<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/NCT04415658</url>
  </required_header>
  <id_info>
    <org_study_id>ODRC-002</org_study_id>
    <nct_id>NCT04415658</nct_id>
  </id_info>
  <brief_title>Intravenous Thyroxine for Heart-Eligible Organ Donors</brief_title>
  <official_title>A Multicenter Randomized Placebo-Controlled Trial of Intravenous Thyroxine for Heart-Eligible Brain Dead Organ Donors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Mid-America Transplant</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized controlled trial will evaluate whether intravenous thyroxine infusion given&#xD;
      to brain-dead organ donors who are eligible to donate hearts for 12 hours will result in more&#xD;
      hearts transplanted than saline placebo&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Brain death frequently induces hemodynamic instability and cardiac stunning.&#xD;
      Impairments in cardiac performance are major contributors to hearts from otherwise eligible&#xD;
      organ donors not being transplanted. Deficiencies in pituitary hormones (including thyroid&#xD;
      stimulating hormone) may contribute to hemodynamic instability and replacement of thyroid&#xD;
      hormone has been proposed as a means of improving stability and increasing hearts available&#xD;
      for transplantation. Intravenous thyroxine is commonly used in donor management. However,&#xD;
      small controlled trials have not been able to demonstrate efficacy.&#xD;
&#xD;
      Methods: This multicenter study will involve organ procurement organizations (OPOs) across&#xD;
      the country. A total of 800 heart-eligible brain dead organ donors who require vasopressor&#xD;
      support will be randomly assigned to intravenous thyroxine for at least 12-hours or saline&#xD;
      placebo. The primary study hypothesis is that thyroxine treatment results in more hearts&#xD;
      transplanted. Additional outcome measures are time to achieve hemodynamic stability (weaning&#xD;
      off vasopressors) and improvement in cardiac ejection fraction on echocardiography.&#xD;
&#xD;
      Discussion: This will be the largest randomized controlled study to evaluate the efficacy of&#xD;
      thyroid hormone treatment for organ donor management. By collaborating across multiple OPOs,&#xD;
      it will be able to enroll an adequate number of donors and be powered to definitively answer&#xD;
      the critical question of whether treatment increases hearts transplanted and/or provides&#xD;
      other hemodynamic benefits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 1, 2020</start_date>
  <completion_date type="Actual">December 6, 2022</completion_date>
  <primary_completion_date type="Actual">November 6, 2022</primary_completion_date>
  <phase>Phase 3</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Heart transplanted</measure>
    <time_frame>One week</time_frame>
    <description>Whether heart is transplanted into living recipient</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Graft function</measure>
    <time_frame>30 days</time_frame>
    <description>30-day graft survival of hearts transplanted from study donors</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time till off vasopressors</measure>
    <time_frame>72 hours</time_frame>
    <description>Time in hours from randomization to when weaned off vasopressors (except vasopressin)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weaned off vasopressors</measure>
    <time_frame>12 hours</time_frame>
    <description>Weaned off vasopressors within twelve hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to order echo</measure>
    <time_frame>72 hours</time_frame>
    <description>Time till hemodynamic stability permits ordering initial echocardiogram</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ejection fraction</measure>
    <time_frame>72 hours</time_frame>
    <description>Left ventricular ejection fraction measured on first echocardiography</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Total organs transplanted</measure>
    <time_frame>One week</time_frame>
    <description>Total number of organs transplanted</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">840</enrollment>
  <condition>Brain Death</condition>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>Thyroxine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous thyroxine infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Saline Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intravenous saline infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Thyroxine</intervention_name>
    <description>Infusion prepared by mixing 500 μg of drug in 500-ml of normal saline (i.e. concentration of 1 μg/ml) and enclosing the bag in an opaque sleeve. Infusion started at 30 μg/hour (30 ml/hour) for twelve hours.</description>
    <arm_group_label>Thyroxine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>The placebo will be a 500-ml bag of normal saline (without active drug) also enclosed in an opaque sleeve. This infusion will also be started at 30 ml/hour for twelve hours.</description>
    <arm_group_label>Saline Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Declared dead by neurologic criteria (brain dead)&#xD;
&#xD;
          -  Authorization for organ donation and research&#xD;
&#xD;
          -  On one or more vasopressors and/or inotropes&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Brain death declared more than 24 hours prior&#xD;
&#xD;
          -  Only vasopressor is vasopressin&#xD;
&#xD;
          -  Weight &lt; 45 kg (100 lbs)&#xD;
&#xD;
          -  Known coronary artery disease or history of myocardial infarction&#xD;
&#xD;
          -  Known valvular heart disease&#xD;
&#xD;
          -  Prior sternotomy or cardiac surgery&#xD;
&#xD;
          -  Donor at VA hospital&#xD;
&#xD;
          -  Received intravenous or oral thyroxine within past month&#xD;
&#xD;
          -  Known HIV+ status&#xD;
&#xD;
          -  Other reason donor is unable to receive study drug (determined by on-site personnel)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>14 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rajat Dhar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Donor Network of Arizona</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85013</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lifesharing</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Donor Alliance</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OurLegacy</name>
      <address>
        <city>Maitland</city>
        <state>Florida</state>
        <zip>32751</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Iowa Donor Network</name>
      <address>
        <city>North Liberty</city>
        <state>Iowa</state>
        <zip>52317</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Midwest Transplant Network</name>
      <address>
        <city>Westwood</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Louisiana Organ Procurement Agency</name>
      <address>
        <city>Covington</city>
        <state>Louisiana</state>
        <zip>70433</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mid-America Transplant Services</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lifebanc</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LifeShare of Oklahoma</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southwest Transplant Alliance</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Organ Sharing Alliance</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DonorConnect</name>
      <address>
        <city>Murray</city>
        <state>Utah</state>
        <zip>84107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LifeCenter Northwest</name>
      <address>
        <city>Bellevue</city>
        <state>Washington</state>
        <zip>98006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Dhar R, Stahlschmidt E, Yan Y, Marklin G. A randomized trial comparing triiodothyronine (T3) with thyroxine (T4) for hemodynamically unstable brain-dead organ donors. Clin Transplant. 2019 Mar;33(3):e13486. doi: 10.1111/ctr.13486. Epub 2019 Feb 12.</citation>
    <PMID>30689222</PMID>
  </reference>
  <reference>
    <citation>Dhar R, Stahlschmidt E, Marklin G. A Randomized Trial of Intravenous Thyroxine for Brain-Dead Organ Donors With Impaired Cardiac Function. Prog Transplant. 2020 Mar;30(1):48-55. doi: 10.1177/1526924819893295. Epub 2019 Dec 5.</citation>
    <PMID>31802716</PMID>
  </reference>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>December 8, 2022</last_update_submitted>
  <last_update_submitted_qc>December 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Washington University School of Medicine</investigator_affiliation>
    <investigator_full_name>Rajat Dhar</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Organ donor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Death</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol: Appendix (Data Forms)</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 1, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/58/NCT04415658/Prot_003.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan: Study Protocol and SAP</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 1, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/58/NCT04415658/Prot_SAP_005.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04415658
org study id: ODRC-002
nct id: NCT04415658
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This randomized controlled trial will evaluate whether intravenous thyroxine infusion given
      to brain-dead organ donors who are eligible to donate hearts for 12 hours will result in more
      hearts transplanted than saline placebo
Background: Brain death frequently induces hemodynamic instability and cardiac stunning.
      Impairments in cardiac performance are major contributors to hearts from otherwise eligible
      organ donors not being transplanted. Deficiencies in pituitary hormones (including thyroid
      stimulating hormone) may contribute to hemodynamic instability and replacement of thyroid
      hormone has been proposed as a means of improving stability and increasing hearts available
      for transplantation. Intravenous thyroxine is commonly used in donor management. However,
      small controlled trials have not been able to demonstrate efficacy.

      Methods: This multicenter study will involve organ procurement organizations (OPOs) across
      the country. A total of 800 heart-eligible brain dead organ donors who require vasopressor
      support will be randomly assigned to intravenous thyroxine for at least 12-hours or saline
      placebo. The primary study hypothesis is that thyroxine treatment results in more hearts
      transplanted. Additional outcome measures are time to achieve hemodynamic stability (weaning
      off vasopressors) and improvement in cardiac ejection fraction on echocardiography.

      Discussion: This will be the largest randomized controlled study to evaluate the efficacy of
      thyroid hormone treatment for organ donor management. By collaborating across multiple OPOs,
      it will be able to enroll an adequate number of donors and be powered to definitively answer
      the critical question of whether treatment increases hearts transplanted and/or provides
      other hemodynamic benefits.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Heart transplanted
time frame: One week
description: Whether heart is transplanted into living recipient
measure: Graft function
time frame: 30 days
description: 30-day graft survival of hearts transplanted from study donors
measure: Time till off vasopressors
time frame: 72 hours
description: Time in hours from randomization to when weaned off vasopressors (except vasopressin)
measure: Weaned off vasopressors
time frame: 12 hours
description: Weaned off vasopressors within twelve hours
measure: Time to order echo
time frame: 72 hours
description: Time till hemodynamic stability permits ordering initial echocardiogram
measure: Ejection fraction
time frame: 72 hours
description: Left ventricular ejection fraction measured on first echocardiography
measure: Total organs transplanted
time frame: One week
description: Total number of organs transplanted
arm group label: Thyroxine
arm group type: Experimental
description: Intravenous thyroxine infusion
arm group label: Saline Placebo
arm group type: Placebo Comparator
description: Intravenous saline infusion
intervention type: Drug
intervention name: Thyroxine
description: Infusion prepared by mixing 500 μg of drug in 500-ml of normal saline (i.e. concentration of 1 μg/ml) and enclosing the bag in an opaque sleeve. Infusion started at 30 μg/hour (30 ml/hour) for twelve hours.
arm group label: Thyroxine
intervention type: Drug
intervention name: Saline
description: The placebo will be a 500-ml bag of normal saline (without active drug) also enclosed in an opaque sleeve. This infusion will also be started at 30 ml/hour for twelve hours.
arm group label: Saline Placebo
criteria: 
gender: All
minimum age: 14 Years
maximum age: 55 Years
healthy volunteers: No
last name: Rajat Dhar, MD
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
facility: 
facility: 
facility: 
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facility: 
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facility: 
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facility: 
facility: 
country: United States
citation: Dhar R, Stahlschmidt E, Yan Y, Marklin G. A randomized trial comparing triiodothyronine (T3) with thyroxine (T4) for hemodynamically unstable brain-dead organ donors. Clin Transplant. 2019 Mar;33(3):e13486. doi: 10.1111/ctr.13486. Epub 2019 Feb 12.
PMID: 30689222
citation: Dhar R, Stahlschmidt E, Marklin G. A Randomized Trial of Intravenous Thyroxine for Brain-Dead Organ Donors With Impaired Cardiac Function. Prog Transplant. 2020 Mar;30(1):48-55. doi: 10.1177/1526924819893295. Epub 2019 Dec 5.
PMID: 31802716
responsible party type: Principal Investigator
investigator affiliation: Washington University School of Medicine
investigator full name: Rajat Dhar
investigator title: Associate Professor
mesh term: Brain Death
provided document: 
provided document: 