<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/NCT03751332</url>
  </required_header>
  <id_info>
    <org_study_id>1.05</org_study_id>
    <secondary_id>154/01/2008</secondary_id>
    <nct_id>NCT03751332</nct_id>
  </id_info>
  <brief_title>The Vienna Prograf and Endothelial Progenitor Cell Extension Study</brief_title>
  <acronym>PEP-X</acronym>
  <official_title>The Vienna Prograf and Endothelial Progenitor Cell Extension Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Vienna</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Vienna</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>
      Conversion of renal transplant recipients from either tacrolimus or cyclosporin A to&#xD;
      tacrolimus modified release to investigate the effects of the MDR1/CYP450 genotype on the&#xD;
      trough blood levels of tacrolimus with modified galenic (tacrolimus MR4; Advagraf®).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study concerns the conversion of immunosuppressive agents among participants in the&#xD;
      clinical trial &quot;The Vienna Prograf and Endothelial Progenitor Cell Study - The Vienna PEP&#xD;
      Study&quot; at the end of the study after 2 years in the extension study PEP-X.&#xD;
&#xD;
      The aim of the conversion is to investigate the effects of the multi-drug resistance (MDR1,&#xD;
      gene symbol ABCB1) genotype on the trough blood levels of tacrolimus modified release (TAC&#xD;
      MR4; Advagraf®). Analyzes of the effects of the genotype on the concentration/dose ratio&#xD;
      ([ng/mL]/[mg/d]) will be carried out, as well as studies on existing polymorphisms in the&#xD;
      MDR1 gene. The written informed consent to conversion of either tacrolimus (TAC; Prograf®) or&#xD;
      cyclosporin A (CSA; Sandimmun Neoral®) to TAC MR4 will be obtained.&#xD;
&#xD;
      Upon completion of 24 months of study participation of the PEP-study, and consent to convert&#xD;
      the immunosuppressant therapy of either TAC or CSA to TAC MR4, it will be used as indicated&#xD;
      by the manufacturer. In patients treated with CSA, the initial dose will be 0.1-0.12 mg TAC&#xD;
      MR4 per kg of body weight per day with oral morning administration. In patients who are&#xD;
      already treated with TAC, the conversion to TAC MR4 will be performed in a 1:1 ratio.&#xD;
&#xD;
      The dosage data for the conversion of CSA to TAC MR4 are taken from the documents of the&#xD;
      European Medicines Agency homepage (http://www.emea.europa.eu/index/ indexh1.htm, retrieved&#xD;
      26.09.2007), those on the safety and equivalence of the achieved areas under the curve (AUC)&#xD;
      of both TAC formulations from Alloway et al. (Transplant Proc 2005; 37: 867-870).&#xD;
&#xD;
      The conversion will be performed by Univ. Prof. Dr. Gere Sunder-Plassmann, and Dr. Markus&#xD;
      Riegersperger, respectively, both Division of Nephrology and Dialysis, Department of Medicine&#xD;
      III, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna. The desired trough&#xD;
      level is set at 4.0-8.0ng/mL according to the usual clinical standards for long-term&#xD;
      transplant patients at the investigators center. The trough level analyses are performed at&#xD;
      the Medical University of Vienna, according to the following schedule: 1 week after&#xD;
      conversion, 2 weeks after conversion, 4 weeks after conversion, 12 weeks and 12 months after&#xD;
      conversion.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 2008</start_date>
  <completion_date type="Actual">October 2010</completion_date>
  <primary_completion_date type="Actual">October 2010</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effects of the MDR1 genotype on the trough blood levels of tacrolimus with modified galenics (tacrolimus MR4; Advagraf®)</measure>
    <time_frame>12 months</time_frame>
    <description>Effects of the genotype on the concentration/dose ratio ([ng/mL]/[mg/d])</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">87</enrollment>
  <condition>Immunosuppression</condition>
  <condition>Renal Failure</condition>
  <arm_group>
    <arm_group_label>Conversion from either CSA or TAC</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Tacrolimus with modified galenic (tacrolimus MR4; Advagraf®) once daily. In patients treated with ciclosporin A, the initial dose will be 0.1 - 0.12 mg tacrolimus MR4 per kg of body weight per day with oral morning administration. In patients who are already treated with Prograf, the conversion to Advagraf will be performed in a 1:1 ratio.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tacrolimus</intervention_name>
    <description>Conversion from either cyclosporin or tacrolimus to tacrolimus modified release</description>
    <arm_group_label>Conversion from either CSA or TAC</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Any stable long-term kidney transplant recipient who participated in the Vienna&#xD;
             Prograf and Endothelial-Progenitor Study (Vienna PEP Study; EudraCT identifier 2004-82&#xD;
             004209-98)&#xD;
&#xD;
          -  Written informed consent to have the immunosuppression converted from either&#xD;
             cyclosporin A or tacrolimus to tacrolimus modified-release&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Graft failure&#xD;
&#xD;
          -  Contraindication to receive immunosuppression&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gere Sunder-Plassmann, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of Vienna</affiliation>
  </overall_official>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 9, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>November 20, 2018</last_update_submitted>
  <last_update_submitted_qc>November 20, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Vienna</investigator_affiliation>
    <investigator_full_name>Gere Sunder-Plassmann</investigator_full_name>
    <investigator_title>Associated Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Calcineurin inhibitors</keyword>
  <keyword>Tacrolimus modified release</keyword>
  <keyword>Conversion</keyword>
  <keyword>Trough levels</keyword>
  <keyword>MDR-1</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Renal Insufficiency</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tacrolimus</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03751332
org study id: 1.05
secondary id: 154/01/2008
nct id: NCT03751332
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Conversion of renal transplant recipients from either tacrolimus or cyclosporin A to
      tacrolimus modified release to investigate the effects of the MDR1/CYP450 genotype on the
      trough blood levels of tacrolimus with modified galenic (tacrolimus MR4; Advagraf®).
The study concerns the conversion of immunosuppressive agents among participants in the
      clinical trial "The Vienna Prograf and Endothelial Progenitor Cell Study - The Vienna PEP
      Study" at the end of the study after 2 years in the extension study PEP-X.

      The aim of the conversion is to investigate the effects of the multi-drug resistance (MDR1,
      gene symbol ABCB1) genotype on the trough blood levels of tacrolimus modified release (TAC
      MR4; Advagraf®). Analyzes of the effects of the genotype on the concentration/dose ratio
      ([ng/mL]/[mg/d]) will be carried out, as well as studies on existing polymorphisms in the
      MDR1 gene. The written informed consent to conversion of either tacrolimus (TAC; Prograf®) or
      cyclosporin A (CSA; Sandimmun Neoral®) to TAC MR4 will be obtained.

      Upon completion of 24 months of study participation of the PEP-study, and consent to convert
      the immunosuppressant therapy of either TAC or CSA to TAC MR4, it will be used as indicated
      by the manufacturer. In patients treated with CSA, the initial dose will be 0.1-0.12 mg TAC
      MR4 per kg of body weight per day with oral morning administration. In patients who are
      already treated with TAC, the conversion to TAC MR4 will be performed in a 1:1 ratio.

      The dosage data for the conversion of CSA to TAC MR4 are taken from the documents of the
      European Medicines Agency homepage (http://www.emea.europa.eu/index/ indexh1.htm, retrieved
      26.09.2007), those on the safety and equivalence of the achieved areas under the curve (AUC)
      of both TAC formulations from Alloway et al. (Transplant Proc 2005; 37: 867-870).

      The conversion will be performed by Univ. Prof. Dr. Gere Sunder-Plassmann, and Dr. Markus
      Riegersperger, respectively, both Division of Nephrology and Dialysis, Department of Medicine
      III, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna. The desired trough
      level is set at 4.0-8.0ng/mL according to the usual clinical standards for long-term
      transplant patients at the investigators center. The trough level analyses are performed at
      the Medical University of Vienna, according to the following schedule: 1 week after
      conversion, 2 weeks after conversion, 4 weeks after conversion, 12 weeks and 12 months after
      conversion.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Effects of the MDR1 genotype on the trough blood levels of tacrolimus with modified galenics (tacrolimus MR4; Advagraf®)
time frame: 12 months
description: Effects of the genotype on the concentration/dose ratio ([ng/mL]/[mg/d])
arm group label: Conversion from either CSA or TAC
arm group type: Other
description: Tacrolimus with modified galenic (tacrolimus MR4; Advagraf®) once daily. In patients treated with ciclosporin A, the initial dose will be 0.1 - 0.12 mg tacrolimus MR4 per kg of body weight per day with oral morning administration. In patients who are already treated with Prograf, the conversion to Advagraf will be performed in a 1:1 ratio.
intervention type: Drug
intervention name: Tacrolimus
description: Conversion from either cyclosporin or tacrolimus to tacrolimus modified release
arm group label: Conversion from either CSA or TAC
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Gere Sunder-Plassmann, MD
role: Principal Investigator
affiliation: Medical University of Vienna
responsible party type: Principal Investigator
investigator affiliation: Medical University of Vienna
investigator full name: Gere Sunder-Plassmann
investigator title: Associated Professor of Medicine
mesh term: Renal Insufficiency
mesh term: Tacrolimus
sharing ipd: Undecided