<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/NCT01706471</url>
  </required_header>
  <id_info>
    <org_study_id>4-2009-0109</org_study_id>
    <nct_id>NCT01706471</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of the Early Introduction of Everolimus (Certican®) With Low Dose of Cyclosporine in de Novo Kidney Recipients After 1 Month of Transplantation</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yonsei University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yonsei University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Calcineurin inhibitors, such as cyclosporine and tacrolimus, have improved allograft survival&#xD;
      in kidney organ transplantation. Indeed, they have reduced the incidence of acute rejection&#xD;
      episodes of cadaveric allograft recipients. Although marked progression has been made in&#xD;
      initial survival rates, long-term kidney graft survival has yet to show such encouraging&#xD;
      results. Because CNIs are associated with adverse effects, particularly nephrotoxicity, which&#xD;
      contribute to declining organ function and eventual graft loss. In kidney transplants,&#xD;
      progressive allograft dysfunction has been shown to develop in as many as 94% of patients by&#xD;
      1 year.&#xD;
&#xD;
      Therefore, reducing or eliminating the dose of CNIs to minimize nephrotoxicity must be&#xD;
      balanced against the maintenance of adequate immunosuppression.&#xD;
&#xD;
      Certican allows CNI dose reduction then provides renal function improvement and current PSI&#xD;
      strategy point out that early intervention is important in managing the risk of CAN before it&#xD;
      develops in both de novo and maintenance renal transplant recipients.&#xD;
&#xD;
      To demonstrate Certican early introduction after 1 month provides better renal function with&#xD;
      no change of efficacy compared to standard regimen, and also prevent delayed wound healing.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2009</start_date>
  <completion_date type="Actual">April 2013</completion_date>
  <primary_completion_date type="Actual">January 2013</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Reduced Exposure Cyclosporine in Renal Transplant Recipients</measure>
    <time_frame>12 months after the time of kidney transplantation</time_frame>
    <description>A 12-month, multi center, randomized, open-label, non-inferiority study of efficacy and safety comparing early introduction of Certican® after 1 month and standard regimen in de novo renal transplant recipients</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Planned Kidney Transplantation</condition>
  <arm_group>
    <arm_group_label>Everolimus + Low dose CsA +PD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Myfortic+ Standard CsA + PD</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Everolimus + Low dose CsA +PD</intervention_name>
    <description>Group A : Initiation of 5mg/kg bid Neoral dose and 720mg bid Myfortic and then adjusting Neoral targeting 150-200ng. After 1 month reduce Neoral dose as following table and Certican starting 0.75mg bid then adjust Certican 3-8ng/ml. Myfortic continue until Certican trough level goes up &gt;3 ng/mL. Steroid dose follows local protocol.</description>
    <arm_group_label>Everolimus + Low dose CsA +PD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Myfortic+ Standard CsA + PD</intervention_name>
    <description>Group B : Initiation of 5mg/kg bid Neoral dose and 720mg bid Myfortic and then adjusting Neoral targeting 150-200ng/ml. After 1 month reduce Neoral dose targeting 100-200ng with no change of Myfortic dose. Steroid dose follows local protocol.</description>
    <arm_group_label>Myfortic+ Standard CsA + PD</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males or Females aged 18~65 years&#xD;
&#xD;
          2. De novo recipients of cadaveric, living unrelated or living related donor kidney&#xD;
             transplants&#xD;
&#xD;
          3. Received kidney transplant from aged 10~65years donor&#xD;
&#xD;
          4. Willing to provide written informed consent&#xD;
&#xD;
          5. Completing study visits according to study protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Recipients of multiple organ transplants&#xD;
&#xD;
          2. Kidney transplant from non-heart beating cadaveric donor / organ donor after cardiac&#xD;
             death&#xD;
&#xD;
          3. Recipients of A-B-O incompatible transplants or lymphocyte cross-match positive&#xD;
             transplants&#xD;
&#xD;
          4. Recipients of extra-renal solid organ transplants or stem cell transplants&#xD;
&#xD;
          5. Recipient/ donor who are known to have anti-HCV, HIV or HBsAg positive&#xD;
&#xD;
          6. Diagnosed as Cancer within the past 5 years (except complete recovered squamous cell&#xD;
             or basal cell skin cancer)&#xD;
&#xD;
          7. Drug Hypersensitivity to investigational drugs or related drugs Females are pregnant&#xD;
             and lactating&#xD;
&#xD;
          8. Any of the following laboratory abnormalities at screening:&#xD;
&#xD;
               -  ALT, AST, ALP, total bilirubin &gt; 3 times the upper limit&#xD;
&#xD;
               -  ANC &lt; 1,500mm3 or WBC &lt; 2,500mm3 or platelet &lt; 100,000 mm3&#xD;
&#xD;
               -  Cholesterol &gt; 350 mg/dl or 9.0 mmol/L, TG &gt; 500 mg/dl or 5.6mmol/L&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Department of Surgery, Yonsei University College of Medicine, Severance Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>120-752</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>February 2014</verification_date>
  <study_first_submitted>October 8, 2012</study_first_submitted>
  <study_first_submitted_qc>October 11, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2012</study_first_posted>
  <last_update_submitted>February 17, 2014</last_update_submitted>
  <last_update_submitted_qc>February 17, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 19, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>verLowCNI</keyword>
  <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>
  <!-- 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/NCT01706471
org study id: 4-2009-0109
nct id: NCT01706471
lead sponsor: 
has dmc: No
Calcineurin inhibitors, such as cyclosporine and tacrolimus, have improved allograft survival
      in kidney organ transplantation. Indeed, they have reduced the incidence of acute rejection
      episodes of cadaveric allograft recipients. Although marked progression has been made in
      initial survival rates, long-term kidney graft survival has yet to show such encouraging
      results. Because CNIs are associated with adverse effects, particularly nephrotoxicity, which
      contribute to declining organ function and eventual graft loss. In kidney transplants,
      progressive allograft dysfunction has been shown to develop in as many as 94% of patients by
      1 year.

      Therefore, reducing or eliminating the dose of CNIs to minimize nephrotoxicity must be
      balanced against the maintenance of adequate immunosuppression.

      Certican allows CNI dose reduction then provides renal function improvement and current PSI
      strategy point out that early intervention is important in managing the risk of CAN before it
      develops in both de novo and maintenance renal transplant recipients.

      To demonstrate Certican early introduction after 1 month provides better renal function with
      no change of efficacy compared to standard regimen, and also prevent delayed wound healing.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Reduced Exposure Cyclosporine in Renal Transplant Recipients
time frame: 12 months after the time of kidney transplantation
description: A 12-month, multi center, randomized, open-label, non-inferiority study of efficacy and safety comparing early introduction of Certican® after 1 month and standard regimen in de novo renal transplant recipients
arm group label: Everolimus + Low dose CsA +PD
arm group type: Experimental
arm group label: Myfortic+ Standard CsA + PD
arm group type: Active Comparator
intervention type: Drug
intervention name: Everolimus + Low dose CsA +PD
description: Group A : Initiation of 5mg/kg bid Neoral dose and 720mg bid Myfortic and then adjusting Neoral targeting 150-200ng. After 1 month reduce Neoral dose as following table and Certican starting 0.75mg bid then adjust Certican 3-8ng/ml. Myfortic continue until Certican trough level goes up >3 ng/mL. Steroid dose follows local protocol.
arm group label: Everolimus + Low dose CsA +PD
intervention type: Drug
intervention name: Myfortic+ Standard CsA + PD
description: Group B : Initiation of 5mg/kg bid Neoral dose and 720mg bid Myfortic and then adjusting Neoral targeting 150-200ng/ml. After 1 month reduce Neoral dose targeting 100-200ng with no change of Myfortic dose. Steroid dose follows local protocol.
arm group label: Myfortic+ Standard CsA + PD
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Mycophenolic Acid
mesh term: Everolimus