<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/NCT04493385</url>
  </required_header>
  <id_info>
    <org_study_id>019-297</org_study_id>
    <nct_id>NCT04493385</nct_id>
  </id_info>
  <brief_title>The Hepatitis C Transplant Collaborative</brief_title>
  <official_title>Nationwide Hepatitis C NAT+ Cardiac Transplant Experience</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Baylor Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Baylor Research Institute</source>
  <oversight_info>
    <has_dmc>No</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>
      In this study we seek to test the hypothesis that safety and clinical outcomes after cardiac&#xD;
      transplantation utilizing HCV NAT+ donor organs as currently performed are acceptable.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Organ offers from donors with prior or chronic hepatitis C virus (HCV) exposure have been&#xD;
      historically underutilized for orthotopic heart transplantation because of the&#xD;
      post-transplantation risks [1, 2]. The use of HCV antibody-positive (Ab+) donors was&#xD;
      associated with attenuated survival benefit after heart transplant and increased coronary&#xD;
      allograft vasculopathy in the era before new highly effective direct-acting antiviral agents&#xD;
      (DAAs) were developed [3-5]. These DAAs target multiple steps in the HCV replication life&#xD;
      cycle [6]. Newer, well-tolerated, oral direct-acting antivirals (DAAs) have recently been&#xD;
      transforming thoracic transplant outcomes after donor-derived HCV transmission. Moreover, now&#xD;
      that HCV nucleic-acid testing (NAT), a polymerase chain reaction (PCR)-based approach to&#xD;
      detecting viral activity, is widely available and used on all US donor organs, transplant&#xD;
      centers have more relevant information about the donor, allowing better risk assessments.&#xD;
&#xD;
      As a result, the utilization of HCV NAT+ donor hearts for transplantation is rapidly gaining&#xD;
      momentum, with the obvious benefits of an enlarged donor pool [7]. Appropriately, clinical&#xD;
      safety trials are currently underway, including a multicenter effort led by the PI of this&#xD;
      proposal. Moreover, since the last ~2 years many transplant centers across the nation have&#xD;
      started transplanting HCV NAT+ donor organs as standard of care. We estimate that the number&#xD;
      of HCV+ cardiac transplants is quickly outpacing the number of trial participants. Hence, it&#xD;
      is imperative that safety assessments and risk analyses 'catch up with the real world'.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 16, 2019</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Number of donor HCV nucleic-acid testing positive (HCV NAT+) cardiac transplantation</measure>
    <time_frame>6.5 years</time_frame>
    <description>To assess the current status of donor HCV NAT+ cardiac transplantation via retrospective data collection.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Failure versus Cure Rate for HCV NAT+ Heart Transplants</measure>
    <time_frame>6.5 years</time_frame>
    <description>sustained viral response (SVR)-12 (cure-rate) for HCV negative recipient</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rate of Primary graft dysfunction (PGD)</measure>
    <time_frame>30 days</time_frame>
    <description>Rate of Expected Post-Transplant Risks</description>
  </primary_outcome>
  <primary_outcome>
    <measure>1 year mortality</measure>
    <time_frame>1 Year</time_frame>
    <description>Number of deaths</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cellular graft rejection rate</measure>
    <time_frame>6.5 years</time_frame>
    <description>Graft rejection rate</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Antibody Mediated Rejection rate</measure>
    <time_frame>6.5 years</time_frame>
    <description>Graft rejection rate</description>
  </primary_outcome>
  <enrollment type="Anticipated">500</enrollment>
  <condition>Transplant; Failure, Heart</condition>
  <condition>Hepatitis C</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Cardiac transplant recipients utilizing HCV NAT+ donor organs&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Recipient of a proven HCV NAT+ donor heart.&#xD;
&#xD;
          2. Re-transplant patients will be included.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1. Multi-organ transplantation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shelley A Hall, MD FACC</last_name>
    <role>Principal Investigator</role>
    <affiliation>BSWRI</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Joost Felius, PhD</last_name>
    <phone>214-818-8943</phone>
    <email>Joost.Felius@BSWHEALTH.ORG</email>
  </overall_contact>
  <location>
    <facility>
      <name>Baylor Scott &amp; White Health Research Institute</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joost Felius, PhD</last_name>
      <phone>214-818-8943</phone>
      <email>Joost.Felius@BSWHEALTH.ORG</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Kim EY, Ko HH, Yoshida EM. A concise review of hepatitis C in heart and lung transplantation. Can J Gastroenterol. 2011 Aug;25(8):445-8. doi: 10.1155/2011/947838.</citation>
    <PMID>21912770</PMID>
  </reference>
  <reference>
    <citation>Englum BR, Ganapathi AM, Speicher PJ, Gulack BC, Snyder LD, Davis RD, Hartwig MG. Impact of donor and recipient hepatitis C status in lung transplantation. J Heart Lung Transplant. 2016 Feb;35(2):228-35. doi: 10.1016/j.healun.2015.10.012. Epub 2015 Oct 9.</citation>
    <PMID>26615769</PMID>
  </reference>
  <reference>
    <citation>Gasink LB, Blumberg EA, Localio AR, Desai SS, Israni AK, Lautenbach E. Hepatitis C virus seropositivity in organ donors and survival in heart transplant recipients. JAMA. 2006 Oct 18;296(15):1843-50. doi: 10.1001/jama.296.15.1843.</citation>
    <PMID>17047214</PMID>
  </reference>
  <reference>
    <citation>Haji SA, Starling RC, Avery RK, Mawhorter S, Tuzcu EM, Schoenhagen P, Cook DJ, Ratliff NB, McCarthy PM, Young JB, Yamani MH. Donor hepatitis-C seropositivity is an independent risk factor for the development of accelerated coronary vasculopathy and predicts outcome after cardiac transplantation. J Heart Lung Transplant. 2004 Mar;23(3):277-83. doi: 10.1016/S1053-2498(03)00148-7.</citation>
    <PMID>15019636</PMID>
  </reference>
  <reference>
    <citation>Lee R, Kottilil S, Wilson E. Sofosbuvir/velpatasvir: a pangenotypic drug to simplify HCV therapy. Hepatol Int. 2017 Mar;11(2):161-170. doi: 10.1007/s12072-016-9776-8. Epub 2016 Dec 7.</citation>
    <PMID>27928718</PMID>
  </reference>
  <reference>
    <citation>Asselah T, Boyer N, Saadoun D, Martinot-Peignoux M, Marcellin P. Direct-acting antivirals for the treatment of hepatitis C virus infection: optimizing current IFN-free treatment and future perspectives. Liver Int. 2016 Jan;36 Suppl 1:47-57. doi: 10.1111/liv.13027.</citation>
    <PMID>26725897</PMID>
  </reference>
  <reference>
    <citation>Gottlieb RL, Hall SA. The New Direct Antiviral Agents and Hepatitis C in Thoracic Transplantation: Impact on Donors and Recipients. Curr Transplant Rep. 2018;5(2):145-152. doi: 10.1007/s40472-018-0192-y. Epub 2018 Apr 10.</citation>
    <PMID>29774177</PMID>
  </reference>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>January 25, 2023</last_update_submitted>
  <last_update_submitted_qc>January 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 26, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis C</mesh_term>
    <mesh_term>Hepatitis</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/NCT04493385
org study id: 019-297
nct id: NCT04493385
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In this study we seek to test the hypothesis that safety and clinical outcomes after cardiac
      transplantation utilizing HCV NAT+ donor organs as currently performed are acceptable.
Organ offers from donors with prior or chronic hepatitis C virus (HCV) exposure have been
      historically underutilized for orthotopic heart transplantation because of the
      post-transplantation risks [1, 2]. The use of HCV antibody-positive (Ab+) donors was
      associated with attenuated survival benefit after heart transplant and increased coronary
      allograft vasculopathy in the era before new highly effective direct-acting antiviral agents
      (DAAs) were developed [3-5]. These DAAs target multiple steps in the HCV replication life
      cycle [6]. Newer, well-tolerated, oral direct-acting antivirals (DAAs) have recently been
      transforming thoracic transplant outcomes after donor-derived HCV transmission. Moreover, now
      that HCV nucleic-acid testing (NAT), a polymerase chain reaction (PCR)-based approach to
      detecting viral activity, is widely available and used on all US donor organs, transplant
      centers have more relevant information about the donor, allowing better risk assessments.

      As a result, the utilization of HCV NAT+ donor hearts for transplantation is rapidly gaining
      momentum, with the obvious benefits of an enlarged donor pool [7]. Appropriately, clinical
      safety trials are currently underway, including a multicenter effort led by the PI of this
      proposal. Moreover, since the last ~2 years many transplant centers across the nation have
      started transplanting HCV NAT+ donor organs as standard of care. We estimate that the number
      of HCV+ cardiac transplants is quickly outpacing the number of trial participants. Hence, it
      is imperative that safety assessments and risk analyses 'catch up with the real world'.
observational model: Cohort
time perspective: Retrospective
measure: Number of donor HCV nucleic-acid testing positive (HCV NAT+) cardiac transplantation
time frame: 6.5 years
description: To assess the current status of donor HCV NAT+ cardiac transplantation via retrospective data collection.
measure: Failure versus Cure Rate for HCV NAT+ Heart Transplants
time frame: 6.5 years
description: sustained viral response (SVR)-12 (cure-rate) for HCV negative recipient
measure: Rate of Primary graft dysfunction (PGD)
time frame: 30 days
description: Rate of Expected Post-Transplant Risks
measure: 1 year mortality
time frame: 1 Year
description: Number of deaths
measure: Cellular graft rejection rate
time frame: 6.5 years
description: Graft rejection rate
measure: Antibody Mediated Rejection rate
time frame: 6.5 years
description: Graft rejection rate
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Shelley A Hall, MD FACC
role: Principal Investigator
affiliation: BSWRI
last name: Joost Felius, PhD
phone: 214-818-8943
email: Joost.Felius@BSWHEALTH.ORG
facility: 
status: Recruiting
contact: 
country: United States
citation: Kim EY, Ko HH, Yoshida EM. A concise review of hepatitis C in heart and lung transplantation. Can J Gastroenterol. 2011 Aug;25(8):445-8. doi: 10.1155/2011/947838.
PMID: 21912770
citation: Englum BR, Ganapathi AM, Speicher PJ, Gulack BC, Snyder LD, Davis RD, Hartwig MG. Impact of donor and recipient hepatitis C status in lung transplantation. J Heart Lung Transplant. 2016 Feb;35(2):228-35. doi: 10.1016/j.healun.2015.10.012. Epub 2015 Oct 9.
PMID: 26615769
citation: Gasink LB, Blumberg EA, Localio AR, Desai SS, Israni AK, Lautenbach E. Hepatitis C virus seropositivity in organ donors and survival in heart transplant recipients. JAMA. 2006 Oct 18;296(15):1843-50. doi: 10.1001/jama.296.15.1843.
PMID: 17047214
citation: Haji SA, Starling RC, Avery RK, Mawhorter S, Tuzcu EM, Schoenhagen P, Cook DJ, Ratliff NB, McCarthy PM, Young JB, Yamani MH. Donor hepatitis-C seropositivity is an independent risk factor for the development of accelerated coronary vasculopathy and predicts outcome after cardiac transplantation. J Heart Lung Transplant. 2004 Mar;23(3):277-83. doi: 10.1016/S1053-2498(03)00148-7.
PMID: 15019636
citation: Lee R, Kottilil S, Wilson E. Sofosbuvir/velpatasvir: a pangenotypic drug to simplify HCV therapy. Hepatol Int. 2017 Mar;11(2):161-170. doi: 10.1007/s12072-016-9776-8. Epub 2016 Dec 7.
PMID: 27928718
citation: Asselah T, Boyer N, Saadoun D, Martinot-Peignoux M, Marcellin P. Direct-acting antivirals for the treatment of hepatitis C virus infection: optimizing current IFN-free treatment and future perspectives. Liver Int. 2016 Jan;36 Suppl 1:47-57. doi: 10.1111/liv.13027.
PMID: 26725897
citation: Gottlieb RL, Hall SA. The New Direct Antiviral Agents and Hepatitis C in Thoracic Transplantation: Impact on Donors and Recipients. Curr Transplant Rep. 2018;5(2):145-152. doi: 10.1007/s40472-018-0192-y. Epub 2018 Apr 10.
PMID: 29774177
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Hepatitis