<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/NCT03801707</url>
  </required_header>
  <id_info>
    <org_study_id>2018H0499</org_study_id>
    <nct_id>NCT03801707</nct_id>
  </id_info>
  <brief_title>Utilization of Hepatitis C Positive Kidneys in Negative Recipients</brief_title>
  <official_title>An Open Label, Proof of Concept Study to Evaluate the Feasibility and Safety of Kidney Transplant From HCV Positive Donors Into HCV Negative Recipient</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ohio State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ohio State University</source>
  <oversight_info>
    <has_dmc>No</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>
      To evaluate the safety and feasibility of transplanting kidneys from Hepatitis C virus (HCV)&#xD;
      infected donors into recipients without HCV infection&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be an open label, prospective, interventional, proof of concept study to evaluate&#xD;
      the feasibility and safety of kidney transplant from HCV positive donors into HCV negative&#xD;
      recipients using treatment with pan-genotypic direct acting antiviral therapies (DAAS) for&#xD;
      treatment of post-transplant HCV transmission&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 22, 2019</start_date>
  <completion_date type="Actual">April 30, 2021</completion_date>
  <primary_completion_date type="Actual">April 28, 2021</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of Patients With Undetectable Hepatitis C Virus (HCV) Polymerase Chain Reaction (PCR) at 12 Weeks After Completion of HCV Treatment</measure>
    <time_frame>12 weeks</time_frame>
    <description>Proportion of patients with undetectable hepatitis C virus (HCV) polymerase chain reaction (PCR) at 12 weeks after completion of HCV treatment was to test the efficacy of the treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Elevation in Liver Enzyme &gt;5 Times the Upper Limits, Development of Acute Cholestatic Hepatitis , or Intolerance to Direct Acting Antiviral Therapies</measure>
    <time_frame>12 weeks</time_frame>
    <description>Elevation in liver enzyme &gt;5 times the upper limits, development of acute cholestatic hepatitis , or intolerance to Direct acting antiviral therapies was to test the safety of utilizing HepC positive kidneys for transplant.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Estimated Glomerular Filtration Rate (eGFR) at 6 and 12 Months Post-transplant</measure>
    <time_frame>6 and 12 months</time_frame>
    <description>Estimated glomerular filtration rate (eGFR) at 6 and 12 months post-transplant was to test the safety of utilizing of HepC positive kidneys.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient's Survival at 6 and 12 Months</measure>
    <time_frame>6 and 12 months</time_frame>
    <description>Patient's survival at 6 and 12 months measuring safety of utilizing of HepC positive kidneys.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Graft Survival at 6 and 12 Months</measure>
    <time_frame>12 months</time_frame>
    <description>Graft survival at 6 and 12 months measuring safety of utilizing HepC positive kidneys.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Kidney Transplant</condition>
  <condition>Hepatitis C</condition>
  <condition>HCV</condition>
  <arm_group>
    <arm_group_label>Intervention group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>kidney transplant recipients who receive kidney allograft from hepatitis C viremic donors followed by treatment with direct acting antiviral therapies.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sofosbuvir / Velpatasvir Oral Tablet [Epclusa]</intervention_name>
    <description>fixed dose combination medication once a day for 12 weeks for the treatment of hepatitis C</description>
    <arm_group_label>Intervention group</arm_group_label>
    <other_name>Epclusa</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glecaprevir/Pibrentasvir 100 MG-40 MG Oral Tablet [MAVYRET]</intervention_name>
    <description>Three tablets once a day for 12 weeks for treatment of hepatitis C</description>
    <arm_group_label>Intervention group</arm_group_label>
    <other_name>Mavyret</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Recipient Inclusion/Exclusion Criteria:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult age &gt;18 years able to provide consent&#xD;
&#xD;
          -  Lack of available living donor&#xD;
&#xD;
          -  Calculated pre-transplant reactive panel (cPRA) of &lt;80%&#xD;
&#xD;
          -  Estimated post-transplant survival (EPTS) index &gt;20% and &lt;80%&#xD;
&#xD;
          -  Negative pre-transplant human immunodeficiency virus (HIV), hepatitis C virus (HCV),&#xD;
             and hepatitis B virus (HBV) serology and blood HCV polymerase chain reaction (PCR)&#xD;
&#xD;
          -  No clinically significant pre-transplant liver disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Living donor available&#xD;
&#xD;
          -  Dialysis time &gt;5 years&#xD;
&#xD;
          -  Listing for multi-organ transplantation&#xD;
&#xD;
          -  Active or recent history (&lt;6 months) of alcohol abuse or substance abuse&#xD;
&#xD;
          -  Clinically significant liver disease as determined by principal investigator&#xD;
&#xD;
          -  History of hepatocarcinoma&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Refusal to accept blood transfusion&#xD;
&#xD;
          -  HIV infection&#xD;
&#xD;
          -  HCV pcr or antibody positive&#xD;
&#xD;
          -  HBV infection&#xD;
&#xD;
        Donor Inclusion Criteria:&#xD;
&#xD;
          -  Positive HCV PCR at time of donation&#xD;
&#xD;
          -  Kidney donor profile index (KDPI)&lt;85%&#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>Reem Daloul, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ohio State University School of Biomedical Science: The Ohio State University College of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brenda Cuson</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.usrds.org/annual-data-report/current-adr/</url>
    <description>USRDS Annual Data Report 2017</description>
  </link>
  <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>Curry MP, O'Leary JG, Bzowej N, Muir AJ, Korenblat KM, Fenkel JM, Reddy KR, Lawitz E, Flamm SL, Schiano T, Teperman L, Fontana R, Schiff E, Fried M, Doehle B, An D, McNally J, Osinusi A, Brainard DM, McHutchison JG, Brown RS Jr, Charlton M; ASTRAL-4 Investigators. Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis. N Engl J Med. 2015 Dec 31;373(27):2618-28. doi: 10.1056/NEJMoa1512614. Epub 2015 Nov 16.</citation>
    <PMID>26569658</PMID>
  </reference>
  <reference>
    <citation>Feld JJ, Jacobson IM, Hezode C, Asselah T, Ruane PJ, Gruener N, Abergel A, Mangia A, Lai CL, Chan HL, Mazzotta F, Moreno C, Yoshida E, Shafran SD, Towner WJ, Tran TT, McNally J, Osinusi A, Svarovskaia E, Zhu Y, Brainard DM, McHutchison JG, Agarwal K, Zeuzem S; ASTRAL-1 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med. 2015 Dec 31;373(27):2599-607. doi: 10.1056/NEJMoa1512610. Epub 2015 Nov 16.</citation>
    <PMID>26571066</PMID>
  </reference>
  <reference>
    <citation>Feld JJ, Moreno C, Trinh R, Tam E, Bourgeois S, Horsmans Y, Elkhashab M, Bernstein DE, Younes Z, Reindollar RW, Larsen L, Fu B, Howieson K, Polepally AR, Pangerl A, Shulman NS, Poordad F. Sustained virologic response of 100% in HCV genotype 1b patients with cirrhosis receiving ombitasvir/paritaprevir/r and dasabuvir for 12weeks. J Hepatol. 2016 Feb;64(2):301-307. doi: 10.1016/j.jhep.2015.10.005. Epub 2015 Oct 22.</citation>
    <PMID>26476290</PMID>
  </reference>
  <reference>
    <citation>Foster GR, Afdhal N, Roberts SK, Brau N, Gane EJ, Pianko S, Lawitz E, Thompson A, Shiffman ML, Cooper C, Towner WJ, Conway B, Ruane P, Bourliere M, Asselah T, Berg T, Zeuzem S, Rosenberg W, Agarwal K, Stedman CA, Mo H, Dvory-Sobol H, Han L, Wang J, McNally J, Osinusi A, Brainard DM, McHutchison JG, Mazzotta F, Tran TT, Gordon SC, Patel K, Reau N, Mangia A, Sulkowski M; ASTRAL-2 Investigators; ASTRAL-3 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med. 2015 Dec 31;373(27):2608-17. doi: 10.1056/NEJMoa1512612. Epub 2015 Nov 17.</citation>
    <PMID>26575258</PMID>
  </reference>
  <reference>
    <citation>Younossi ZM, Stepanova M, Sulkowski M, Foster GR, Reau N, Mangia A, Patel K, Brau N, Roberts SK, Afdhal N, Nader F, Henry L, Hunt S. Ribavirin-Free Regimen With Sofosbuvir and Velpatasvir Is Associated With High Efficacy and Improvement of Patient-Reported Outcomes in Patients With Genotypes 2 and 3 Chronic Hepatitis C: Results From Astral-2 and -3 Clinical Trials. Clin Infect Dis. 2016 Oct 15;63(8):1042-1048. doi: 10.1093/cid/ciw496. Epub 2016 Jul 20.</citation>
    <PMID>27444413</PMID>
  </reference>
  <reference>
    <citation>Agarwal K, Castells L, Mullhaupt B, Rosenberg WMC, McNabb B, Arterburn S, Camus G, McNally J, Stamm LM, Brainard DM, Mani Subramanian G, Marino Z, Dufour JF, Forns X. Sofosbuvir/velpatasvir for 12 weeks in genotype 1-4 HCV-infected liver transplant recipients. J Hepatol. 2018 Sep;69(3):603-607. doi: 10.1016/j.jhep.2018.05.039. Epub 2018 Jun 8.</citation>
    <PMID>29886154</PMID>
  </reference>
  <reference>
    <citation>Reau N, Kwo PY, Rhee S, Brown RS Jr, Agarwal K, Angus P, Gane E, Kao JH, Mantry PS, Mutimer D, Reddy KR, Tran TT, Hu YB, Gulati A, Krishnan P, Dumas EO, Porcalla A, Shulman NS, Liu W, Samanta S, Trinh R, Forns X. Glecaprevir/Pibrentasvir Treatment in Liver or Kidney Transplant Patients With Hepatitis C Virus Infection. Hepatology. 2018 Oct;68(4):1298-1307. doi: 10.1002/hep.30046. Epub 2018 Jul 25.</citation>
    <PMID>29672891</PMID>
  </reference>
  <reference>
    <citation>Durand CM, Bowring MG, Brown DM, Chattergoon MA, Massaccesi G, Bair N, Wesson R, Reyad A, Naqvi FF, Ostrander D, Sugarman J, Segev DL, Sulkowski M, Desai NM. Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus-Infected Donors to Noninfected Recipients: An Open-Label Nonrandomized Trial. Ann Intern Med. 2018 Apr 17;168(8):533-540. doi: 10.7326/M17-2871. Epub 2018 Mar 6.</citation>
    <PMID>29507971</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 11, 2019</study_first_posted>
  <results_first_submitted>April 14, 2023</results_first_submitted>
  <results_first_submitted_qc>August 30, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">September 13, 2023</results_first_posted>
  <last_update_submitted>August 30, 2023</last_update_submitted>
  <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ohio State University</investigator_affiliation>
    <investigator_full_name>Reem Daloul</investigator_full_name>
    <investigator_title>Assistant Professor of Clinical Medicine, Transplant Nephrology</investigator_title>
  </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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sofosbuvir</mesh_term>
    <mesh_term>Sofosbuvir-velpatasvir drug combination</mesh_term>
    <mesh_term>Velpatasvir</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 14, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/07/NCT03801707/Prot_SAP_ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>54 Kidney transplant candidates were enrolled and listed on the Deceased Donor Kidney Wait-list to receive hepatitis C virus (HCV) viremic kidneys</recruitment_details>
      <pre_assignment_details>In total 18 patients were removed from the study: 9 participants received hepatitis C virus nucleic antigen test (HCV NAT) negative kidney transplants, 8 participants were removed from the kidney transplant deceased waiting-list, and 1 participant died prior to receiving kidney transplant</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Intervention Group</title>
          <description>kidney transplant recipients who receive kidney allograft from hepatitis C viremic donors followed by treatment with direct acting antiviral therapies.&#xD;
Sofosbuvir / Velpatasvir Oral Tablet [Epclusa]: fixed dose combination medication once a day for 12 weeks for the treatment of hepatitis C&#xD;
Glecaprevir/Pibrentasvir 100 MG-40 MG Oral Tablet [MAVYRET]: Three tablets once a day for 12 weeks for treatment of hepatitis C</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Removed from study due to reaching the study target of 30 transplant from hepatitis C viremic donors</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Intervention Group</title>
          <description>kidney transplant recipients who receive kidney allograft from hepatitis C viremic donors followed by treatment with direct acting antiviral therapies.&#xD;
Sofosbuvir / Velpatasvir Oral Tablet [Epclusa]: fixed dose combination medication once a day for 12 weeks for the treatment of hepatitis C&#xD;
Glecaprevir/Pibrentasvir 100 MG-40 MG Oral Tablet [MAVYRET]: Three tablets once a day for 12 weeks for treatment of hepatitis C</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="30"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59" lower_limit="51" upper_limit="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Primary cause of end stage kidney diseaes</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Diabetes Mellitus</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Hypertension</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Adult polycystic kidney disease</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Immunoglobin (IgA) nephropathy</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Others</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Time on dialysis prior to transplant</title>
          <units>months</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12" lower_limit="8" upper_limit="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Donor (D) -Recipient (R) Cytomegalovirus (CMV) status</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Cytomegalovirus (CMV) Donor (D)+/ Recipient (R-)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>CMV D+/R+</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>CMV D-/R+</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>CMV D-/R-</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Insurance type</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Public, Medicaid</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Public, Medicare</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Private</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pre-Transplant Calculated Panel Reactive Antibody (cPRA) %</title>
          <units>percent</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0" lower_limit="0" upper_limit="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Patients With Undetectable Hepatitis C Virus (HCV) Polymerase Chain Reaction (PCR) at 12 Weeks After Completion of HCV Treatment</title>
        <description>Proportion of patients with undetectable hepatitis C virus (HCV) polymerase chain reaction (PCR) at 12 weeks after completion of HCV treatment was to test the efficacy of the treatment.</description>
        <time_frame>12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intervention Group</title>
            <description>kidney transplant recipients who receive kidney allograft from hepatitis C viremic donors followed by treatment with direct acting antiviral therapies.&#xD;
Sofosbuvir / Velpatasvir Oral Tablet [Epclusa]: fixed dose combination medication once a day for 12 weeks for the treatment of hepatitis C&#xD;
Glecaprevir/Pibrentasvir 100 MG-40 MG Oral Tablet [MAVYRET]: Three tablets once a day for 12 weeks for treatment of hepatitis C</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Patients With Undetectable Hepatitis C Virus (HCV) Polymerase Chain Reaction (PCR) at 12 Weeks After Completion of HCV Treatment</title>
          <description>Proportion of patients with undetectable hepatitis C virus (HCV) polymerase chain reaction (PCR) at 12 weeks after completion of HCV treatment was to test the efficacy of the treatment.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Elevation in Liver Enzyme &gt;5 Times the Upper Limits, Development of Acute Cholestatic Hepatitis , or Intolerance to Direct Acting Antiviral Therapies</title>
        <description>Elevation in liver enzyme &gt;5 times the upper limits, development of acute cholestatic hepatitis , or intolerance to Direct acting antiviral therapies was to test the safety of utilizing HepC positive kidneys for transplant.</description>
        <time_frame>12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intervention Group</title>
            <description>kidney transplant recipients who receive kidney allograft from hepatitis C viremic donors followed by treatment with direct acting antiviral therapies.&#xD;
Sofosbuvir / Velpatasvir Oral Tablet [Epclusa]: fixed dose combination medication once a day for 12 weeks for the treatment of hepatitis C&#xD;
Glecaprevir/Pibrentasvir 100 MG-40 MG Oral Tablet [MAVYRET]: Three tablets once a day for 12 weeks for treatment of hepatitis C</description>
          </group>
        </group_list>
        <measure>
          <title>Elevation in Liver Enzyme &gt;5 Times the Upper Limits, Development of Acute Cholestatic Hepatitis , or Intolerance to Direct Acting Antiviral Therapies</title>
          <description>Elevation in liver enzyme &gt;5 times the upper limits, development of acute cholestatic hepatitis , or intolerance to Direct acting antiviral therapies was to test the safety of utilizing HepC positive kidneys for transplant.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Liver enzyme elevation &gt; 5 times upper limit</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Acute cholestatic hepatitis</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Medication intolerance to Direct Acting Antiviral</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No significant adverse effect reported</title>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Estimated Glomerular Filtration Rate (eGFR) at 6 and 12 Months Post-transplant</title>
        <description>Estimated glomerular filtration rate (eGFR) at 6 and 12 months post-transplant was to test the safety of utilizing of HepC positive kidneys.</description>
        <time_frame>6 and 12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intervention Group</title>
            <description>kidney transplant recipients who receive kidney allograft from hepatitis C viremic donors followed by treatment with direct acting antiviral therapies.&#xD;
Sofosbuvir / Velpatasvir Oral Tablet [Epclusa]: fixed dose combination medication once a day for 12 weeks for the treatment of hepatitis C&#xD;
Glecaprevir/Pibrentasvir 100 MG-40 MG Oral Tablet [MAVYRET]: Three tablets once a day for 12 weeks for treatment of hepatitis C</description>
          </group>
        </group_list>
        <measure>
          <title>Estimated Glomerular Filtration Rate (eGFR) at 6 and 12 Months Post-transplant</title>
          <description>Estimated glomerular filtration rate (eGFR) at 6 and 12 months post-transplant was to test the safety of utilizing of HepC positive kidneys.</description>
          <units>ml/min/1.73m^2</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>eGFR at 6 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54" lower_limit="41" upper_limit="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>eGFR at 12 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46" lower_limit="40" upper_limit="63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient's Survival at 6 and 12 Months</title>
        <description>Patient's survival at 6 and 12 months measuring safety of utilizing of HepC positive kidneys.</description>
        <time_frame>6 and 12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intervention Group</title>
            <description>kidney transplant recipients who receive kidney allograft from hepatitis C viremic donors followed by treatment with direct acting antiviral therapies.&#xD;
Sofosbuvir / Velpatasvir Oral Tablet [Epclusa]: fixed dose combination medication once a day for 12 weeks for the treatment of hepatitis C&#xD;
Glecaprevir/Pibrentasvir 100 MG-40 MG Oral Tablet [MAVYRET]: Three tablets once a day for 12 weeks for treatment of hepatitis C</description>
          </group>
        </group_list>
        <measure>
          <title>Patient's Survival at 6 and 12 Months</title>
          <description>Patient's survival at 6 and 12 months measuring safety of utilizing of HepC positive kidneys.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>6 months patient survival</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 months patient survival</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Graft Survival at 6 and 12 Months</title>
        <description>Graft survival at 6 and 12 months measuring safety of utilizing HepC positive kidneys.</description>
        <time_frame>12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intervention Group</title>
            <description>kidney transplant recipients who receive kidney allograft from hepatitis C viremic donors followed by treatment with direct acting antiviral therapies.&#xD;
Sofosbuvir / Velpatasvir Oral Tablet [Epclusa]: fixed dose combination medication once a day for 12 weeks for the treatment of hepatitis C&#xD;
Glecaprevir/Pibrentasvir 100 MG-40 MG Oral Tablet [MAVYRET]: Three tablets once a day for 12 weeks for treatment of hepatitis C</description>
          </group>
        </group_list>
        <measure>
          <title>Graft Survival at 6 and 12 Months</title>
          <description>Graft survival at 6 and 12 months measuring safety of utilizing HepC positive kidneys.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>6 months graft survival</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 months graft survival</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>25 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Intervention Group</title>
          <description>kidney transplant recipients who receive kidney allograft from hepatitis C viremic donors followed by treatment with direct acting antiviral therapies.&#xD;
Sofosbuvir / Velpatasvir Oral Tablet [Epclusa]: fixed dose combination medication once a day for 12 weeks for the treatment of hepatitis C&#xD;
Glecaprevir/Pibrentasvir 100 MG-40 MG Oral Tablet [MAVYRET]: Three tablets once a day for 12 weeks for treatment of hepatitis C</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Liver enzyme elevation</sub_title>
                <description>liver enzyme elevation &gt; 5 upper normal limit occurred in two patients. one patient prior to initiation of direct acting antiviral therapy, one patient during recurrence of HCV viremia in the setting of resistant mutation</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Brenda Cuson</name_or_title>
      <organization>The Ohio State University</organization>
      <phone>614-293-6883</phone>
      <email>Brenda.Cuson@osumc.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03801707
org study id: 2018H0499
nct id: NCT03801707
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
To evaluate the safety and feasibility of transplanting kidneys from Hepatitis C virus (HCV)
      infected donors into recipients without HCV infection
This will be an open label, prospective, interventional, proof of concept study to evaluate
      the feasibility and safety of kidney transplant from HCV positive donors into HCV negative
      recipients using treatment with pan-genotypic direct acting antiviral therapies (DAAS) for
      treatment of post-transplant HCV transmission
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of Patients With Undetectable Hepatitis C Virus (HCV) Polymerase Chain Reaction (PCR) at 12 Weeks After Completion of HCV Treatment
time frame: 12 weeks
description: Proportion of patients with undetectable hepatitis C virus (HCV) polymerase chain reaction (PCR) at 12 weeks after completion of HCV treatment was to test the efficacy of the treatment.
measure: Elevation in Liver Enzyme >5 Times the Upper Limits, Development of Acute Cholestatic Hepatitis , or Intolerance to Direct Acting Antiviral Therapies
time frame: 12 weeks
description: Elevation in liver enzyme >5 times the upper limits, development of acute cholestatic hepatitis , or intolerance to Direct acting antiviral therapies was to test the safety of utilizing HepC positive kidneys for transplant.
measure: Estimated Glomerular Filtration Rate (eGFR) at 6 and 12 Months Post-transplant
time frame: 6 and 12 months
description: Estimated glomerular filtration rate (eGFR) at 6 and 12 months post-transplant was to test the safety of utilizing of HepC positive kidneys.
measure: Patient's Survival at 6 and 12 Months
time frame: 6 and 12 months
description: Patient's survival at 6 and 12 months measuring safety of utilizing of HepC positive kidneys.
measure: Graft Survival at 6 and 12 Months
time frame: 12 months
description: Graft survival at 6 and 12 months measuring safety of utilizing HepC positive kidneys.
arm group label: Intervention group
arm group type: Experimental
description: kidney transplant recipients who receive kidney allograft from hepatitis C viremic donors followed by treatment with direct acting antiviral therapies.
intervention type: Drug
intervention name: Sofosbuvir / Velpatasvir Oral Tablet [Epclusa]
description: fixed dose combination medication once a day for 12 weeks for the treatment of hepatitis C
arm group label: Intervention group
other name: Epclusa
intervention type: Drug
intervention name: Glecaprevir/Pibrentasvir 100 MG-40 MG Oral Tablet [MAVYRET]
description: Three tablets once a day for 12 weeks for treatment of hepatitis C
arm group label: Intervention group
other name: Mavyret
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Reem Daloul, MD
role: Principal Investigator
affiliation: Ohio State University School of Biomedical Science: The Ohio State University College of Medicine
facility: 
country: United States
url: https://www.usrds.org/annual-data-report/current-adr/
description: USRDS Annual Data Report 2017
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: Curry MP, O'Leary JG, Bzowej N, Muir AJ, Korenblat KM, Fenkel JM, Reddy KR, Lawitz E, Flamm SL, Schiano T, Teperman L, Fontana R, Schiff E, Fried M, Doehle B, An D, McNally J, Osinusi A, Brainard DM, McHutchison JG, Brown RS Jr, Charlton M; ASTRAL-4 Investigators. Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis. N Engl J Med. 2015 Dec 31;373(27):2618-28. doi: 10.1056/NEJMoa1512614. Epub 2015 Nov 16.
PMID: 26569658
citation: Feld JJ, Jacobson IM, Hezode C, Asselah T, Ruane PJ, Gruener N, Abergel A, Mangia A, Lai CL, Chan HL, Mazzotta F, Moreno C, Yoshida E, Shafran SD, Towner WJ, Tran TT, McNally J, Osinusi A, Svarovskaia E, Zhu Y, Brainard DM, McHutchison JG, Agarwal K, Zeuzem S; ASTRAL-1 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med. 2015 Dec 31;373(27):2599-607. doi: 10.1056/NEJMoa1512610. Epub 2015 Nov 16.
PMID: 26571066
citation: Feld JJ, Moreno C, Trinh R, Tam E, Bourgeois S, Horsmans Y, Elkhashab M, Bernstein DE, Younes Z, Reindollar RW, Larsen L, Fu B, Howieson K, Polepally AR, Pangerl A, Shulman NS, Poordad F. Sustained virologic response of 100% in HCV genotype 1b patients with cirrhosis receiving ombitasvir/paritaprevir/r and dasabuvir for 12weeks. J Hepatol. 2016 Feb;64(2):301-307. doi: 10.1016/j.jhep.2015.10.005. Epub 2015 Oct 22.
PMID: 26476290
citation: Foster GR, Afdhal N, Roberts SK, Brau N, Gane EJ, Pianko S, Lawitz E, Thompson A, Shiffman ML, Cooper C, Towner WJ, Conway B, Ruane P, Bourliere M, Asselah T, Berg T, Zeuzem S, Rosenberg W, Agarwal K, Stedman CA, Mo H, Dvory-Sobol H, Han L, Wang J, McNally J, Osinusi A, Brainard DM, McHutchison JG, Mazzotta F, Tran TT, Gordon SC, Patel K, Reau N, Mangia A, Sulkowski M; ASTRAL-2 Investigators; ASTRAL-3 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med. 2015 Dec 31;373(27):2608-17. doi: 10.1056/NEJMoa1512612. Epub 2015 Nov 17.
PMID: 26575258
citation: Younossi ZM, Stepanova M, Sulkowski M, Foster GR, Reau N, Mangia A, Patel K, Brau N, Roberts SK, Afdhal N, Nader F, Henry L, Hunt S. Ribavirin-Free Regimen With Sofosbuvir and Velpatasvir Is Associated With High Efficacy and Improvement of Patient-Reported Outcomes in Patients With Genotypes 2 and 3 Chronic Hepatitis C: Results From Astral-2 and -3 Clinical Trials. Clin Infect Dis. 2016 Oct 15;63(8):1042-1048. doi: 10.1093/cid/ciw496. Epub 2016 Jul 20.
PMID: 27444413
citation: Agarwal K, Castells L, Mullhaupt B, Rosenberg WMC, McNabb B, Arterburn S, Camus G, McNally J, Stamm LM, Brainard DM, Mani Subramanian G, Marino Z, Dufour JF, Forns X. Sofosbuvir/velpatasvir for 12 weeks in genotype 1-4 HCV-infected liver transplant recipients. J Hepatol. 2018 Sep;69(3):603-607. doi: 10.1016/j.jhep.2018.05.039. Epub 2018 Jun 8.
PMID: 29886154
citation: Reau N, Kwo PY, Rhee S, Brown RS Jr, Agarwal K, Angus P, Gane E, Kao JH, Mantry PS, Mutimer D, Reddy KR, Tran TT, Hu YB, Gulati A, Krishnan P, Dumas EO, Porcalla A, Shulman NS, Liu W, Samanta S, Trinh R, Forns X. Glecaprevir/Pibrentasvir Treatment in Liver or Kidney Transplant Patients With Hepatitis C Virus Infection. Hepatology. 2018 Oct;68(4):1298-1307. doi: 10.1002/hep.30046. Epub 2018 Jul 25.
PMID: 29672891
citation: Durand CM, Bowring MG, Brown DM, Chattergoon MA, Massaccesi G, Bair N, Wesson R, Reyad A, Naqvi FF, Ostrander D, Sugarman J, Segev DL, Sulkowski M, Desai NM. Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus-Infected Donors to Noninfected Recipients: An Open-Label Nonrandomized Trial. Ann Intern Med. 2018 Apr 17;168(8):533-540. doi: 10.7326/M17-2871. Epub 2018 Mar 6.
PMID: 29507971
responsible party type: Principal Investigator
investigator affiliation: Ohio State University
investigator full name: Reem Daloul
investigator title: Assistant Professor of Clinical Medicine, Transplant Nephrology
mesh term: Hepatitis A
mesh term: Hepatitis C
mesh term: Hepatitis
mesh term: Sofosbuvir
mesh term: Sofosbuvir-velpatasvir drug combination
mesh term: Velpatasvir
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 