<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/NCT03797196</url>
  </required_header>
  <id_info>
    <org_study_id>OPTIMIZE</org_study_id>
    <nct_id>NCT03797196</nct_id>
  </id_info>
  <brief_title>RCT Comparing Immunosuppressive Regimens in Elderly Renal Transplant Recipients</brief_title>
  <acronym>OPTIMIZE</acronym>
  <official_title>Open Label Multicenter Randomized Trial Comparing Standard Immunosuppression With Tacrolimus and Mycophenolate Mofetil With a Low Exposure Tacrolimus Regimen in Combination With Everolimus in de Novo Renal Transplantation in Elderly Patient</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Medical Center Groningen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Amsterdam UMC, location VUmc</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>UMC Utrecht</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Leiden University Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Erasmus Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Universitaire Ziekenhuizen KU Leuven</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Medical Center Groningen</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Open label, randomized, multicenter, intervention trial comparing standard immunosuppression&#xD;
      with tacrolimus and mycophenolate mofetil with a low exposure tacrolimus regimen in&#xD;
      combination with everolimus.&#xD;
&#xD;
      The primary objective is to test the hypothesis that an age-adapted immunosuppressive regimen&#xD;
      targeted at reduced immunosuppression with low calcineurin inhibitor (tacrolimus) exposure in&#xD;
      combination with everolimus will result in improved outcome in elderly recipients of A:&#xD;
      Kidneys from older deceased donors (&gt;64 years) and B: Kidneys from living donors (all ages)&#xD;
      and younger deceased donors (&lt;65 years).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study two immunosuppressive regimes will be tested; In both groups basiliximab&#xD;
      induction will be applied. Additionally, the standard therapy consisting of prednisolone,&#xD;
      mycophenolic acid and tacrolimus once-daily (Envarsus®), or the comparator in which&#xD;
      mycophenolic acid will be replaced by everolimus combined with strongly reduced levels of&#xD;
      tacrolimus once-daily (Envarsus®). When not tolerated,tacrolimus may be replaced by&#xD;
      ciclosporin. The hypothesis is that reduced calcineurin inhibitor (CNI) exposure in&#xD;
      combination with everolimus will lead to improved allograft function, a reduced incidence of&#xD;
      complications and improved quality of life.&#xD;
&#xD;
      This study will consist of two strata: Stratum A: Elderly recipients (≥65 years) of kidneys&#xD;
      from elderly deceased donors (≥65 years) within the Eurotransplant Senior Program. Stratum B:&#xD;
      Elderly recipients (≥65 years) of kidneys from living donors (all ages) or deceased donors&#xD;
      (&lt;65 years). The primary endpoint will be &quot;successful transplantation&quot; which is defined as&#xD;
      survival with a functioning allograft with a minimum estimated GFR of 30 ml/min per 1.73 m2&#xD;
      in stratum A and 45 ml/min per 1.73 m2 in stratum B, after 2 years.&#xD;
&#xD;
      The study will be performed by the Dutch transplant centers and the Dutch Kidney Patient&#xD;
      Organization (NVN) will participate.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 29, 2019</start_date>
  <completion_date type="Anticipated">December 2026</completion_date>
  <primary_completion_date type="Anticipated">June 2025</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>successful transplantation</measure>
    <time_frame>24 months</time_frame>
    <description>The overall primary study endpoint &quot;successful transplantation&quot; as defined for the individual strata and analyzed for the whole study population.&#xD;
Stratum A: Primary endpoint: successful transplantation at two years after transplantation defined as: absence of graft or patient loss in the presence of an eGFR above 30 ml/min/1.73m2.&#xD;
Stratum B: Primary endpoint: successful transplantation at two years after transplantation defined as absence of graft or patient loss in the presence of an eGFR above 45 ml/min/1.73m2</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>death</measure>
    <time_frame>24 months</time_frame>
    <description>patient survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>graft loss</measure>
    <time_frame>24 months</time_frame>
    <description>graft survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>acute rejection</measure>
    <time_frame>24 months</time_frame>
    <description>treated biopsy-proven rejection (tBPAR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>eGFR</measure>
    <time_frame>12 and 24 months</time_frame>
    <description>estimated Glomerular Filtration Rate below 30 and 45 ml/min/1.73m2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>type of rejection treatment</measure>
    <time_frame>24 months</time_frame>
    <description>type of rejection treatment will be scored by questionnaire to the treating nephrologist</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The evolution of renal function (eGFR) and creatinine clearance over time by slope analysis</measure>
    <time_frame>24 months</time_frame>
    <description>The evolution of renal function (eGFR) and creatinine clearance over time by slope analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of adverse events, serious adverse events and adverse reactions</measure>
    <time_frame>24 months</time_frame>
    <description>The incidence of adverse events, serious adverse events and adverse reactions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence of clinically relevant infections, post transplantation diabetes mellitus, malignancies and cardiovascular events</measure>
    <time_frame>24 months</time_frame>
    <description>The incidence of clinically relevant infections, post transplantation diabetes, malignancies and cardiovascular events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of frailty after transplantation and change in frailty from baseline frailty from baseline</measure>
    <time_frame>12 and 24 months</time_frame>
    <description>frailty is measured by clinical frailty score, hand grip strength and fried frailty index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical functioning and changes over time</measure>
    <time_frame>24 months</time_frame>
    <description>Short Physical Performance Battery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive functioning and changes over time</measure>
    <time_frame>24 months</time_frame>
    <description>Montreal Cognitive Assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of T-cell immunosenescence at 12 and 24 months and changes from baseline</measure>
    <time_frame>24 months</time_frame>
    <description>T cell differentiation, exhaustion and telomere length will be assessed by flowcytometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HRQoL at 0, 12 and 24 months and changes from baseline</measure>
    <time_frame>24 months</time_frame>
    <description>Questionnaire: EQ-5D and SF-12</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Development of donor-specific anti-HLA antibodies (DSA)</measure>
    <time_frame>24 months</time_frame>
    <description>DSA as measured by Luminex</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in illness perception at 0, 12 and 24 months and changes from baseline</measure>
    <time_frame>24 months</time_frame>
    <description>Questionnaire: Brief Illness Perception Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in adherence of immunosuppressive medication at 12 and 24 months</measure>
    <time_frame>24 months</time_frame>
    <description>Questionnaire: Basel Assessment of Adherence to Immunosuppressive Medication Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in symptoms at 0, 12 and 24 months and changes from baseline</measure>
    <time_frame>24 months</time_frame>
    <description>Questionnaire: Dialysis Symptom Index with additional items from the Modified Transplant Symptom Occurrence and Symptom Distress Scale-59</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in iBOX predicted outcome at 3, 5 and 7 years</measure>
    <time_frame>24 months</time_frame>
    <description>Based on the available data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Development of a pharmacokinetic model for tacrolimus once-daily (Envarsus®), using data on AUC's</measure>
    <time_frame>24 months</time_frame>
    <description>In addition to trough levels, additional AUC's will be withdrawn at the Leiden University Medical Center as routine patient care on week 2 and 6.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>o evaluate the response to the COIVD-19 vaccine and identify possible differences between both treatment groups at the University Medical Center Groningen.</measure>
    <time_frame>24 months</time_frame>
    <description>Humoral and T-cell response</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Evaluation of Cost-effectiveness of the new immunosuppressive regimen, and comparison to the current standard of care</measure>
    <time_frame>24 months</time_frame>
    <description>Cost-effectiveness of the immunosuppressive regimen will be evaluated using state-of-the-art health-economic techniques; costs and effectiveness of immunosuppressive therapy will be derived from the study</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">374</enrollment>
  <condition>Renal Transplant Recipients</condition>
  <condition>Elderly Patients</condition>
  <condition>Immunosuppression</condition>
  <arm_group>
    <arm_group_label>group 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>standard tacrolimus with mycophenolate mofetil</description>
  </arm_group>
  <arm_group>
    <arm_group_label>group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>low dose tacrolimus with everolimus</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>low dose tacrolimus in combination with everolimus</intervention_name>
    <description>a low exposure Tacrolimus once-daily (Envarsus®) regimen in combination with Everolimus will be evaluated in elderly transplant recipients</description>
    <arm_group_label>group 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>standard dose tacrolimus with mycophenolate mofetil</intervention_name>
    <description>A standard Tacrolimus once-daily (Envarsus) regimen in combination with Everolimus will be evaluated in elderly transplant recipients</description>
    <arm_group_label>group 1</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent must be obtained before any assessment is performed&#xD;
&#xD;
          2. Male or female subject ≥65 years old&#xD;
&#xD;
          3. Subject randomized within 24 hours of completion of transplant surgery&#xD;
&#xD;
          4. Stratum A: Recipient of a primary (or secondary, if first graft is not lost due to&#xD;
             immunological reasons) renal transplant from a deceased donor aged 65 years or older&#xD;
&#xD;
          5. Stratum B: Recipient of a primary (or secondary, if first graft is not lost due to&#xD;
             immunological reasons) renal transplant from a deceased donor aged below 65 years or a&#xD;
             living donor of any age&#xD;
&#xD;
        Exclusion Criteria: Exclusion criteria for both stratum A and B&#xD;
&#xD;
          1. Subject is a multi-organ transplant recipient&#xD;
&#xD;
          2. Recipient of bloodgroup ABO incompatible allograft or CDC cross-match positive&#xD;
             transplant&#xD;
&#xD;
          3. Subject at high immunological risk for rejection as determined by local practice for&#xD;
             assessment of anti-donor reactivity&#xD;
&#xD;
          4. Recipient of a kidney with a cold ischaemia time (CIT) &gt;24 hr&#xD;
&#xD;
          5. Recipients of a kidney from an HLA-identical related living donor&#xD;
&#xD;
          6. Known intolerability for one or more of the study drugs&#xD;
&#xD;
          7. Subject who is HIV positive&#xD;
&#xD;
          8. HBsAg and/or a HCV positive subject with evidence of elevated liver function tests&#xD;
             (ALT/AST levels ≥2.5 times ULN). Viral serology results obtained within 6 months prior&#xD;
             to randomization are acceptable&#xD;
&#xD;
          9. Recipient of a kidney from a donor who tests positive for human immunodeficiency&#xD;
             virus, (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV)&#xD;
&#xD;
         10. Subject with severe systemic infections, current or within the two weeks prior to&#xD;
             randomization&#xD;
&#xD;
         11. Subject with severe restrictive or obstructive pulmonary disorders&#xD;
&#xD;
         12. Subject with severe hypercholesterolemia or hypertriglyceridemia that cannot be&#xD;
             controlled&#xD;
&#xD;
         13. Subject with white blood cell (WBC) count ≤ 2,000/mm3 or with platelet count ≤&#xD;
             50,000/mm3&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dennis Hesselink, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>EMC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Frederike Bemelman, Md, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>AIDS Malignancy Consortium</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Stefan Berger, Md, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>UMCG</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jan-Stephan Sanders, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>UMCG</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Azam Nurmohamed, Md, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>VUMC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Aiko De Vries, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>LUMC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Luuk Hilbrands, Md, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Radboud MC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Arjan Van Zuilen, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UMCU</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Dirk Kuypers, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Leuven MC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Leuven University Hospital</name>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amsterdam UMC</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMCG</name>
      <address>
        <city>Groningen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LUMC</name>
      <address>
        <city>Leiden</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Radboud University Hospital</name>
      <address>
        <city>Nijmegen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erasmus MC</name>
      <address>
        <city>Rotterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMCU</name>
      <address>
        <city>Utrecht</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>December 11, 2018</study_first_submitted>
  <study_first_submitted_qc>January 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 9, 2019</study_first_posted>
  <last_update_submitted>May 9, 2023</last_update_submitted>
  <last_update_submitted_qc>May 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Medical Center Groningen</investigator_affiliation>
    <investigator_full_name>J.S.F. Sanders</investigator_full_name>
    <investigator_title>principal investigator, head of renal transplant program UMCG</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycophenolic Acid</mesh_term>
    <mesh_term>Everolimus</mesh_term>
    <mesh_term>Tacrolimus</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03797196
org study id: OPTIMIZE
nct id: NCT03797196
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Open label, randomized, multicenter, intervention trial comparing standard immunosuppression
      with tacrolimus and mycophenolate mofetil with a low exposure tacrolimus regimen in
      combination with everolimus.

      The primary objective is to test the hypothesis that an age-adapted immunosuppressive regimen
      targeted at reduced immunosuppression with low calcineurin inhibitor (tacrolimus) exposure in
      combination with everolimus will result in improved outcome in elderly recipients of A:
      Kidneys from older deceased donors (>64 years) and B: Kidneys from living donors (all ages)
      and younger deceased donors (<65 years).
In this study two immunosuppressive regimes will be tested; In both groups basiliximab
      induction will be applied. Additionally, the standard therapy consisting of prednisolone,
      mycophenolic acid and tacrolimus once-daily (Envarsus®), or the comparator in which
      mycophenolic acid will be replaced by everolimus combined with strongly reduced levels of
      tacrolimus once-daily (Envarsus®). When not tolerated,tacrolimus may be replaced by
      ciclosporin. The hypothesis is that reduced calcineurin inhibitor (CNI) exposure in
      combination with everolimus will lead to improved allograft function, a reduced incidence of
      complications and improved quality of life.

      This study will consist of two strata: Stratum A: Elderly recipients (≥65 years) of kidneys
      from elderly deceased donors (≥65 years) within the Eurotransplant Senior Program. Stratum B:
      Elderly recipients (≥65 years) of kidneys from living donors (all ages) or deceased donors
      (<65 years). The primary endpoint will be "successful transplantation" which is defined as
      survival with a functioning allograft with a minimum estimated GFR of 30 ml/min per 1.73 m2
      in stratum A and 45 ml/min per 1.73 m2 in stratum B, after 2 years.

      The study will be performed by the Dutch transplant centers and the Dutch Kidney Patient
      Organization (NVN) will participate.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: successful transplantation
time frame: 24 months
description: The overall primary study endpoint "successful transplantation" as defined for the individual strata and analyzed for the whole study population.
Stratum A: Primary endpoint: successful transplantation at two years after transplantation defined as: absence of graft or patient loss in the presence of an eGFR above 30 ml/min/1.73m2.
Stratum B: Primary endpoint: successful transplantation at two years after transplantation defined as absence of graft or patient loss in the presence of an eGFR above 45 ml/min/1.73m2
measure: death
time frame: 24 months
description: patient survival
measure: graft loss
time frame: 24 months
description: graft survival
measure: acute rejection
time frame: 24 months
description: treated biopsy-proven rejection (tBPAR)
measure: eGFR
time frame: 12 and 24 months
description: estimated Glomerular Filtration Rate below 30 and 45 ml/min/1.73m2
measure: type of rejection treatment
time frame: 24 months
description: type of rejection treatment will be scored by questionnaire to the treating nephrologist
measure: The evolution of renal function (eGFR) and creatinine clearance over time by slope analysis
time frame: 24 months
description: The evolution of renal function (eGFR) and creatinine clearance over time by slope analysis
measure: The incidence of adverse events, serious adverse events and adverse reactions
time frame: 24 months
description: The incidence of adverse events, serious adverse events and adverse reactions
measure: The incidence of clinically relevant infections, post transplantation diabetes mellitus, malignancies and cardiovascular events
time frame: 24 months
description: The incidence of clinically relevant infections, post transplantation diabetes, malignancies and cardiovascular events
measure: Presence of frailty after transplantation and change in frailty from baseline frailty from baseline
time frame: 12 and 24 months
description: frailty is measured by clinical frailty score, hand grip strength and fried frailty index
measure: Physical functioning and changes over time
time frame: 24 months
description: Short Physical Performance Battery
measure: Cognitive functioning and changes over time
time frame: 24 months
description: Montreal Cognitive Assessment
measure: Presence of T-cell immunosenescence at 12 and 24 months and changes from baseline
time frame: 24 months
description: T cell differentiation, exhaustion and telomere length will be assessed by flowcytometry
measure: HRQoL at 0, 12 and 24 months and changes from baseline
time frame: 24 months
description: Questionnaire: EQ-5D and SF-12
measure: Development of donor-specific anti-HLA antibodies (DSA)
time frame: 24 months
description: DSA as measured by Luminex
measure: Difference in illness perception at 0, 12 and 24 months and changes from baseline
time frame: 24 months
description: Questionnaire: Brief Illness Perception Questionnaire
measure: Difference in adherence of immunosuppressive medication at 12 and 24 months
time frame: 24 months
description: Questionnaire: Basel Assessment of Adherence to Immunosuppressive Medication Scale
measure: Difference in symptoms at 0, 12 and 24 months and changes from baseline
time frame: 24 months
description: Questionnaire: Dialysis Symptom Index with additional items from the Modified Transplant Symptom Occurrence and Symptom Distress Scale-59
measure: Difference in iBOX predicted outcome at 3, 5 and 7 years
time frame: 24 months
description: Based on the available data
measure: Development of a pharmacokinetic model for tacrolimus once-daily (Envarsus®), using data on AUC's
time frame: 24 months
description: In addition to trough levels, additional AUC's will be withdrawn at the Leiden University Medical Center as routine patient care on week 2 and 6.
measure: o evaluate the response to the COIVD-19 vaccine and identify possible differences between both treatment groups at the University Medical Center Groningen.
time frame: 24 months
description: Humoral and T-cell response
measure: Evaluation of Cost-effectiveness of the new immunosuppressive regimen, and comparison to the current standard of care
time frame: 24 months
description: Cost-effectiveness of the immunosuppressive regimen will be evaluated using state-of-the-art health-economic techniques; costs and effectiveness of immunosuppressive therapy will be derived from the study
arm group label: group 1
arm group type: Active Comparator
description: standard tacrolimus with mycophenolate mofetil
arm group label: group 2
arm group type: Experimental
description: low dose tacrolimus with everolimus
intervention type: Drug
intervention name: low dose tacrolimus in combination with everolimus
description: a low exposure Tacrolimus once-daily (Envarsus®) regimen in combination with Everolimus will be evaluated in elderly transplant recipients
arm group label: group 2
intervention type: Drug
intervention name: standard dose tacrolimus with mycophenolate mofetil
description: A standard Tacrolimus once-daily (Envarsus) regimen in combination with Everolimus will be evaluated in elderly transplant recipients
arm group label: group 1
criteria: 
gender: All
minimum age: 65 Years
maximum age: 99 Years
healthy volunteers: No
last name: Dennis Hesselink, MD, PhD
role: Principal Investigator
affiliation: EMC
last name: Frederike Bemelman, Md, PhD
role: Principal Investigator
affiliation: AIDS Malignancy Consortium
last name: Stefan Berger, Md, PhD
role: Study Chair
affiliation: UMCG
last name: Jan-Stephan Sanders, MD, PhD
role: Study Director
affiliation: UMCG
last name: Azam Nurmohamed, Md, PhD
role: Principal Investigator
affiliation: VUMC
last name: Aiko De Vries, MD, PhD
role: Principal Investigator
affiliation: LUMC
last name: Luuk Hilbrands, Md, PhD
role: Principal Investigator
affiliation: Radboud MC
last name: Arjan Van Zuilen, MD, PhD
role: Principal Investigator
affiliation: UMCU
last name: Dirk Kuypers, MD, PhD
role: Principal Investigator
affiliation: Leuven MC
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: University Medical Center Groningen
investigator full name: J.S.F. Sanders
investigator title: principal investigator, head of renal transplant program UMCG
mesh term: Mycophenolic Acid
mesh term: Everolimus
mesh term: Tacrolimus
sharing ipd: No