<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/NCT03837522</url>
  </required_header>
  <id_info>
    <org_study_id>29880</org_study_id>
    <nct_id>NCT03837522</nct_id>
  </id_info>
  <brief_title>Trial to Define the Benefits and Harms of Deceased Donor Kidney Procurement Biopsies</brief_title>
  <official_title>Pilot Randomized Trial to Define the Benefits and Harms of Deceased Donor Kidney Procurement Biopsies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Louis University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Mid-America Transplant</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>St. Louis University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to compare the impact of the availability of biopsy&#xD;
      results at the time of organ offers on the use and outcomes of kidneys from deceased donors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Randomization of biopsy processing will be performed at the level of the deceased donor.&#xD;
&#xD;
      If the participant agrees to be in this study and signs the informed consent, at the time&#xD;
      that a kidney is accepted for them, the accepted deceased donor will be randomized, like a&#xD;
      flip of a coin, to one of two groups.&#xD;
&#xD;
        -  Group 1: biopsies will be processed immediately (routine &quot;frozen section&quot;) and results&#xD;
           will be available to clinical teams at the time of the organ offers. Frozen section&#xD;
           refers to a process where tissue from the biopsy sample is prepared by freezing and then&#xD;
           slicing the tissue sample. Importantly, it can be done in about 15 to 20 minutes. Frozen&#xD;
           sections are done when an immediate answer is needed; however, the quality of the sample&#xD;
           is not always optimal.&#xD;
&#xD;
        -  Group 2: biopsies will be processed using &quot;permanent sections&quot; - these results will not&#xD;
           be available until after the organ is transplanted. Permanent section refers to a&#xD;
           process where tissue from the biopsy sample is prepared by placing the tissue sample in&#xD;
           a fixative, called formalin, to preserve the tissue, processing it through other&#xD;
           additional solutions, and then placing it in paraffin wax. After the wax hardens, the&#xD;
           tissue is cut into very thin slices, which are placed on slides and stained. This&#xD;
           process normally takes several days.&#xD;
&#xD;
      There is a 50/50 chance that the donor will be randomized to immediate biopsy processing by&#xD;
      frozen section, versus permanent processing that yields results after transplant. If for any&#xD;
      reason their surgeon feels that it would not be safe to proceed without the biopsy result, he&#xD;
      or she will have the ability to receive the results of the biopsy before the transplant. The&#xD;
      study team will record any episodes of this occurrence.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 17, 2019</start_date>
  <completion_date type="Actual">February 4, 2023</completion_date>
  <primary_completion_date type="Actual">June 30, 2022</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>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>risk-adjusted kidney yield</measure>
    <time_frame>3 years</time_frame>
    <description>per kidney donor with an immediate vs delayed procurement biopsy processing (this will serve as the primary organ utilization metric, and is the adjusted converse of organ discard)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Life years for transplant recipients</measure>
    <time_frame>3 years</time_frame>
    <description>Life years or survival for candidates after offer of kidney with an immediate vs delayed procurement biopsy processing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with delayed graft function</measure>
    <time_frame>3 years</time_frame>
    <description>Number of participants with delayed graft function after transplant of kidney with an immediate vs delayed procurement biopsy processing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with graft survival</measure>
    <time_frame>3 years</time_frame>
    <description>Number of participants with graft survival after transplant of kidney with an immediate vs delayed procurement biopsy processing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cold ischemia time</measure>
    <time_frame>3 years</time_frame>
    <description>Cold ischemia time for kidneys transplanted after immediate vs delayed procurement biopsy processing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient survival after transplant</measure>
    <time_frame>3 years</time_frame>
    <description>Patient survival after transplant of kidney with an immediate vs delayed procurement biopsy processing</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Kidney Transplant</condition>
  <condition>Renal Transplant</condition>
  <arm_group>
    <arm_group_label>Procurement Biopsy: Frozen section</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In the routine care condition, biopsies will be processed immediately as a frozen section.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Procurement Biopsy: Permanent section</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In the intervention group, the biopsy processing will be delayed to permanent section, and therefore not available until allocation is complete.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Procurement Biopsy: Frozen section</intervention_name>
    <description>Frozen sections are prepared by freezing and slicing the tissue sample; importantly, they can be done in about 15 to 20 minutes. Frozen sections are done when an immediate answer is needed, but do not provide optimal quality.</description>
    <arm_group_label>Procurement Biopsy: Frozen section</arm_group_label>
    <other_name>Immediate results</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Procurement Biopsy: Permanent section</intervention_name>
    <description>Permanent sections are prepared by placing the tissue in fixative (usually formalin) to preserve the tissue, processing it through additional solutions, and then placing it in paraffin wax. After the wax has hardened, the tissue is cut into very thin slices, which are placed on slides and stained. The process normally takes several days.</description>
    <arm_group_label>Procurement Biopsy: Permanent section</arm_group_label>
    <other_name>Delayed results</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Kidney transplant candidate&#xD;
&#xD;
          -  On waitlist for kidney transplant at the time of informed consent at one of the&#xD;
             participating sites&#xD;
&#xD;
          -  Age 18 or older&#xD;
&#xD;
          -  Willing and able to provide informed consent for participation in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable or unwilling to provide informed consent to participate in the study&#xD;
&#xD;
          -  Younger than 18 years old&#xD;
&#xD;
          -  Not on waitlist for kidney transplant at the time of informed consent at one of the&#xD;
             participating centers&#xD;
&#xD;
          -  Candidates for or recipients of multi-organ transplants (kidney along with another&#xD;
             solid organ)&#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>Krista Lentine, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. Louis University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Saint Louis University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.kidney.org/newsletter/board-to-board/progress-discarding-kidney-can-discard-life</url>
    <description>National Kidney Foundation. Progress: Discarding a kidney can discard a life. Overview of Consensus Conference to Decrease Kidney Discards.</description>
  </link>
  <link>
    <url>http://statistics.eurotransplant.org</url>
    <description>Eurotransplant Statistics Report Library.</description>
  </link>
  <reference>
    <citation>Cooper M, Formica R, Friedewald J, Hirose R, O'Connor K, Mohan S, Schold J, Axelrod D, Pastan S. Report of National Kidney Foundation Consensus Conference to Decrease Kidney Discards. Clin Transplant. 2019 Jan;33(1):e13419. doi: 10.1111/ctr.13419. Epub 2018 Oct 21.</citation>
    <PMID>30345720</PMID>
  </reference>
  <reference>
    <citation>Wang CJ, Wetmore JB, Crary GS, Kasiske BL. The Donor Kidney Biopsy and Its Implications in Predicting Graft Outcomes: A Systematic Review. Am J Transplant. 2015 Jul;15(7):1903-14. doi: 10.1111/ajt.13213. Epub 2015 Mar 13.</citation>
    <PMID>25772854</PMID>
  </reference>
  <reference>
    <citation>Naesens M. Zero-Time Renal Transplant Biopsies: A Comprehensive Review. Transplantation. 2016 Jul;100(7):1425-39. doi: 10.1097/TP.0000000000001018.</citation>
    <PMID>26599490</PMID>
  </reference>
  <reference>
    <citation>Hart A, Smith JM, Skeans MA, Gustafson SK, Stewart DE, Cherikh WS, Wainright JL, Kucheryavaya A, Woodbury M, Snyder JJ, Kasiske BL, Israni AK. OPTN/SRTR 2015 Annual Data Report: Kidney. Am J Transplant. 2017 Jan;17 Suppl 1(Suppl 1):21-116. doi: 10.1111/ajt.14124.</citation>
    <PMID>28052609</PMID>
  </reference>
  <reference>
    <citation>De Vusser K, Lerut E, Kuypers D, Vanrenterghem Y, Jochmans I, Monbaliu D, Pirenne J, Naesens M. The predictive value of kidney allograft baseline biopsies for long-term graft survival. J Am Soc Nephrol. 2013 Nov;24(11):1913-23. doi: 10.1681/ASN.2012111081. Epub 2013 Aug 15.</citation>
    <PMID>23949799</PMID>
  </reference>
  <reference>
    <citation>Kasiske BL, Stewart DE, Bista BR, Salkowski N, Snyder JJ, Israni AK, Crary GS, Rosendale JD, Matas AJ, Delmonico FL. The role of procurement biopsies in acceptance decisions for kidneys retrieved for transplant. Clin J Am Soc Nephrol. 2014 Mar;9(3):562-71. doi: 10.2215/CJN.07610713. Epub 2014 Feb 20.</citation>
    <PMID>24558053</PMID>
  </reference>
  <reference>
    <citation>Husain SA, Chiles MC, Lee S, Pastan SO, Patzer RE, Tanriover B, Ratner LE, Mohan S. Characteristics and Performance of Unilateral Kidney Transplants from Deceased Donors. Clin J Am Soc Nephrol. 2018 Jan 6;13(1):118-127. doi: 10.2215/CJN.06550617. Epub 2017 Dec 7.</citation>
    <PMID>29217537</PMID>
  </reference>
  <reference>
    <citation>Hart A, Smith JM, Skeans MA, Gustafson SK, Wilk AR, Robinson A, Wainright JL, Haynes CR, Snyder JJ, Kasiske BL, Israni AK. OPTN/SRTR 2016 Annual Data Report: Kidney. Am J Transplant. 2018 Jan;18 Suppl 1(Suppl 1):18-113. doi: 10.1111/ajt.14557.</citation>
    <PMID>29292608</PMID>
  </reference>
  <reference>
    <citation>Walker PD, Cavallo T, Bonsib SM; Ad Hoc Committee on Renal Biopsy Guidelines of the Renal Pathology Society. Practice guidelines for the renal biopsy. Mod Pathol. 2004 Dec;17(12):1555-63. doi: 10.1038/modpathol.3800239.</citation>
    <PMID>15272280</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>February 8, 2019</study_first_submitted>
  <study_first_submitted_qc>February 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>March 28, 2023</last_update_submitted>
  <last_update_submitted_qc>March 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>St. Louis University</investigator_affiliation>
    <investigator_full_name>Krista Lentine MD, PhD</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Biopsy</keyword>
  <keyword>Deceased kidney donation</keyword>
  <keyword>Kidney transplantation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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/NCT03837522
org study id: 29880
nct id: NCT03837522
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this research study is to compare the impact of the availability of biopsy
      results at the time of organ offers on the use and outcomes of kidneys from deceased donors.
Randomization of biopsy processing will be performed at the level of the deceased donor.

      If the participant agrees to be in this study and signs the informed consent, at the time
      that a kidney is accepted for them, the accepted deceased donor will be randomized, like a
      flip of a coin, to one of two groups.

        -  Group 1: biopsies will be processed immediately (routine "frozen section") and results
           will be available to clinical teams at the time of the organ offers. Frozen section
           refers to a process where tissue from the biopsy sample is prepared by freezing and then
           slicing the tissue sample. Importantly, it can be done in about 15 to 20 minutes. Frozen
           sections are done when an immediate answer is needed; however, the quality of the sample
           is not always optimal.

        -  Group 2: biopsies will be processed using "permanent sections" - these results will not
           be available until after the organ is transplanted. Permanent section refers to a
           process where tissue from the biopsy sample is prepared by placing the tissue sample in
           a fixative, called formalin, to preserve the tissue, processing it through other
           additional solutions, and then placing it in paraffin wax. After the wax hardens, the
           tissue is cut into very thin slices, which are placed on slides and stained. This
           process normally takes several days.

      There is a 50/50 chance that the donor will be randomized to immediate biopsy processing by
      frozen section, versus permanent processing that yields results after transplant. If for any
      reason their surgeon feels that it would not be safe to proceed without the biopsy result, he
      or she will have the ability to receive the results of the biopsy before the transplant. The
      study team will record any episodes of this occurrence.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: risk-adjusted kidney yield
time frame: 3 years
description: per kidney donor with an immediate vs delayed procurement biopsy processing (this will serve as the primary organ utilization metric, and is the adjusted converse of organ discard)
measure: Life years for transplant recipients
time frame: 3 years
description: Life years or survival for candidates after offer of kidney with an immediate vs delayed procurement biopsy processing
measure: Number of participants with delayed graft function
time frame: 3 years
description: Number of participants with delayed graft function after transplant of kidney with an immediate vs delayed procurement biopsy processing
measure: Number of participants with graft survival
time frame: 3 years
description: Number of participants with graft survival after transplant of kidney with an immediate vs delayed procurement biopsy processing
measure: Cold ischemia time
time frame: 3 years
description: Cold ischemia time for kidneys transplanted after immediate vs delayed procurement biopsy processing
measure: Patient survival after transplant
time frame: 3 years
description: Patient survival after transplant of kidney with an immediate vs delayed procurement biopsy processing
arm group label: Procurement Biopsy: Frozen section
arm group type: Active Comparator
description: In the routine care condition, biopsies will be processed immediately as a frozen section.
arm group label: Procurement Biopsy: Permanent section
arm group type: Active Comparator
description: In the intervention group, the biopsy processing will be delayed to permanent section, and therefore not available until allocation is complete.
intervention type: Diagnostic Test
intervention name: Procurement Biopsy: Frozen section
description: Frozen sections are prepared by freezing and slicing the tissue sample; importantly, they can be done in about 15 to 20 minutes. Frozen sections are done when an immediate answer is needed, but do not provide optimal quality.
arm group label: Procurement Biopsy: Frozen section
other name: Immediate results
intervention type: Diagnostic Test
intervention name: Procurement Biopsy: Permanent section
description: Permanent sections are prepared by placing the tissue in fixative (usually formalin) to preserve the tissue, processing it through additional solutions, and then placing it in paraffin wax. After the wax has hardened, the tissue is cut into very thin slices, which are placed on slides and stained. The process normally takes several days.
arm group label: Procurement Biopsy: Permanent section
other name: Delayed results
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Krista Lentine, MD, PhD
role: Principal Investigator
affiliation: St. Louis University
facility: 
facility: 
country: United States
url: https://www.kidney.org/newsletter/board-to-board/progress-discarding-kidney-can-discard-life
description: National Kidney Foundation. Progress: Discarding a kidney can discard a life. Overview of Consensus Conference to Decrease Kidney Discards.
url: http://statistics.eurotransplant.org
description: Eurotransplant Statistics Report Library.
citation: Cooper M, Formica R, Friedewald J, Hirose R, O'Connor K, Mohan S, Schold J, Axelrod D, Pastan S. Report of National Kidney Foundation Consensus Conference to Decrease Kidney Discards. Clin Transplant. 2019 Jan;33(1):e13419. doi: 10.1111/ctr.13419. Epub 2018 Oct 21.
PMID: 30345720
citation: Wang CJ, Wetmore JB, Crary GS, Kasiske BL. The Donor Kidney Biopsy and Its Implications in Predicting Graft Outcomes: A Systematic Review. Am J Transplant. 2015 Jul;15(7):1903-14. doi: 10.1111/ajt.13213. Epub 2015 Mar 13.
PMID: 25772854
citation: Naesens M. Zero-Time Renal Transplant Biopsies: A Comprehensive Review. Transplantation. 2016 Jul;100(7):1425-39. doi: 10.1097/TP.0000000000001018.
PMID: 26599490
citation: Hart A, Smith JM, Skeans MA, Gustafson SK, Stewart DE, Cherikh WS, Wainright JL, Kucheryavaya A, Woodbury M, Snyder JJ, Kasiske BL, Israni AK. OPTN/SRTR 2015 Annual Data Report: Kidney. Am J Transplant. 2017 Jan;17 Suppl 1(Suppl 1):21-116. doi: 10.1111/ajt.14124.
PMID: 28052609
citation: De Vusser K, Lerut E, Kuypers D, Vanrenterghem Y, Jochmans I, Monbaliu D, Pirenne J, Naesens M. The predictive value of kidney allograft baseline biopsies for long-term graft survival. J Am Soc Nephrol. 2013 Nov;24(11):1913-23. doi: 10.1681/ASN.2012111081. Epub 2013 Aug 15.
PMID: 23949799
citation: Kasiske BL, Stewart DE, Bista BR, Salkowski N, Snyder JJ, Israni AK, Crary GS, Rosendale JD, Matas AJ, Delmonico FL. The role of procurement biopsies in acceptance decisions for kidneys retrieved for transplant. Clin J Am Soc Nephrol. 2014 Mar;9(3):562-71. doi: 10.2215/CJN.07610713. Epub 2014 Feb 20.
PMID: 24558053
citation: Husain SA, Chiles MC, Lee S, Pastan SO, Patzer RE, Tanriover B, Ratner LE, Mohan S. Characteristics and Performance of Unilateral Kidney Transplants from Deceased Donors. Clin J Am Soc Nephrol. 2018 Jan 6;13(1):118-127. doi: 10.2215/CJN.06550617. Epub 2017 Dec 7.
PMID: 29217537
citation: Hart A, Smith JM, Skeans MA, Gustafson SK, Wilk AR, Robinson A, Wainright JL, Haynes CR, Snyder JJ, Kasiske BL, Israni AK. OPTN/SRTR 2016 Annual Data Report: Kidney. Am J Transplant. 2018 Jan;18 Suppl 1(Suppl 1):18-113. doi: 10.1111/ajt.14557.
PMID: 29292608
citation: Walker PD, Cavallo T, Bonsib SM; Ad Hoc Committee on Renal Biopsy Guidelines of the Renal Pathology Society. Practice guidelines for the renal biopsy. Mod Pathol. 2004 Dec;17(12):1555-63. doi: 10.1038/modpathol.3800239.
PMID: 15272280
responsible party type: Principal Investigator
investigator affiliation: St. Louis University
investigator full name: Krista Lentine MD, PhD
investigator title: Professor
mesh term: Death