<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/NCT03828058</url>
  </required_header>
  <id_info>
    <org_study_id>18-05876-FB</org_study_id>
    <nct_id>NCT03828058</nct_id>
  </id_info>
  <brief_title>Envarsus XL Immunosuppression Following Liver Transplantation</brief_title>
  <official_title>A 12 Month Single-center, Open Label, Randomized, Comparative Study to Evaluate Envarsus XL Steroid-free Rabbit Anti-thymocyte Globulin Induction on Renal Function and Health-related Quality of Life Following Liver Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Methodist Healthcare</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Methodist Healthcare</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The standard immunosuppressive regimen for liver transplantation includes twice daily&#xD;
      tacrolimus (Prograf). In other transplantation models, there are potential benefits to&#xD;
      extended release formulations as lower peak concentrations are thought to have lower rates of&#xD;
      nephrotoxicity. Additionally, compliance with once daily medications is felt to be easier&#xD;
      than twice daily medications. Our aim is to look at our prospective liver transplant group&#xD;
      and see if once daily tacrolimus (Envarsus XR) results in improved renal function as well as&#xD;
      improved health care quality of life.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 1, 2019</start_date>
  <completion_date type="Actual">December 31, 2020</completion_date>
  <primary_completion_date type="Actual">December 31, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>The study will be a prospective, randomized, open label study comparing Envarsus XR with twice daily prograf.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in estimated glomerular filtration rate (eGFR) over the first year after liver transplant</measure>
    <time_frame>3, 6, and 12 months post-transplant</time_frame>
    <description>We will be assessing differences in renal function based on calculated eGFR by MDRD6 equation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quality of Life Assessment</measure>
    <time_frame>3, 6, and 12 months post-transplant</time_frame>
    <description>We will be using the RAND Short Form 36 (SF36) healthcare survey to assess patient reported quality of life across a broad spectrum ranging from physical health and function to emotional well being. Each sub scale score ranges from 0 (worse) to 100 (best).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">110</enrollment>
  <condition>Recipients of Liver Transplant</condition>
  <arm_group>
    <arm_group_label>Envarsus XR</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Envarsus XR orally administered Daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Prograf</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Prograf PO administered twice daily Generic Name: tacrolimus&#xD;
Dosage of prograf will be determined by trough levels and adjusted accordingly</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Envarsus XR</intervention_name>
    <description>Envarsus XR to be administered orally, once a day. Dosage will be adjusted as determined by trough blood levels.</description>
    <arm_group_label>Envarsus XR</arm_group_label>
    <other_name>ENVARSUS XR 0.75Mg Extended-Release Tablet</other_name>
    <other_name>ENVARSUS XR 1Mg Extended-Release Tablet</other_name>
    <other_name>ENVARSUS XR 4Mg Extended-Release Tablet</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prograf</intervention_name>
    <description>Prograf 2 mg BID to be administered orally, twice a day. Dosage will be adjusted as determined by trough blood levels.</description>
    <arm_group_label>Prograf</arm_group_label>
    <other_name>Tacrolimus</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provision of signed and dated informed consent form&#xD;
&#xD;
          2. Stated willingness to comply with all study procedures and availability for the&#xD;
             duration of the study&#xD;
&#xD;
          3. Male or female, aged 18 years or older&#xD;
&#xD;
          4. Recipients of a first-time liver transplant&#xD;
&#xD;
          5. Serum Creatinine level less than 2.0 on Post-Operative Day 3-7&#xD;
&#xD;
          6. Ability to take oral medication and be willing to adhere to the assigned&#xD;
             immunosuppression regimen&#xD;
&#xD;
          7. Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study&#xD;
             duration&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any prior use of tacrolimus or cyclosporine&#xD;
&#xD;
          2. Recipients of prior organ transplant&#xD;
&#xD;
          3. Need for hemodialysis in the week preceding or following liver transplantation&#xD;
&#xD;
          4. Recipients of living donor liver or split deceased donor liver allografts&#xD;
&#xD;
          5. Recipients of combined liver/kidney transplants&#xD;
&#xD;
          6. Pregnancy or lactation&#xD;
&#xD;
          7. Recipients of ABO incompatible liver allografts&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James Eason, MD</last_name>
    <role>Study Director</role>
    <affiliation>The University of Tennessee Health Science Center, Department of Transplant</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Methodist Healthcare, University Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Kadam P, Bhalerao S. Sample size calculation. Int J Ayurveda Res. 2010 Jan;1(1):55-7. doi: 10.4103/0974-7788.59946. No abstract available.</citation>
    <PMID>20532100</PMID>
  </reference>
  <results_reference>
    <citation>Abdelmalek MF, Humar A, Stickel F, Andreone P, Pascher A, Barroso E, Neff GW, Ranjan D, Toselli LT, Gane EJ, Scarola J, Alberts RG, Maller ES, Lo CM; Sirolimus Liver Conversion Trial Study Group. Sirolimus conversion regimen versus continued calcineurin inhibitors in liver allograft recipients: a randomized trial. Am J Transplant. 2012 Mar;12(3):694-705. doi: 10.1111/j.1600-6143.2011.03919.x. Epub 2012 Jan 10.</citation>
    <PMID>22233522</PMID>
  </results_reference>
  <results_reference>
    <citation>Backman L, Nicar M, Levy M, Distant D, Eisenstein C, Renard T, Goldstein R, Husberg B, Gonwa TA, Klintmalm G. FK506 trough levels in whole blood and plasma in liver transplant recipients. Correlation with clinical events and side effects. Transplantation. 1994 Feb 27;57(4):519-25.</citation>
    <PMID>7509516</PMID>
  </results_reference>
  <results_reference>
    <citation>Kong Y, Wang D, Shang Y, Liang W, Ling X, Guo Z, He X. Calcineurin-inhibitor minimization in liver transplant patients with calcineurin-inhibitor-related renal dysfunction: a meta-analysis. PLoS One. 2011;6(9):e24387. doi: 10.1371/journal.pone.0024387. Epub 2011 Sep 9.</citation>
    <PMID>21931704</PMID>
  </results_reference>
  <results_reference>
    <citation>Langone A, Steinberg SM, Gedaly R, Chan LK, Shah T, Sethi KD, Nigro V, Morgan JC; STRATO Investigators. Switching STudy of Kidney TRansplant PAtients with Tremor to LCP-TacrO (STRATO): an open-label, multicenter, prospective phase 3b study. Clin Transplant. 2015 Sep;29(9):796-805. doi: 10.1111/ctr.12581. Epub 2015 Aug 6.</citation>
    <PMID>26113208</PMID>
  </results_reference>
  <results_reference>
    <citation>Yoo MC, Vanatta JM, Modanlou KA, Campos L, Nezakatgoo N, Nair S, Eason JD. Steroid-free Liver Transplantation Using Rabbit Antithymocyte Globulin Induction in 500 Consecutive Patients. Transplantation. 2015 Jun;99(6):1231-5. doi: 10.1097/TP.0000000000000477.</citation>
    <PMID>25539464</PMID>
  </results_reference>
  <results_reference>
    <citation>Garnock-Jones KP. Tacrolimus prolonged release (Envarsus(R)): a review of its use in kidney and liver transplant recipients. Drugs. 2015 Feb;75(3):309-20. doi: 10.1007/s40265-015-0349-2.</citation>
    <PMID>25613762</PMID>
  </results_reference>
  <results_reference>
    <citation>Niel OR, Berthoux F, Albano L, Dahan P, Aoudia R, Gugenheim J, Cassuto E. Long-term glomerular filtration rate in liver allograft recipients according to the type of calcineurin inhibitors. Transplant Proc. 2009 Oct;41(8):3329-32. doi: 10.1016/j.transproceed.2009.09.034.</citation>
    <PMID>19857743</PMID>
  </results_reference>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>December 11, 2018</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>January 11, 2021</last_update_submitted>
  <last_update_submitted_qc>January 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 12, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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/NCT03828058
org study id: 18-05876-FB
nct id: NCT03828058
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The standard immunosuppressive regimen for liver transplantation includes twice daily
      tacrolimus (Prograf). In other transplantation models, there are potential benefits to
      extended release formulations as lower peak concentrations are thought to have lower rates of
      nephrotoxicity. Additionally, compliance with once daily medications is felt to be easier
      than twice daily medications. Our aim is to look at our prospective liver transplant group
      and see if once daily tacrolimus (Envarsus XR) results in improved renal function as well as
      improved health care quality of life.
allocation: Randomized
intervention model: Single Group Assignment
intervention model description: The study will be a prospective, randomized, open label study comparing Envarsus XR with twice daily prograf.
primary purpose: Treatment
masking: None (Open Label)
measure: Change in estimated glomerular filtration rate (eGFR) over the first year after liver transplant
time frame: 3, 6, and 12 months post-transplant
description: We will be assessing differences in renal function based on calculated eGFR by MDRD6 equation.
measure: Quality of Life Assessment
time frame: 3, 6, and 12 months post-transplant
description: We will be using the RAND Short Form 36 (SF36) healthcare survey to assess patient reported quality of life across a broad spectrum ranging from physical health and function to emotional well being. Each sub scale score ranges from 0 (worse) to 100 (best).
arm group label: Envarsus XR
arm group type: Experimental
description: Envarsus XR orally administered Daily
arm group label: Prograf
arm group type: Active Comparator
description: Prograf PO administered twice daily Generic Name: tacrolimus
Dosage of prograf will be determined by trough levels and adjusted accordingly
intervention type: Drug
intervention name: Envarsus XR
description: Envarsus XR to be administered orally, once a day. Dosage will be adjusted as determined by trough blood levels.
arm group label: Envarsus XR
other name: ENVARSUS XR 0.75Mg Extended-Release Tablet
other name: ENVARSUS XR 1Mg Extended-Release Tablet
other name: ENVARSUS XR 4Mg Extended-Release Tablet
intervention type: Drug
intervention name: Prograf
description: Prograf 2 mg BID to be administered orally, twice a day. Dosage will be adjusted as determined by trough blood levels.
arm group label: Prograf
other name: Tacrolimus
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: James Eason, MD
role: Study Director
affiliation: The University of Tennessee Health Science Center, Department of Transplant
facility: 
country: United States
citation: Kadam P, Bhalerao S. Sample size calculation. Int J Ayurveda Res. 2010 Jan;1(1):55-7. doi: 10.4103/0974-7788.59946. No abstract available.
PMID: 20532100
citation: Abdelmalek MF, Humar A, Stickel F, Andreone P, Pascher A, Barroso E, Neff GW, Ranjan D, Toselli LT, Gane EJ, Scarola J, Alberts RG, Maller ES, Lo CM; Sirolimus Liver Conversion Trial Study Group. Sirolimus conversion regimen versus continued calcineurin inhibitors in liver allograft recipients: a randomized trial. Am J Transplant. 2012 Mar;12(3):694-705. doi: 10.1111/j.1600-6143.2011.03919.x. Epub 2012 Jan 10.
PMID: 22233522
citation: Backman L, Nicar M, Levy M, Distant D, Eisenstein C, Renard T, Goldstein R, Husberg B, Gonwa TA, Klintmalm G. FK506 trough levels in whole blood and plasma in liver transplant recipients. Correlation with clinical events and side effects. Transplantation. 1994 Feb 27;57(4):519-25.
PMID: 7509516
citation: Kong Y, Wang D, Shang Y, Liang W, Ling X, Guo Z, He X. Calcineurin-inhibitor minimization in liver transplant patients with calcineurin-inhibitor-related renal dysfunction: a meta-analysis. PLoS One. 2011;6(9):e24387. doi: 10.1371/journal.pone.0024387. Epub 2011 Sep 9.
PMID: 21931704
citation: Langone A, Steinberg SM, Gedaly R, Chan LK, Shah T, Sethi KD, Nigro V, Morgan JC; STRATO Investigators. Switching STudy of Kidney TRansplant PAtients with Tremor to LCP-TacrO (STRATO): an open-label, multicenter, prospective phase 3b study. Clin Transplant. 2015 Sep;29(9):796-805. doi: 10.1111/ctr.12581. Epub 2015 Aug 6.
PMID: 26113208
citation: Yoo MC, Vanatta JM, Modanlou KA, Campos L, Nezakatgoo N, Nair S, Eason JD. Steroid-free Liver Transplantation Using Rabbit Antithymocyte Globulin Induction in 500 Consecutive Patients. Transplantation. 2015 Jun;99(6):1231-5. doi: 10.1097/TP.0000000000000477.
PMID: 25539464
citation: Garnock-Jones KP. Tacrolimus prolonged release (Envarsus(R)): a review of its use in kidney and liver transplant recipients. Drugs. 2015 Feb;75(3):309-20. doi: 10.1007/s40265-015-0349-2.
PMID: 25613762
citation: Niel OR, Berthoux F, Albano L, Dahan P, Aoudia R, Gugenheim J, Cassuto E. Long-term glomerular filtration rate in liver allograft recipients according to the type of calcineurin inhibitors. Transplant Proc. 2009 Oct;41(8):3329-32. doi: 10.1016/j.transproceed.2009.09.034.
PMID: 19857743
responsible party type: Sponsor
mesh term: Tacrolimus
sharing ipd: No