<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/NCT02974686</url>
  </required_header>
  <id_info>
    <org_study_id>201603167</org_study_id>
    <secondary_id>CRAD001AUS209T</secondary_id>
    <nct_id>NCT02974686</nct_id>
  </id_info>
  <brief_title>Conversion From MPA to Zortress (Everolimus) for GI Toxicity Post-renal Transplantation</brief_title>
  <official_title>Conversion From MPA to Zortress (Everolimus) for GI Toxicity Post-renal Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients who receive renal transplantation at Barnes Jewish Hospital (BJH) are placed on&#xD;
      triple maintenance immunosuppression, which means that patients take 3 types of&#xD;
      immunosuppression drugs to suppress their immune system including tacrolimus, mycophenolate&#xD;
      (MPA), and prednisone. However, due to the effects of MPA on the gastrointestinal tract,&#xD;
      patients often complain of GI adverse effects. Current practice is to either dose-reduce MPA&#xD;
      or convert the patient to an alternative agent, typically Azathioprine. Both of these&#xD;
      strategies have limitations, largely due to concerns related to efficacy. Everolimus (EVR)&#xD;
      has demonstrated similar efficacy to MPA in renal transplantation and may offer a benefit&#xD;
      related to GI adverse effects, so the investigators will convert patients to EVR in this&#xD;
      study. Patients who are within their first year post-transplant will be converted to EVR upon&#xD;
      enrollment in the study, and serial measurements ,or a series of measurements looking for an&#xD;
      increase or decrease over time, of GI adverse effects will be conducted over 1 year&#xD;
      post-enrollment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    low recruitment&#xD;
  </why_stopped>
  <start_date type="Actual">November 2016</start_date>
  <completion_date type="Actual">September 2019</completion_date>
  <primary_completion_date type="Actual">September 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Gastrointestinal Symptom Rating Scale</measure>
    <time_frame>3 months</time_frame>
    <description>Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Gastrointestinal Symptom Rating Scale</measure>
    <time_frame>1, 6, and 12 months</time_frame>
    <description>Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biopsy Proven Acute Rejection</measure>
    <time_frame>12 months</time_frame>
    <description>Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Kidney Transplant Rejection</condition>
  <condition>Gastrointestinal Disorder, Functional</condition>
  <arm_group>
    <arm_group_label>Interventional (EVR)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients experiencing gastrointestinal adverse effects in the first year post transplant will be converted from mycophenolate to everolimus</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Prior Agent (MPA)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patient will have baseline data collected while on MPA for comparison with EVR</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Everolimus</intervention_name>
    <arm_group_label>Interventional (EVR)</arm_group_label>
    <other_name>Zortress</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mycophenolic Acid</intervention_name>
    <arm_group_label>Prior Agent (MPA)</arm_group_label>
    <other_name>Cellcept</other_name>
    <other_name>Myfortic</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Kidney transplant recipients at Washington University/Barnes-Jewish Hospital&#xD;
&#xD;
          2. Experiencing GI toxicity from MPA as determined by the treating physician within 12&#xD;
             months post-renal transplant&#xD;
&#xD;
          3. On standard immunosuppression with tacrolimus and prednisone&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Dual organ or kidney after another solid organ transplant&#xD;
&#xD;
          2. Presence of a preexisting significant GI condition that does not have a presumed&#xD;
             causal relationship with MPA&#xD;
&#xD;
          3. Evidence of any GI disorder induced by an infection, underlying medical condition, or&#xD;
             concomitant medication other than MPA&#xD;
&#xD;
          4. Estimated glomerular filtration rate (eGFR) &lt;40 ml/min at time of possible conversion&#xD;
&#xD;
          5. Proteinuria &gt;1 gram/day at time of possible conversion&#xD;
&#xD;
          6. Profound bone marrow suppression at the time of possible conversion as defined as:&#xD;
&#xD;
               -  Hemoglobin &lt;10 g/dL&#xD;
&#xD;
               -  White blood cell (WBC) &lt; 3 K/cumm&#xD;
&#xD;
               -  Platelets &lt;100 K/cumm&#xD;
&#xD;
          7. Wound healing issues at time of possible conversion (eg, wound dehiscence, wound&#xD;
             infection, incisional hernia, lymphocele, seroma)&#xD;
&#xD;
          8. Elevated total cholesterol (&gt;350 mg/dL) and/or triglycerides (&gt;500 ng/dL) at time of&#xD;
             possible conversion&#xD;
&#xD;
          9. Hypersensitivity to everolimus, sirolimus, or other rapamycin derivatives&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>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>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>November 3, 2016</study_first_submitted>
  <study_first_submitted_qc>November 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2016</study_first_posted>
  <results_first_submitted>June 26, 2020</results_first_submitted>
  <results_first_submitted_qc>August 7, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">August 10, 2020</results_first_posted>
  <last_update_submitted>August 7, 2020</last_update_submitted>
  <last_update_submitted_qc>August 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 10, 2020</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>Gastrointestinal Diseases</mesh_term>
    <mesh_term>Digestive System Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycophenolic Acid</mesh_term>
    <mesh_term>Everolimus</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</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>May 31, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/86/NCT02974686/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Interventional Everolimus (EVR)</title>
          <description>Patients experiencing gastrointestinal adverse effects in the first year post transplant will be converted from mycophenolate to everolimus&#xD;
Everolimus</description>
        </group>
        <group group_id="P2">
          <title>Prior Agent Mycophenolic Acid (MPA)</title>
          <description>Patient will have baseline data collected while on MPA for comparison with EVR&#xD;
Mycophenolic Acid</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.</population>
      <group_list>
        <group group_id="B1">
          <title>Interventional (EVR)</title>
          <description>Patients experiencing gastrointestinal adverse effects in the first year post transplant will be converted from mycophenolate to everolimus&#xD;
Everolimus</description>
        </group>
        <group group_id="B2">
          <title>Prior Agent (MPA)</title>
          <description>Patient will have baseline data collected while on MPA for comparison with EVR&#xD;
Mycophenolic Acid</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="0"/>
            <count group_id="B2" value="0"/>
            <count group_id="B3" value="0"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                </category>
                <category>
                  <title>Male</title>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                </category>
                <category>
                  <title>Asian</title>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                </category>
                <category>
                  <title>Black or African American</title>
                </category>
                <category>
                  <title>White</title>
                </category>
                <category>
                  <title>More than one race</title>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <class_list>
            <class>
              <title>United States</title>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Gastrointestinal Symptom Rating Scale</title>
        <description>Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.</description>
        <time_frame>3 months</time_frame>
        <population>Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.</population>
        <group_list>
          <group group_id="O1">
            <title>Interventional (EVR)</title>
            <description>Patients experiencing gastrointestinal adverse effects in the first year post transplant will be converted from mycophenolate to everolimus&#xD;
Everolimus</description>
          </group>
          <group group_id="O2">
            <title>Prior Agent (MPA)</title>
            <description>Patient will have baseline data collected while on MPA for comparison with EVR&#xD;
Mycophenolic Acid</description>
          </group>
        </group_list>
        <measure>
          <title>Gastrointestinal Symptom Rating Scale</title>
          <description>Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.</description>
          <population>Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Gastrointestinal Symptom Rating Scale</title>
        <description>Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.</description>
        <time_frame>1, 6, and 12 months</time_frame>
        <population>Trial was terminated with only 1 participant enrolled, no data is reported to protect patient confidentiality</population>
        <group_list>
          <group group_id="O1">
            <title>Interventional (EVR)</title>
            <description>Patients experiencing gastrointestinal adverse effects in the first year post transplant will be converted from mycophenolate to everolimus&#xD;
Everolimus</description>
          </group>
          <group group_id="O2">
            <title>Prior Agent (MPA)</title>
            <description>Patient will have baseline data collected while on MPA for comparison with EVR&#xD;
Mycophenolic Acid</description>
          </group>
        </group_list>
        <measure>
          <title>Gastrointestinal Symptom Rating Scale</title>
          <description>Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.</description>
          <population>Trial was terminated with only 1 participant enrolled, no data is reported to protect patient confidentiality</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Biopsy Proven Acute Rejection</title>
        <description>Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.</description>
        <time_frame>12 months</time_frame>
        <population>Trial was terminated with only 1 participant enrolled, no data is reported to protect patient confidentiality</population>
        <group_list>
          <group group_id="O1">
            <title>Interventional Everolimus (EVR)</title>
            <description>Patients experiencing gastrointestinal adverse effects in the first year post transplant will be converted from mycophenolate to everolimus&#xD;
Everolimus</description>
          </group>
          <group group_id="O2">
            <title>Prior Agent Mycophenolic Acid (MPA)</title>
            <description>Patient will have baseline data collected while on MPA for comparison with EVR&#xD;
Mycophenolic Acid</description>
          </group>
        </group_list>
        <measure>
          <title>Biopsy Proven Acute Rejection</title>
          <description>Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.</description>
          <population>Trial was terminated with only 1 participant enrolled, no data is reported to protect patient confidentiality</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.</time_frame>
      <desc>Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.</desc>
      <group_list>
        <group group_id="E1">
          <title>Interventional (EVR)</title>
          <description>Patients experiencing gastrointestinal adverse effects in the first year post transplant will be converted from mycophenolate to everolimus&#xD;
Everolimus</description>
        </group>
        <group group_id="E2">
          <title>Prior Agent (MPA)</title>
          <description>Patient will have baseline data collected while on MPA for comparison with EVR&#xD;
Mycophenolic Acid</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="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>
    <limitations_and_caveats>Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. R. Delos Santos</name_or_title>
      <organization>Washington University</organization>
      <phone>314-362-8351</phone>
      <email>delossantos@wustl.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/NCT02974686
org study id: 201603167
secondary id: CRAD001AUS209T
nct id: NCT02974686
lead sponsor: 
collaborator: 
has dmc: Yes
Patients who receive renal transplantation at Barnes Jewish Hospital (BJH) are placed on
      triple maintenance immunosuppression, which means that patients take 3 types of
      immunosuppression drugs to suppress their immune system including tacrolimus, mycophenolate
      (MPA), and prednisone. However, due to the effects of MPA on the gastrointestinal tract,
      patients often complain of GI adverse effects. Current practice is to either dose-reduce MPA
      or convert the patient to an alternative agent, typically Azathioprine. Both of these
      strategies have limitations, largely due to concerns related to efficacy. Everolimus (EVR)
      has demonstrated similar efficacy to MPA in renal transplantation and may offer a benefit
      related to GI adverse effects, so the investigators will convert patients to EVR in this
      study. Patients who are within their first year post-transplant will be converted to EVR upon
      enrollment in the study, and serial measurements ,or a series of measurements looking for an
      increase or decrease over time, of GI adverse effects will be conducted over 1 year
      post-enrollment.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Gastrointestinal Symptom Rating Scale
time frame: 3 months
description: Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.
measure: Gastrointestinal Symptom Rating Scale
time frame: 1, 6, and 12 months
description: Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.
measure: Biopsy Proven Acute Rejection
time frame: 12 months
description: Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.
arm group label: Interventional (EVR)
arm group type: Active Comparator
description: Patients experiencing gastrointestinal adverse effects in the first year post transplant will be converted from mycophenolate to everolimus
arm group label: Prior Agent (MPA)
arm group type: Active Comparator
description: Patient will have baseline data collected while on MPA for comparison with EVR
intervention type: Drug
intervention name: Everolimus
arm group label: Interventional (EVR)
other name: Zortress
intervention type: Drug
intervention name: Mycophenolic Acid
arm group label: Prior Agent (MPA)
other name: Cellcept
other name: Myfortic
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Gastrointestinal Diseases
mesh term: Digestive System Diseases
mesh term: Mycophenolic Acid
mesh term: Everolimus
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.
point of contact: 