investigators will further leverage this network to track trial specific donor management
      protocols variables goals and drive tighter compliance with already established donor
      management protocols across all donor service areas in Region 5. This will allow the
      investigators to compile a large historical control cohort that will facilitate answering
      additional research questions with great detail. All organ procurement areas in Region 5 have
      confirmed their willingness to participate in this effort and contribute relevant organ donor
      data via a shared web-portal. Through this active participation, a secondary gain will be
      improved reporting of donor data and compliance with already accepted donor management goals.

      Test of feasibility will be improvement in various kidney function metrics that are commonly
      used to evaluate organ health during the donation process. Ultimately, the investigators
      believe this multi-pronged approach may lead to 800 to 1000 additional kidneys that are
      successfully transplanted nationwide each year.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Prevention
masking: Single (Outcomes Assessor)
measure: Renal Function
time frame: 12 hours of mild hypothermia
description: The primary outcome measures are renal function as determined by creatinine and cystatin c between declaration of neurological death and organ recovery in each of the two treatment groups. Delta creatinine and terminal creatinine are important predictors of graft quality and function, as demonstrated in the present data (HRSA study and Region 5 DMG/DGF study), and will be compared between the control and treatment group.
arm group label: Hypothermia
arm group type: Experimental
description: The intervention will take place after consent for donation and research has been obtained and hemodynamic stability has been achieved (mean arterial blood pressure > 60 mmHg for more than one hour without an increase in vasopressors). Organ donors in the experimental group will either be actively warmed or allowed to spontaneously reach a body temperature of 34 °C.
arm group label: Standard Treatment
arm group type: No Intervention
intervention type: Other
intervention name: Hypothermia
description: The intervention will take place after consent for donation and research has been obtained and hemodynamic stability has been achieved (mean arterial blood pressure > 60 mmHg for more than one hour without an increase in vasopressors). Organ donors in the experimental group will either be actively warmed or allowed to spontaneously reach a body temperature of 34 °C.
arm group label: Hypothermia
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of California, San Francisco
investigator full name: Claus Niemann
investigator title: Professor of Anesthesia & Surgery
mesh term: Hypothermia
mesh term: Death