<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/NCT03800576</url>
  </required_header>
  <id_info>
    <org_study_id>201812015RINC</org_study_id>
    <nct_id>NCT03800576</nct_id>
  </id_info>
  <brief_title>Clinical Outcome of Liver Transplant Patients With Tacrolimus-based Immunosuppression</brief_title>
  <official_title>The Influence of Genetic and Clinical Factors on Clinical Outcome of Liver Transplant Patients With Tacrolimus-based Immunosuppression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</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>
      Genetic polymorphism and numerous clinical factors could influence tacrolimus&#xD;
      pharmacokinetics, which led to large inter-and intra-individual variability.Since its narrow&#xD;
      therapeutic range,predicting therapeutic outcome and individualized dosage remains to be a&#xD;
      challenge. The study's objective is to identify the genetic and clinical factors that can&#xD;
      influence clinical outcome in liver transplant.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A great number of studies had found significant correlation between tacrolimus&#xD;
      pharmacokinetics and gene polymorphism. However, previous studies on the correlation between&#xD;
      genetic factors and clinical outcome were controversial. Furthermore, most studies focused on&#xD;
      single genetic polymorphism and clinical outcome, and very limited studies took multiple&#xD;
      genetic factors and clinical factors into account.&#xD;
&#xD;
      This is a retrospective study. Eligible patients were those who had signed informed consent&#xD;
      for genetic study in previous research projects ( IRB approval number：201512005RINC and&#xD;
      201612023RIND ). The present study will collect laboratory data, concurrent medications, and&#xD;
      therapeutic drug monitoring (TDM) data. Patient survival, graft survival, acute rejection and&#xD;
      tacrolimus-associated adverse events will be assessed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 6, 2019</start_date>
  <completion_date type="Actual">September 22, 2020</completion_date>
  <primary_completion_date type="Actual">October 8, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of patients with biopsy proven acute rejection (BPAR)</measure>
    <time_frame>up to 12 months after liver transplantation</time_frame>
    <description>Incidence of BPAR will be estimated with Kaplan-Meier analysis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Graft survival</measure>
    <time_frame>up to 9 years after liver transplantation</time_frame>
    <description>incidence of graft loss will be estimated Kaplan-Meier analysis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with tacrolimus-associated adverse events</measure>
    <time_frame>up to 9 years after liver transplantation</time_frame>
    <description>Common adverse events of tacrolimus such as nephrotoxicity, post-transplant diabetes mellitus, hypertension, infection, hyperlipidemia and malignancy.&#xD;
nephrotoxicity：decreased renal function estimated by glomerular filtration rate(GFR) using MDRD 4-Variable Equation&#xD;
Post-transplant diabetes mellitus：defined by diagnosis and the use of antihyperglycemic agents, laboratory data including blood sugar(mg/dL) and hemoglobin A1c (percentage)&#xD;
hypertension：defined by diagnosis and the use of antihypertensive agents, laboratory data including blood pressure(mmHg)&#xD;
infection：defined by diagnosis of infection and the use of antiinfective agents&#xD;
Hyperlipidemia：defined by diagnosis and the use of lipid-lowering agents, laboratory data including LDL (mg/dL), HDL (mg/dL) and total cholesterol (mg/dL)&#xD;
malignancy：incidence of cancer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient survival</measure>
    <time_frame>up to 9 years after liver transplantation</time_frame>
    <description>incidence of death</description>
  </secondary_outcome>
  <enrollment type="Actual">113</enrollment>
  <condition>Liver Transplantation</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Patients who underwent living donor liver transplantation (LDLT) during 2008 to 2017 in&#xD;
        National Taiwan University Hospital and received tacrolimus-based immunosuppression.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Eligible patients were those who had signed informed consent for genetic study in our&#xD;
        previous research projects.&#xD;
&#xD;
        Inclusion Criteria of the Previous Study:&#xD;
&#xD;
          -  patients who underwent living-donor liver transplantation during January 2008 to&#xD;
             December 2017&#xD;
&#xD;
          -  at the age of 20-65&#xD;
&#xD;
          -  with tacrolimus-based immunosuppression after liver transplant for at least 6 months.&#xD;
&#xD;
        Exclusion Criteria of the Previous Study :&#xD;
&#xD;
          -  retransplantation&#xD;
&#xD;
          -  multi-organ transplantation&#xD;
&#xD;
          -  human immunodeficiency virus (HIV) positive.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rey-Heng Hu, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Taiwan University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 9, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 11, 2019</study_first_posted>
  <last_update_submitted>March 14, 2021</last_update_submitted>
  <last_update_submitted_qc>March 14, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>tacrolimus</keyword>
  <keyword>liver transplant</keyword>
  <keyword>gene polymorphism</keyword>
  <keyword>immunosuppressant</keyword>
  <!-- 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/NCT03800576
org study id: 201812015RINC
nct id: NCT03800576
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Genetic polymorphism and numerous clinical factors could influence tacrolimus
      pharmacokinetics, which led to large inter-and intra-individual variability.Since its narrow
      therapeutic range,predicting therapeutic outcome and individualized dosage remains to be a
      challenge. The study's objective is to identify the genetic and clinical factors that can
      influence clinical outcome in liver transplant.
A great number of studies had found significant correlation between tacrolimus
      pharmacokinetics and gene polymorphism. However, previous studies on the correlation between
      genetic factors and clinical outcome were controversial. Furthermore, most studies focused on
      single genetic polymorphism and clinical outcome, and very limited studies took multiple
      genetic factors and clinical factors into account.

      This is a retrospective study. Eligible patients were those who had signed informed consent
      for genetic study in previous research projects ( IRB approval number：201512005RINC and
      201612023RIND ). The present study will collect laboratory data, concurrent medications, and
      therapeutic drug monitoring (TDM) data. Patient survival, graft survival, acute rejection and
      tacrolimus-associated adverse events will be assessed.
observational model: Case-Only
time perspective: Retrospective
measure: Incidence of patients with biopsy proven acute rejection (BPAR)
time frame: up to 12 months after liver transplantation
description: Incidence of BPAR will be estimated with Kaplan-Meier analysis
measure: Graft survival
time frame: up to 9 years after liver transplantation
description: incidence of graft loss will be estimated Kaplan-Meier analysis
measure: Number of patients with tacrolimus-associated adverse events
time frame: up to 9 years after liver transplantation
description: Common adverse events of tacrolimus such as nephrotoxicity, post-transplant diabetes mellitus, hypertension, infection, hyperlipidemia and malignancy.
nephrotoxicity：decreased renal function estimated by glomerular filtration rate(GFR) using MDRD 4-Variable Equation
Post-transplant diabetes mellitus：defined by diagnosis and the use of antihyperglycemic agents, laboratory data including blood sugar(mg/dL) and hemoglobin A1c (percentage)
hypertension：defined by diagnosis and the use of antihypertensive agents, laboratory data including blood pressure(mmHg)
infection：defined by diagnosis of infection and the use of antiinfective agents
Hyperlipidemia：defined by diagnosis and the use of lipid-lowering agents, laboratory data including LDL (mg/dL), HDL (mg/dL) and total cholesterol (mg/dL)
malignancy：incidence of cancer
measure: Patient survival
time frame: up to 9 years after liver transplantation
description: incidence of death
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 20 Years
maximum age: 65 Years
healthy volunteers: No
last name: Rey-Heng Hu, Professor
role: Principal Investigator
affiliation: National Taiwan University Hospital
facility: 
country: Taiwan
responsible party type: Sponsor