<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/NCT03841097</url>
  </required_header>
  <id_info>
    <org_study_id>832046</org_study_id>
    <nct_id>NCT03841097</nct_id>
  </id_info>
  <brief_title>Pulse Wave Velocity, Tacrolimus Time in Therapeutic Range and CV in African American Kidney Transplants</brief_title>
  <acronym>PTAAK</acronym>
  <official_title>A Phase IV, Prospective, Randomized, Open-label, Comparative Analysis, Single-center Study of Pulse Wave Velocity Evaluation, Tacrolimus TTR and Co-efficient of Tacrolimus Variation of African American Kidney Recipients Receiving Standard of Care Immediate Release Tacrolimus Capsules or Extended Release Tacrolimus Tablets</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Roy D. Bloom, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Veloxis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</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>
      The primary purpose of this study is to evaluate the pulse wave velocity and vascular&#xD;
      compliance measurements at the beginning and the end of the study while the participants are&#xD;
      taking either extended release tacrolimus tablets (known by brand name Envarsus XR®, and also&#xD;
      referred to as LCPT in this study) given once-daily each morning after transplantation or&#xD;
      immediate release tacrolimus capsules (also known by brand name Prograf® or abbreviation&#xD;
      IR-TAC in this study) that are administered twice-daily 12 hours apart after kidney&#xD;
      transplantation. Pulse wave velocity and vascular compliance measurements are two&#xD;
      non-invasive tests that are used to evaluate how well the blood vessels adapt to each&#xD;
      heartbeat. The secondary purpose is to look at the effectiveness and safety of LCPT given&#xD;
      once-daily compared to IR-TAC given twice-daily 12 hours apart after kidney transplantation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There are several medicines that are given to kidney transplant patients to prevent the&#xD;
      body's immune system from rejecting (not accepting) the transplanted kidney. Frequently, more&#xD;
      than one medicine is used at the same time to prevent rejection after kidney transplant. Some&#xD;
      of the medicines currently used are IR-TAC, Mycophenolate mofetil (MMF), Mycophenolate sodium&#xD;
      (MPS), and corticosteroids. IR-TAC is currently approved by the Food and Drug Administration&#xD;
      (FDA) under the trade name of Prograf® or equivalent generic versions to prevent rejection in&#xD;
      kidney transplant recipients. IR-TAC is taken twice daily (12 hours apart), and the dose is&#xD;
      adjusted by the transplant provider to keep the level of tacrolimus in the blood from being&#xD;
      too low or too high.&#xD;
&#xD;
      LCPT is a tablet containing the same active ingredient that is in IR-TAC but LCPT has been&#xD;
      designed to release tacrolimus over a longer period of time so that it only has to be taken&#xD;
      once a day in the morning. The dose of it is also adjusted by the transplant provider to keep&#xD;
      the level of tacrolimus in the blood from being too low or too high. It has been approved by&#xD;
      the FDA for prevention of rejection in kidney transplant recipients in combination with other&#xD;
      medications to prevent rejection after kidney transplant.&#xD;
&#xD;
      In this study, the participants will be randomly assigned by chance (like flipping a coin) to&#xD;
      receive either IR-TAC or LCPT from the time of transplant-on. Approximately half (30) of the&#xD;
      study participants will be given IR-TAC and half will be given LCPT. Both the study&#xD;
      participants and the transplant providers will know which medication that the participants&#xD;
      are receiving. The participants will remain in the study for up to 12 months during which&#xD;
      time they will be seen for monthly clinic visits, and complete labs per the standard of care.&#xD;
&#xD;
      Additionally, the study investigators will take an additional blood sample to further find&#xD;
      out how the body absorbs and breaks down the medication tacrolimus. Participants will also&#xD;
      undergo non-invasive pulse wave velocity and vascular compliance measurements within 3 days&#xD;
      of post transplant, then 1 month and 12 months after transplant. Pulse wave velocity and&#xD;
      vascular compliance measurements are two non-invasive tests that are used to evaluate how&#xD;
      well the blood vessels adapt to each heartbeat. All participants will also be taking either&#xD;
      Mycophenolate mofetil (MMF) or Mycophenolate sodium (MPS) and corticosteroids to prevent&#xD;
      rejection. These procedures will help the investigators to look at the effectiveness and&#xD;
      safety of LCPT compared to IR-TAC after kidney transplant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 11, 2019</start_date>
  <completion_date type="Anticipated">July 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2023</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>Assess Change in Pulse Wave Velocity</measure>
    <time_frame>baseline and months 12-24 post transplant</time_frame>
    <description>To assess the change in PWV measurements (m/sec) from baseline to 12-24 months after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assess Change in Vascular Compliance measurements</measure>
    <time_frame>baseline and months 12-24 post transplant</time_frame>
    <description>To assess the change in vascular compliance using central blood pressure (mmHg) from baseline to 12-24 months after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assess Change in Vascular Compliance</measure>
    <time_frame>baseline and months 12-24 post transplant</time_frame>
    <description>To assess the change in vascular compliance using Augmentation Index (ratio) from baseline to 12 -24 months after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assess Change in Pulse Wave Velocity measurements</measure>
    <time_frame>baseline and 1 month post transplant</time_frame>
    <description>To assess the change in PWV measurements (m/sec) from baseline to 1 month after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess Change in Vascular Compliance measurements</measure>
    <time_frame>baseline and 1 month post transplant</time_frame>
    <description>To assess the change in vascular compliance using central blood pressure (mmHg) from baseline to 1 month after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.&#xD;
Augmentation Index (ratio) measurements from baseline to 1 month after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess Change in Vascular Compliance</measure>
    <time_frame>baseline and 1 month post transplant</time_frame>
    <description>To assess the change in vascular compliance using Augmentation Index (ratio) from baseline to 1 month after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.&#xD;
Augmentation Index (ratio) measurements from baseline to 1 month after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare Percent of Kidney Recipients with Tacrolimus Time in Therapeutic Range</measure>
    <time_frame>1 year</time_frame>
    <description>To compare % of kidney recipient subjects with Tacrolimus time in therapeutic range (TTR) &lt; 60% or &lt; 75% by 12-24 months: (TTR will be defined as trough level between 7.5-12.5 ug/L between week 1 after transplant-month 1, 7.5-10.5ug/L between Months 2-3, 5.5-8.5 ug/L between months 4-12 after transplant, and 4.5-7.5ug/L 12 month onward) in patients on LCPT compared to those on IR-Tac.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the variability of Tacrolimus levels between LCPT and IR-Tac</measure>
    <time_frame>First 12-24 months</time_frame>
    <description>To compare the variability of Tacrolimus levels between LCPT and IR-Tac using coefficient of variation (CV); high Tacrolimus CV will be defined &gt; 40% during the first 12-24 months after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare steady-state mg/kg Tacrolimus dosing requirements</measure>
    <time_frame>At baseline</time_frame>
    <description>To compare steady-state mg/kg Tacrolimus dosing requirements to reach initial therapeutic troughs (defined as 8-12 ug/L) in kidney recipient subjects on LCPT compared to those on IR-Tac by CYP3A5*1 expressers vs. CYP3A5*1 non-expressers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare Tacrolimus-related medication adherence</measure>
    <time_frame>at months 1,2,3,6 and 12-24</time_frame>
    <description>To compare Tacrolimus-related medication adherence (measured by patient report of missed doses at transplant nephrology visits) in all kidney recipient subjects on LCPT compared to those on IR-Tac.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare mean systolic and arterial blood pressure</measure>
    <time_frame>at baseline and 12-24 months post-transplant</time_frame>
    <description>To compare mean systolic and arterial blood pressure in all kidney recipient subjects on LCPT compared to those on IR-Tac.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare anti-hypertensive medication use</measure>
    <time_frame>at baseline and 12-24 months post-transplant</time_frame>
    <description>To compare anti-hypertensive medication use in all kidney recipient subjects on LCPT compared to those on IR-Tac.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare mean diastolic and arterial blood pressure</measure>
    <time_frame>at baseline and 12-24 months post-transplant</time_frame>
    <description>To compare mean diastolic and arterial blood pressure in all kidney recipient subjects on LCPT compared to those on IR-Tac.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare estimated glomerular filtration rate (eGFR) measured by the Modification of Diet in Renal Disease (MDRD) formula</measure>
    <time_frame>At 6 months and 12-24 months post- transplant</time_frame>
    <description>To compare estimated glomerular filtration rate (eGFR) via Modification of Diet in Renal Disease (MDRD) 4 calculation in all kidney recipient subjects on LCPT compared to those on IR-Tac.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare hemoglobin A1C values</measure>
    <time_frame>Post- transplant at months 3, 6, and 12-24</time_frame>
    <description>To compare the occurrence of a new diagnosis pre-diabetes (as documented in the electronic health record) and hemoglobin A1C values in all non-diabetic kidney transplant subjects on LCPT compared to those on IR-Tac.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the incidence of development of donor specific antibodies</measure>
    <time_frame>At months 1, 3, 6 and 12-24 post- transplant</time_frame>
    <description>To compare the incidence of development of donor specific antibodies (DSA) in all kidney recipient subjects on LCPT compared to those on IR-Tac.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the incidence of development of BK virus</measure>
    <time_frame>At months 1, 3, 6, and 12-24 post- transplant</time_frame>
    <description>To compare the incidence of development of BK virus (defined as BKV &gt; 2.5 log copies/mL) in all kidney recipient subjects on LCPT compared to those on IR-Tac.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the incidence of serious adverse events</measure>
    <time_frame>At months 6 and 12-24 post- transplant</time_frame>
    <description>To compare the incidence of serious adverse events (SAEs) (including infections resulting in hospitalization, development of biopsy proven cellular and antibody mediated rejection by Banff criteria when biopsy performed for clinical indications, graft loss and patient death) in all kidney recipient subjects on LCPT compared to those on IR-Tac.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Kidney Transplant; Complications</condition>
  <arm_group>
    <arm_group_label>Extended Release Tacrolimus Tablets</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dosed once daily in the morning and started at a dose of 0.14 mg/kg/day by the first day after kidney transplant (post-operative day 1). This medication will be given with rabbit antithymocyte globulin (rATG) induction, oral mycophenolate mofetil (MMF) and oral steroids to help prevent rejection. These medications will be ordered per standard of care both inpatient and outpatient.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Immediate Release Tacrolimus Capsules</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dosed twice daily 12 hours apart and started at a dose of 0.1mg/kg/day by the first day after kidney transplant (post-operative day 1). This medication will be given with rabbit antithymocyte globulin (rATG) induction, oral mycophenolate mofetil (MMF) and oral steroids to help prevent rejection. These medications will be ordered per standard of care both inpatient and outpatient.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Extended Release Tacrolimus Tablets</intervention_name>
    <description>The primary objective is to assess the change in pulse wave velocity (PWV) and vascular compliance measurements from baseline to 12-24 months after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.</description>
    <arm_group_label>Extended Release Tacrolimus Tablets</arm_group_label>
    <other_name>LCPT</other_name>
    <other_name>Envarsus XR®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Immediate Release Tacrolimus Capsule</intervention_name>
    <description>The primary objective is to assess the change in pulse wave velocity (PWV) and vascular compliance measurements from baseline to 12-24 months after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.</description>
    <arm_group_label>Immediate Release Tacrolimus Capsules</arm_group_label>
    <other_name>IR-TAC</other_name>
    <other_name>Prograf®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects who self-report their race/ethnicity as Black-non-Hispanic only (which may&#xD;
             include self-reported African ancestry as African-American, Afro-Caribbean or African)&#xD;
&#xD;
          -  Subjects receiving a first or second deceased donor or living donor kidney transplant&#xD;
             at the Hospital of the University of Pennsylvania&#xD;
&#xD;
          -  Subjects whose body mass index (BMI) ≥19&#xD;
&#xD;
          -  Subjects who are sero-positive for Hepatitis B or C positive may also be enrolled.&#xD;
&#xD;
          -  Subjects whose concurrent immunosuppression at the time of transplant will be (generic&#xD;
             or brand formulation) Mycophenolate mofetil (MMF, CellCept) or mycophenolic sodium&#xD;
             (MPS, Myfortic®), either a standard prenisone taper or an early withdrawal protocol,&#xD;
             and induction with rabbit-antithymocyte globulin (Thymoglobulin®).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who are greater than 75 years old&#xD;
&#xD;
          -  Known hypersensitivity to Tacrolimus and hydrogenated castor oil&#xD;
&#xD;
          -  Subjects who are not self-described as being of Black African descent and living in&#xD;
             the United States&#xD;
&#xD;
          -  Subjects who self-report their race/ethnicity as Black-Hispanic or Multiracial&#xD;
&#xD;
          -  Subjects who are recipients of organ transplants other than kidney&#xD;
&#xD;
          -  Subjects who are recipients of third time or more kidney transplants&#xD;
&#xD;
          -  Subjects who are HIV positive at the time of pre-transplant screening&#xD;
&#xD;
          -  Subjects with recurrent focal segmental glomerulosclerosis (FSGS)&#xD;
&#xD;
          -  Subjects with any severe medical condition (including infection or severe liver&#xD;
             disease) requiring acute or chronic treatment that in the investigator's opinion would&#xD;
             interfere with study participation&#xD;
&#xD;
          -  Subjects with WBC ≤ 2000/mm3 or ANC ≤ 1500 mm3 with PLT ≤ 75,000/mm3 or HGB &lt; 8 g/dL&#xD;
&#xD;
          -  Subjects with mental or physical conditions or known non-adherence (defined as&#xD;
             documentation in the patient chart of multiple missed visits and/or medication doses)&#xD;
             which in the investigator's opinion would interfere with the objectives of the study&#xD;
&#xD;
          -  Subjects who have been exposed to investigational therapy within 30 days prior to&#xD;
             enrollment or five half-lives of the investigational product (whichever is greater).&#xD;
&#xD;
          -  Subjects with severe diabetic gastroparesis or other severe GI disturbances that could&#xD;
             interfere with Tacrolimus absorption&#xD;
&#xD;
          -  Subjects who have underwent gastric bypass at any time pre transplant.&#xD;
&#xD;
          -  Pregnant or nursing (lactating) women subjects, where pregnancy is defined as a state&#xD;
             of female after conception and until the termination of gestation, confirmed by a&#xD;
             positive hCG laboratory test (&gt; 5 mIU/ml).&#xD;
&#xD;
          -  Women subjects of child-bearing potential, defined as all women physiologically&#xD;
             capable of becoming pregnant who are unwilling to use a double-barrier method of&#xD;
             contraception, UNLESS they are&#xD;
&#xD;
          -  Women whose career, lifestyle, or sexual orientation preclude intercourse with a male&#xD;
             partner&#xD;
&#xD;
          -  Women whose partners have been sterilized by vasectomy or other means&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Roy D Bloom, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jennifer Trofe-Clark, Pharm D</last_name>
    <phone>215-614-4274</phone>
    <email>Jennifer.Trofe-Clark@uphs.upenn.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hospital of the University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jennifer Trofe-Clark, Pharm D</last_name>
      <phone>215-614-4274</phone>
      <email>jennifer.trofe-clark@uphs.upenn.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>February 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>April 12, 2023</last_update_submitted>
  <last_update_submitted_qc>April 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Pennsylvania</investigator_affiliation>
    <investigator_full_name>Roy D. Bloom, MD</investigator_full_name>
    <investigator_title>Principal Investigator, Professor of Medicine, and Medical Director of the Penn Kidney Transplant Program</investigator_title>
  </responsible_party>
  <keyword>Renal</keyword>
  <keyword>Transplant</keyword>
  <keyword>Pulse wave velocity</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tacrolimus</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/NCT03841097
org study id: 832046
nct id: NCT03841097
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The primary purpose of this study is to evaluate the pulse wave velocity and vascular
      compliance measurements at the beginning and the end of the study while the participants are
      taking either extended release tacrolimus tablets (known by brand name Envarsus XR®, and also
      referred to as LCPT in this study) given once-daily each morning after transplantation or
      immediate release tacrolimus capsules (also known by brand name Prograf® or abbreviation
      IR-TAC in this study) that are administered twice-daily 12 hours apart after kidney
      transplantation. Pulse wave velocity and vascular compliance measurements are two
      non-invasive tests that are used to evaluate how well the blood vessels adapt to each
      heartbeat. The secondary purpose is to look at the effectiveness and safety of LCPT given
      once-daily compared to IR-TAC given twice-daily 12 hours apart after kidney transplantation.
There are several medicines that are given to kidney transplant patients to prevent the
      body's immune system from rejecting (not accepting) the transplanted kidney. Frequently, more
      than one medicine is used at the same time to prevent rejection after kidney transplant. Some
      of the medicines currently used are IR-TAC, Mycophenolate mofetil (MMF), Mycophenolate sodium
      (MPS), and corticosteroids. IR-TAC is currently approved by the Food and Drug Administration
      (FDA) under the trade name of Prograf® or equivalent generic versions to prevent rejection in
      kidney transplant recipients. IR-TAC is taken twice daily (12 hours apart), and the dose is
      adjusted by the transplant provider to keep the level of tacrolimus in the blood from being
      too low or too high.

      LCPT is a tablet containing the same active ingredient that is in IR-TAC but LCPT has been
      designed to release tacrolimus over a longer period of time so that it only has to be taken
      once a day in the morning. The dose of it is also adjusted by the transplant provider to keep
      the level of tacrolimus in the blood from being too low or too high. It has been approved by
      the FDA for prevention of rejection in kidney transplant recipients in combination with other
      medications to prevent rejection after kidney transplant.

      In this study, the participants will be randomly assigned by chance (like flipping a coin) to
      receive either IR-TAC or LCPT from the time of transplant-on. Approximately half (30) of the
      study participants will be given IR-TAC and half will be given LCPT. Both the study
      participants and the transplant providers will know which medication that the participants
      are receiving. The participants will remain in the study for up to 12 months during which
      time they will be seen for monthly clinic visits, and complete labs per the standard of care.

      Additionally, the study investigators will take an additional blood sample to further find
      out how the body absorbs and breaks down the medication tacrolimus. Participants will also
      undergo non-invasive pulse wave velocity and vascular compliance measurements within 3 days
      of post transplant, then 1 month and 12 months after transplant. Pulse wave velocity and
      vascular compliance measurements are two non-invasive tests that are used to evaluate how
      well the blood vessels adapt to each heartbeat. All participants will also be taking either
      Mycophenolate mofetil (MMF) or Mycophenolate sodium (MPS) and corticosteroids to prevent
      rejection. These procedures will help the investigators to look at the effectiveness and
      safety of LCPT compared to IR-TAC after kidney transplant.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Assess Change in Pulse Wave Velocity
time frame: baseline and months 12-24 post transplant
description: To assess the change in PWV measurements (m/sec) from baseline to 12-24 months after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.
measure: Assess Change in Vascular Compliance measurements
time frame: baseline and months 12-24 post transplant
description: To assess the change in vascular compliance using central blood pressure (mmHg) from baseline to 12-24 months after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.
measure: Assess Change in Vascular Compliance
time frame: baseline and months 12-24 post transplant
description: To assess the change in vascular compliance using Augmentation Index (ratio) from baseline to 12 -24 months after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.
measure: Assess Change in Pulse Wave Velocity measurements
time frame: baseline and 1 month post transplant
description: To assess the change in PWV measurements (m/sec) from baseline to 1 month after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.
measure: Assess Change in Vascular Compliance measurements
time frame: baseline and 1 month post transplant
description: To assess the change in vascular compliance using central blood pressure (mmHg) from baseline to 1 month after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.
Augmentation Index (ratio) measurements from baseline to 1 month after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.
measure: Assess Change in Vascular Compliance
time frame: baseline and 1 month post transplant
description: To assess the change in vascular compliance using Augmentation Index (ratio) from baseline to 1 month after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.
Augmentation Index (ratio) measurements from baseline to 1 month after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.
measure: Compare Percent of Kidney Recipients with Tacrolimus Time in Therapeutic Range
time frame: 1 year
description: To compare % of kidney recipient subjects with Tacrolimus time in therapeutic range (TTR) < 60% or < 75% by 12-24 months: (TTR will be defined as trough level between 7.5-12.5 ug/L between week 1 after transplant-month 1, 7.5-10.5ug/L between Months 2-3, 5.5-8.5 ug/L between months 4-12 after transplant, and 4.5-7.5ug/L 12 month onward) in patients on LCPT compared to those on IR-Tac.
measure: Compare the variability of Tacrolimus levels between LCPT and IR-Tac
time frame: First 12-24 months
description: To compare the variability of Tacrolimus levels between LCPT and IR-Tac using coefficient of variation (CV); high Tacrolimus CV will be defined > 40% during the first 12-24 months after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.
measure: Compare steady-state mg/kg Tacrolimus dosing requirements
time frame: At baseline
description: To compare steady-state mg/kg Tacrolimus dosing requirements to reach initial therapeutic troughs (defined as 8-12 ug/L) in kidney recipient subjects on LCPT compared to those on IR-Tac by CYP3A5*1 expressers vs. CYP3A5*1 non-expressers.
measure: Compare Tacrolimus-related medication adherence
time frame: at months 1,2,3,6 and 12-24
description: To compare Tacrolimus-related medication adherence (measured by patient report of missed doses at transplant nephrology visits) in all kidney recipient subjects on LCPT compared to those on IR-Tac.
measure: Compare mean systolic and arterial blood pressure
time frame: at baseline and 12-24 months post-transplant
description: To compare mean systolic and arterial blood pressure in all kidney recipient subjects on LCPT compared to those on IR-Tac.
measure: Compare anti-hypertensive medication use
time frame: at baseline and 12-24 months post-transplant
description: To compare anti-hypertensive medication use in all kidney recipient subjects on LCPT compared to those on IR-Tac.
measure: Compare mean diastolic and arterial blood pressure
time frame: at baseline and 12-24 months post-transplant
description: To compare mean diastolic and arterial blood pressure in all kidney recipient subjects on LCPT compared to those on IR-Tac.
measure: Compare estimated glomerular filtration rate (eGFR) measured by the Modification of Diet in Renal Disease (MDRD) formula
time frame: At 6 months and 12-24 months post- transplant
description: To compare estimated glomerular filtration rate (eGFR) via Modification of Diet in Renal Disease (MDRD) 4 calculation in all kidney recipient subjects on LCPT compared to those on IR-Tac.
measure: Compare hemoglobin A1C values
time frame: Post- transplant at months 3, 6, and 12-24
description: To compare the occurrence of a new diagnosis pre-diabetes (as documented in the electronic health record) and hemoglobin A1C values in all non-diabetic kidney transplant subjects on LCPT compared to those on IR-Tac.
measure: Compare the incidence of development of donor specific antibodies
time frame: At months 1, 3, 6 and 12-24 post- transplant
description: To compare the incidence of development of donor specific antibodies (DSA) in all kidney recipient subjects on LCPT compared to those on IR-Tac.
measure: Compare the incidence of development of BK virus
time frame: At months 1, 3, 6, and 12-24 post- transplant
description: To compare the incidence of development of BK virus (defined as BKV > 2.5 log copies/mL) in all kidney recipient subjects on LCPT compared to those on IR-Tac.
measure: Compare the incidence of serious adverse events
time frame: At months 6 and 12-24 post- transplant
description: To compare the incidence of serious adverse events (SAEs) (including infections resulting in hospitalization, development of biopsy proven cellular and antibody mediated rejection by Banff criteria when biopsy performed for clinical indications, graft loss and patient death) in all kidney recipient subjects on LCPT compared to those on IR-Tac.
arm group label: Extended Release Tacrolimus Tablets
arm group type: Active Comparator
description: Dosed once daily in the morning and started at a dose of 0.14 mg/kg/day by the first day after kidney transplant (post-operative day 1). This medication will be given with rabbit antithymocyte globulin (rATG) induction, oral mycophenolate mofetil (MMF) and oral steroids to help prevent rejection. These medications will be ordered per standard of care both inpatient and outpatient.
arm group label: Immediate Release Tacrolimus Capsules
arm group type: Active Comparator
description: Dosed twice daily 12 hours apart and started at a dose of 0.1mg/kg/day by the first day after kidney transplant (post-operative day 1). This medication will be given with rabbit antithymocyte globulin (rATG) induction, oral mycophenolate mofetil (MMF) and oral steroids to help prevent rejection. These medications will be ordered per standard of care both inpatient and outpatient.
intervention type: Drug
intervention name: Extended Release Tacrolimus Tablets
description: The primary objective is to assess the change in pulse wave velocity (PWV) and vascular compliance measurements from baseline to 12-24 months after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.
arm group label: Extended Release Tacrolimus Tablets
other name: LCPT
other name: Envarsus XR®
intervention type: Drug
intervention name: Immediate Release Tacrolimus Capsule
description: The primary objective is to assess the change in pulse wave velocity (PWV) and vascular compliance measurements from baseline to 12-24 months after transplant in kidney recipient subjects on LCPT compared to those on IR-Tac.
arm group label: Immediate Release Tacrolimus Capsules
other name: IR-TAC
other name: Prograf®
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Roy D Bloom, MD
role: Principal Investigator
affiliation: University of Pennsylvania
last name: Jennifer Trofe-Clark, Pharm D
phone: 215-614-4274
email: Jennifer.Trofe-Clark@uphs.upenn.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Pennsylvania
investigator full name: Roy D. Bloom, MD
investigator title: Principal Investigator, Professor of Medicine, and Medical Director of the Penn Kidney Transplant Program
mesh term: Tacrolimus