<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/NCT04444843</url>
  </required_header>
  <id_info>
    <org_study_id>ML40754</org_study_id>
    <nct_id>NCT04444843</nct_id>
  </id_info>
  <brief_title>Risk Factors of Chinese Kidney Transplant Recipients DSA Based on MPA Immunosuppressive Regimen</brief_title>
  <official_title>A Multicenter Clinical Trial: Risk Factors of Chinese Kidney Transplant Recipients DSA Based on MPA Immunosuppressive Regimen</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>First Affiliated Hospital Xi'an Jiaotong University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>First Affiliated Hospital Xi'an Jiaotong University</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>
      THE INCIDENCE AND INFLUENTIAL FACTORS OF DSA IN CHINESE RENAL TRANSPLANT RECIPIENTS WITH&#xD;
      MPA-BASED IMMUNOSUPPRESSIVE REGIMEN： A MULTI-CENTER CLINICAL STUDY (TIAIFOD STUDY)&#xD;
&#xD;
      Study procedure Investigators at participating centers will identify patients fulfilling&#xD;
      inclusion criteria and do not violate any exclusion criteria. Informed consent will be&#xD;
      obtained upon entry into the study according to national regulations. Patients will be&#xD;
      enrolled into the study and clinical data of patient history will be collected. Clinical data&#xD;
      will be collected prospectively up to a total period of 12 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Medical history and Kidney transplantation This will include age at transplantation, gender,&#xD;
      race, weight, height of both recipient and donor; Recipients: previous history ,BMI ,primary&#xD;
      kidney disease including biopsy proven diagnosis (if present), historic dialysis，pregnancy&#xD;
      history (female). Donor: the catalogue (DCD,DBD,DBCD), ECD or not，the cause of death,&#xD;
      received CPR or not; zero biopsy results if done, ABO blood type match, HLA-MM, cold and warm&#xD;
      ischemic time.&#xD;
&#xD;
      Clinical data at baseline and 12months follow up period:&#xD;
&#xD;
      Clinical assessments, laboratory, comorbidity, immunosuppressive therapy, and selected&#xD;
      concomitant therapy (anti-hypertension anti-hyperlipidemics, anti-diabetics and drugs known&#xD;
      to affect renal function) will be collected at transplant day（Day 0, visit 0）and 8 subsequent&#xD;
      visits scheduled Day 3, Week1, Week2, Week 4，Week 12，Week 26，Week 40，Week 52 post&#xD;
      transplantation. MPA-AUC, acute rejection episodes and graft loss will be collected at visits&#xD;
      scheduled Day 3, Week 1，Week 2, Week 4，Week 12， Week 26(6 month)，Week 40，Week 52 (12 month)&#xD;
      post transplantation. On day 3, MPA-AUC will be tested by full time sample&#xD;
      (0h,0.5h,1h,2h,3h,4h,6h,8h,10h,12h post receiving MMF). LSS (0h, 0.5h, 2h post receiving MMF)&#xD;
      will be used for testing MPA-AUC on other visits. PRA will be tested on week 4, week 12, week&#xD;
      26, week 52. If PRA is positive, DSA will be tested following once. All the PRA and DSA MFI&#xD;
      and phenotype will be collected（including the clinical-drive test）.&#xD;
&#xD;
      Statistical analysis:&#xD;
&#xD;
      The primary endpoint in this study is the incidence of DSA formation in 12-months&#xD;
      post-transplantation in Chinese kidney transplant recipients with MMF-based IS regimen. The&#xD;
      proportion and its 95% CI will be provided.&#xD;
&#xD;
      The influential factors of DSA formation will be estimated using logistic regression&#xD;
      including relevant influential factors, where the influential factors are defined as {age,&#xD;
      gender of donor / recipients recipient: BMI, blood transfusion, previous AR （before DSA&#xD;
      appears）, ECD , cold ischemia time, HLA-MM, Tac trough concentration, MPA-AUC, DGF,&#xD;
      introduction therapy (including use or not and the drugs )}. .&#xD;
&#xD;
      The full MPA-AUC0-12h will be calculated using the trapezoidal rule. The calculated formula&#xD;
      with Limited Sample Strategy (LSS) will be established to predict the MPA-AUC0-12h in the&#xD;
      Chinese patients. Correlation coefficients will be calculated and multiple stepwise&#xD;
      regression analysis will be used to determine the time points and best equation for&#xD;
      evaluating MPA-AUC0-12h.&#xD;
&#xD;
      Estimates for the time-to-event variable(s), such as Overall Survival(OS), will be obtained&#xD;
      by using the Kaplan-Meier (KM) approach together with associated 95% CI.&#xD;
&#xD;
      The other secondary endpoints will be summarized descriptively depended on the variable type.&#xD;
      The comparison between patients with and without DSA-positive will be performed according to&#xD;
      the variable type.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 22, 2021</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 21, 2022</primary_completion_date>
  <phase>Phase 4</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>
    <intervention_model_description>To estimate the incidence of DSA formation during 12-months post-transplantation</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>the incidence of Donor specific antibody(DSA) formation during 12-months post-transplantation</measure>
    <time_frame>12-months</time_frame>
    <description>the incidence of DSA formation during 12-months post-transplantation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>the incidence of DSA formation during 6-months post-transplantation</measure>
    <time_frame>6 months</time_frame>
    <description>the incidence of DSA formation during 6-months post-transplantation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the influential factors of DSA formation</measure>
    <time_frame>12 months</time_frame>
    <description>the influential factors of DSA formation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the association between DSA and MPA AUC</measure>
    <time_frame>12 months</time_frame>
    <description>the association between DSA and MPA AUC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the calculation formula for MPA-AUC with ISS using multiple regression analysis</measure>
    <time_frame>12 months</time_frame>
    <description>the calculation formula for MPA-AUC with ISS using multiple regression analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the proportion of patients experiencing Acute Rejection(AR), Biopsy proven acute rejection(BPAR), Antibody mediated rejection(ABMR) and the association with Donor specific antibody(DSA)</measure>
    <time_frame>12 months</time_frame>
    <description>the proportion of patients experiencing AR, BPAR, ABMR and the association with DSA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the renal function (Calculated creatinine clearance) at 12 month and association with DSA</measure>
    <time_frame>12 months</time_frame>
    <description>the renal function (Calculated creatinine clearance) at 12 month and association with DSA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the death-censored graft survival rate at 12 month post transplantation and association with Donor specific antibody(DSA)</measure>
    <time_frame>12 months</time_frame>
    <description>the death-censored graft survival rate and association with Donor specific antibody(DSA)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Kidney Transplant Recipients</condition>
  <arm_group>
    <arm_group_label>Mycophenolate Mofetil Capsules</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>The dosage of mycophenolate mofetil (CellCept) will be decided by the investigator and should be adjusted according to clinical response or therapeutic drug monitoring. It is not allowed to switch to other MPAs. When MMF is discontinued but is not switched to other MPA, the patients will be followed until the end of study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mycophenolate Mofetil Capsules</intervention_name>
    <description>Patients who received MMF+TAC+ Corticosteroids immunosuppressive regimen as first choice post transplantation</description>
    <arm_group_label>Mycophenolate Mofetil Capsules</arm_group_label>
    <other_name>Other MPAs</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female kidney transplant recipients from 18 to 65 years of age (including 18 &amp;&#xD;
             65 years old patients)&#xD;
&#xD;
          -  Single organ and first kidney transplant recipients from donation after citizen's&#xD;
             death&#xD;
&#xD;
          -  Patients who received MMF+TAC+ Corticosteroids immunosuppressive regimen as first&#xD;
             choice post transplantation&#xD;
&#xD;
          -  Pre-transplant PRA is negative (0%)&#xD;
&#xD;
          -  One serum pregnancy test with a sensitivity of at least 25mlU/Ml for patients of&#xD;
             childbearing potential before enrolled. A second test should be performed 8-10 days&#xD;
             later. Repeat pregnancy tests should be performed during routine follow-up visits.&#xD;
             Results of all pregnancy tests should be discussed with the patient. Patients should&#xD;
             be instructed to consult their physician immediately should pregnancy occur. For&#xD;
             patients to be included in the study, negative result must be obtained. And highly&#xD;
             effective contraception for women of childbearing potential. Contraception must be&#xD;
             taken before beginning study drug therapy, during therapy and for 6 weeks after the&#xD;
             last dose of study medication&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Patients who do not receive MMF&#xD;
&#xD;
          -  Patients who are re-transplantation or multiple organ transplantation recipients&#xD;
&#xD;
          -  Female patients who are pregnant or lactating&#xD;
&#xD;
          -  Patients who have any form of substance abuse, psychological illness or any other&#xD;
             condition, which, in the opinion of the investigator, may interfere with the patient's&#xD;
             ability to understand the requirements of the study.&#xD;
&#xD;
          -  Patients who would have received another investigational drug within 30 days preceding&#xD;
             the enrollment, received prohibited immunosuppressant medications prior to transplant&#xD;
&#xD;
          -  Patients who are using AZA, MTX, CTX or will use these drugs post-transplantation&#xD;
&#xD;
          -  Known contraindications to TAC , corticosteroids, MMF&#xD;
&#xD;
          -  Patients who have active peptic ulcer&#xD;
&#xD;
          -  Patients who have severe cardiac or lung disease&#xD;
&#xD;
          -  Patient who have active hepatica disease&#xD;
&#xD;
          -  Patients who have a history of cancer, except successfully treated localized&#xD;
             nonmelanocytic skin cancer&#xD;
&#xD;
          -  Patients who would not be available for routine study visits or follow-up, or not&#xD;
             being followed by an accredited laboratory.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wujun Xue, Prof.</last_name>
    <role>Study Chair</role>
    <affiliation>First Affiliated Hospital Xi'an Jiaotong University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Wujun Xue, Prof.</last_name>
    <phone>+86 13991990128</phone>
    <email>xwujun163@mail.xjtu.edu.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jin Zheng, Prof.</last_name>
    <phone>+86 18133916118</phone>
    <email>jzheng@mail.xjtu.edu.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>First Affiliated Hospital Xi'an Jiaotong University</name>
      <address>
        <city>Xi'an</city>
        <state>Shaanxi</state>
        <zip>710000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jin Zheng</last_name>
      <phone>+86 18133916118</phone>
      <email>jzheng@mail.xjtu.edu.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
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  </results_reference>
  <results_reference>
    <citation>van Gelder T, Silva HT, de Fijter JW, Budde K, Kuypers D, Tyden G, Lohmus A, Sommerer C, Hartmann A, Le Meur Y, Oellerich M, Holt DW, Tonshoff B, Keown P, Campbell S, Mamelok RD. Comparing mycophenolate mofetil regimens for de novo renal transplant recipients: the fixed-dose concentration-controlled trial. Transplantation. 2008 Oct 27;86(8):1043-51. doi: 10.1097/TP.0b013e318186f98a.</citation>
    <PMID>18946341</PMID>
  </results_reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 24, 2020</study_first_posted>
  <last_update_submitted>May 25, 2022</last_update_submitted>
  <last_update_submitted_qc>May 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>kidney transplant recipients</keyword>
  <keyword>Mycophenolate Mofetil Capsules</keyword>
  <keyword>Acute Rejection</keyword>
  <keyword>Cyclosporine</keyword>
  <keyword>Delayed graft function</keyword>
  <keyword>Tacrolimus</keyword>
  <keyword>Mycophenolic Acid Area under the Curve</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycophenolic Acid</mesh_term>
  </intervention_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/NCT04444843
org study id: ML40754
nct id: NCT04444843
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
THE INCIDENCE AND INFLUENTIAL FACTORS OF DSA IN CHINESE RENAL TRANSPLANT RECIPIENTS WITH
      MPA-BASED IMMUNOSUPPRESSIVE REGIMEN： A MULTI-CENTER CLINICAL STUDY (TIAIFOD STUDY)

      Study procedure Investigators at participating centers will identify patients fulfilling
      inclusion criteria and do not violate any exclusion criteria. Informed consent will be
      obtained upon entry into the study according to national regulations. Patients will be
      enrolled into the study and clinical data of patient history will be collected. Clinical data
      will be collected prospectively up to a total period of 12 months.
Medical history and Kidney transplantation This will include age at transplantation, gender,
      race, weight, height of both recipient and donor; Recipients: previous history ,BMI ,primary
      kidney disease including biopsy proven diagnosis (if present), historic dialysis，pregnancy
      history (female). Donor: the catalogue (DCD,DBD,DBCD), ECD or not，the cause of death,
      received CPR or not; zero biopsy results if done, ABO blood type match, HLA-MM, cold and warm
      ischemic time.

      Clinical data at baseline and 12months follow up period:

      Clinical assessments, laboratory, comorbidity, immunosuppressive therapy, and selected
      concomitant therapy (anti-hypertension anti-hyperlipidemics, anti-diabetics and drugs known
      to affect renal function) will be collected at transplant day（Day 0, visit 0）and 8 subsequent
      visits scheduled Day 3, Week1, Week2, Week 4，Week 12，Week 26，Week 40，Week 52 post
      transplantation. MPA-AUC, acute rejection episodes and graft loss will be collected at visits
      scheduled Day 3, Week 1，Week 2, Week 4，Week 12， Week 26(6 month)，Week 40，Week 52 (12 month)
      post transplantation. On day 3, MPA-AUC will be tested by full time sample
      (0h,0.5h,1h,2h,3h,4h,6h,8h,10h,12h post receiving MMF). LSS (0h, 0.5h, 2h post receiving MMF)
      will be used for testing MPA-AUC on other visits. PRA will be tested on week 4, week 12, week
      26, week 52. If PRA is positive, DSA will be tested following once. All the PRA and DSA MFI
      and phenotype will be collected（including the clinical-drive test）.

      Statistical analysis:

      The primary endpoint in this study is the incidence of DSA formation in 12-months
      post-transplantation in Chinese kidney transplant recipients with MMF-based IS regimen. The
      proportion and its 95% CI will be provided.

      The influential factors of DSA formation will be estimated using logistic regression
      including relevant influential factors, where the influential factors are defined as {age,
      gender of donor / recipients recipient: BMI, blood transfusion, previous AR （before DSA
      appears）, ECD , cold ischemia time, HLA-MM, Tac trough concentration, MPA-AUC, DGF,
      introduction therapy (including use or not and the drugs )}. .

      The full MPA-AUC0-12h will be calculated using the trapezoidal rule. The calculated formula
      with Limited Sample Strategy (LSS) will be established to predict the MPA-AUC0-12h in the
      Chinese patients. Correlation coefficients will be calculated and multiple stepwise
      regression analysis will be used to determine the time points and best equation for
      evaluating MPA-AUC0-12h.

      Estimates for the time-to-event variable(s), such as Overall Survival(OS), will be obtained
      by using the Kaplan-Meier (KM) approach together with associated 95% CI.

      The other secondary endpoints will be summarized descriptively depended on the variable type.
      The comparison between patients with and without DSA-positive will be performed according to
      the variable type.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: To estimate the incidence of DSA formation during 12-months post-transplantation
primary purpose: Treatment
masking: None (Open Label)
measure: the incidence of Donor specific antibody(DSA) formation during 12-months post-transplantation
time frame: 12-months
description: the incidence of DSA formation during 12-months post-transplantation
measure: the incidence of DSA formation during 6-months post-transplantation
time frame: 6 months
description: the incidence of DSA formation during 6-months post-transplantation
measure: the influential factors of DSA formation
time frame: 12 months
description: the influential factors of DSA formation
measure: the association between DSA and MPA AUC
time frame: 12 months
description: the association between DSA and MPA AUC
measure: the calculation formula for MPA-AUC with ISS using multiple regression analysis
time frame: 12 months
description: the calculation formula for MPA-AUC with ISS using multiple regression analysis
measure: the proportion of patients experiencing Acute Rejection(AR), Biopsy proven acute rejection(BPAR), Antibody mediated rejection(ABMR) and the association with Donor specific antibody(DSA)
time frame: 12 months
description: the proportion of patients experiencing AR, BPAR, ABMR and the association with DSA
measure: the renal function (Calculated creatinine clearance) at 12 month and association with DSA
time frame: 12 months
description: the renal function (Calculated creatinine clearance) at 12 month and association with DSA
measure: the death-censored graft survival rate at 12 month post transplantation and association with Donor specific antibody(DSA)
time frame: 12 months
description: the death-censored graft survival rate and association with Donor specific antibody(DSA)
arm group label: Mycophenolate Mofetil Capsules
arm group type: Other
description: The dosage of mycophenolate mofetil (CellCept) will be decided by the investigator and should be adjusted according to clinical response or therapeutic drug monitoring. It is not allowed to switch to other MPAs. When MMF is discontinued but is not switched to other MPA, the patients will be followed until the end of study.
intervention type: Drug
intervention name: Mycophenolate Mofetil Capsules
description: Patients who received MMF+TAC+ Corticosteroids immunosuppressive regimen as first choice post transplantation
arm group label: Mycophenolate Mofetil Capsules
other name: Other MPAs
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Wujun Xue, Prof.
role: Study Chair
affiliation: First Affiliated Hospital Xi'an Jiaotong University
last name: Wujun Xue, Prof.
phone: +86 13991990128
email: xwujun163@mail.xjtu.edu.cn
last name: Jin Zheng, Prof.
phone: +86 18133916118
email: jzheng@mail.xjtu.edu.cn
facility: 
status: Recruiting
contact: 
country: China
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PMID: 18946341
responsible party type: Sponsor
mesh term: Mycophenolic Acid