xml: <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/NCT06013865</url>
    </required_header>
    <id_info>
      <org_study_id>NEPH-008-22F</org_study_id>
      <secondary_id>CSR&amp;D</secondary_id>
      <nct_id>NCT06013865</nct_id>
    </id_info>
    <brief_title>Empagliflozin Treatment in Kidney Transplant Recipients</brief_title>
    <acronym>SEKTR</acronym>
    <official_title>An Exploratory Investigation of the Safety of Empagliflozin in Kidney Transplant Recipients (SEKTR)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>VA Office of Research and Development</agency>
        <agency_class>U.S. Fed</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Iowa City VA Health Care System</agency>
        <agency_class>U.S. Fed</agency_class>
      </collaborator>
      <collaborator>
        <agency>VA Pittsburgh Healthcare System</agency>
        <agency_class>U.S. Fed</agency_class>
      </collaborator>
      <collaborator>
        <agency>Nashville VA Medical Center</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>VA Office of Research and Development</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>
        Kidney transplantation improves the health and quality of life for those Veterans with end&#xD;
        stage kidney disease (ESKD). While early patient and graft survival are excellent, long-term&#xD;
        outcomes continue to be challenging. Patient death with existing kidney graft function occurs&#xD;
        in about half of all recipients over time. This is primarily due to the development of&#xD;
        cardiovascular disease in a patient population with multiple preexisting cardiac disease risk&#xD;
        factors. There has been little progress in improving outcomes in this area for over two&#xD;
        decades. Recent studies in chronic kidney disease (CKD) patients using SGLT2 inhibitors&#xD;
        (SGLT2i), regardless of the presence of type 2 diabetes mellitus (T2DM), results in both&#xD;
        kidney protective and cardiac protective impacts and improved patient outcomes. However,&#xD;
        kidney transplant recipients (KTRs) were excluded from these clinical trials due to concerns&#xD;
        that these agents promote infection, diminish graft function, and may alter immunosuppressive&#xD;
        drug levels that are the mainstay of patient's transplant therapy. There are limited&#xD;
        published data of SGLT2i treatment of selected KTRs.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Background: Kidney transplantation improves the health and quality of life for those veterans&#xD;
        with end stage kidney disease (ESKD). While early patient and graft survival are excellent,&#xD;
        long-term outcomes continue to be challenging. Patient death with existing kidney graft&#xD;
        function occurs in about half of all recipients over time. This is primarily due to the&#xD;
        development of cardiovascular disease in a patient population with multiple preexisting&#xD;
        cardiac disease risk factors. There has been little progress in improving outcomes in this&#xD;
        area for over two decades. Recent studies in chronic kidney disease (CKD) patients using&#xD;
        SGLT2 inhibitors (SGLT2i), regardless of the presence of type 2 diabetes mellitus (T2DM),&#xD;
        results in both kidney protective and cardiac protective impacts and improved patient&#xD;
        outcomes. However, kidney transplant recipients (KTRs) were excluded from these clinical&#xD;
        trials due to concerns that these agents promote infection, diminish graft function, and may&#xD;
        alter immunosuppressive drug levels that are the mainstay of patient's transplant therapy.&#xD;
        There are limited published data of SGLT2i treatment of selected KTRs.&#xD;
  &#xD;
        Objective: The goal of this submission is to examine the safety and efficacy of SGLT2i&#xD;
        therapy in Veterans with KTRs and T2DM. The hypothesis is treatment with SGLT2i will lead to&#xD;
        improvements in graft and cardiovascular outcomes in patients with T2DM, with acceptable side&#xD;
        effect profile.&#xD;
  &#xD;
        Methods: To test this hypothesis, the investigators will execute a multicenter clinical trial&#xD;
        at 4 VA medical centers, including 3 that serve as primary kidney transplant programs. The&#xD;
        multidisciplinary research team includes transplant medical and surgical expertise,&#xD;
        diabetology, and informatics and statistical support familiar with VA data systems. In open&#xD;
        label fashion, the investigators will treat eligible KTRs and comprehensively assess adverse&#xD;
        and serious adverse event data, as well as assess any untoward impacts on graft function and&#xD;
        diabetes management. Secondly, the investigators will utilize VA data from the VINCI&#xD;
        corporate data warehouse to develop a control cohort of Veterans with KTRs and T2DM, not&#xD;
        treated with SGLT2i. The investigators will utilize propensity score matching to reduce bias&#xD;
        that may occur in observational studies. With this strategy, the investigators will further&#xD;
        address the potential beneficial impact of SGLT2i treatment on cardiovascular outcomes, as&#xD;
        well as kidney disease progression in the transplanted kidney. The investigators will also&#xD;
        analyze the cost impact of using this agent in this patient population, in terms of&#xD;
        hospitalizations, unanticipated procedures, and CKD management.&#xD;
  &#xD;
        Findings: These studies will provide new information to the transplant community for both&#xD;
        Veteran and non-Veteran alike, with a detailed assessment of safety and feasibility of this&#xD;
        agent class using a pragmatic approach to transplant care. These results will translate into&#xD;
        an opportunity to mitigate late graft loss in this patient population, and a potential&#xD;
        breakthrough in clinical care that to date has been unrecognized.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 1, 2024</start_date>
    <completion_date type="Anticipated">December 31, 2030</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2029</primary_completion_date>
    <phase>N/A</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>
      <intervention_model_description>Prospective Observational Cohort Study</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Discontinuation of Empagliflozin</measure>
      <time_frame>about 2 years</time_frame>
      <description>The incidence of therapeutic discontinuation of empagliflozin in the kidney transplant recipient from time of initiation.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Infection</measure>
      <time_frame>about 2 years</time_frame>
      <description>Defined as the cumulative incidence of study defined Grade 3 or higher infection of the urinary tract or perineum after initiation of treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hypoglycemia</measure>
      <time_frame>about 2 years</time_frame>
      <description>The cumulative incidence of grade 3 hypoglycemia</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Major cardiorenal events</measure>
      <time_frame>about 2 years</time_frame>
      <description>Time to first occurrence of the composite of major adverse cardiorenal events (MACER) as defined as all-cause mortality, stroke, non-fatal myocardial infarction, heart failure events including hospitalization for CHF or urgent CHF treatment, sustained (for at least 3 months) 40% decline in eGFR, or allograft failure as defined by chronic dialysis, re-transplantation, or persistent eGFR &lt;15mL/min/1.73m2)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Acute Graft Dysfunction</measure>
      <time_frame>about 2 years</time_frame>
      <description>The cumulative incidence of &gt;15% elevation in serum creatinine for more than 4 weeks from the baseline defined prior to treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Volume Depletion</measure>
      <time_frame>about 2 years</time_frame>
      <description>The cumulative incidence of grade 3 volume depletion.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Acute Cellular Rejection</measure>
      <time_frame>about 2 years</time_frame>
      <description>The cumulative incidence of acute rejection biopsy proven using 2017 criteria:&#xD;
  Type IA Moderate tubulitis and at least moderate interstitial inflammation t2i2 or t2i3 Type IB Severe tubulitis and at least moderate interstitial inflammation t3i2 or t3i3 Type IIA Mild to moderate intimal arteritis v1 Type IIB Severe intimal arteritis (&gt; 25% of the luminal area) v2 Type III Transmural' arteritis and/or fibrinoid necrosis v3 Borderline: no intimal arteritis is present, t&gt;0 and i1 or i2/i3 and t1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Amputation and foot ulceration</measure>
      <time_frame>About 2 years</time_frame>
      <description>The cumulative incidence of Grade 3 foot ulceration and/or need for amputation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proteinuria</measure>
      <time_frame>12 and 24 months</time_frame>
      <description>Spot Urine Protein/creatinine ratio</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Allograft Biopsy</measure>
      <time_frame>about 2 years</time_frame>
      <description>Time to incidence of a decline in eGFR sufficient to trigger a clinical decision for an allograft biopsy</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>MACER</measure>
      <time_frame>about 2 years</time_frame>
      <description>Time to first occurrence of individual component of the MACER secondary outcome</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Death</measure>
      <time_frame>about 2 years</time_frame>
      <description>Time to the occurrence of cardiovascular death</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Acute graft dysfunction</measure>
      <time_frame>About 2 years</time_frame>
      <description>Time to acute kidney injury as defined as a &gt;15% change in eGFR from baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Slope of kidney function</measure>
      <time_frame>over 2 years</time_frame>
      <description>Serum creatinine measured in mg/dL for all participants prior to treatment, at month 6, month 12 and month 24 of treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Glycemic Control</measure>
      <time_frame>over 2 years</time_frame>
      <description>Changes in Hemoglobin A1C over time of treatment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Body Weight</measure>
      <time_frame>over 2 years</time_frame>
      <description>Change in body weight over time of treatment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood Pressure</measure>
      <time_frame>over 2 years</time_frame>
      <description>Change in blood pressure measured in mmHg over the course of the study</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">264</enrollment>
    <condition>Kidney Transplant</condition>
    <condition>Type 2 Diabetes</condition>
    <arm_group>
      <arm_group_label>Empagliflozin</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Open Label, Empagliflozin 12.5 mg QD</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Empagliflozin</intervention_name>
      <description>SGLT2 Inhibitor</description>
      <arm_group_label>Empagliflozin</arm_group_label>
      <other_name>jardiance</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          INCLUSION CRITERIA&#xD;
  &#xD;
            1. Adult (&gt;18 years of age) male and female recipients (all races and ethnicities)&#xD;
  &#xD;
            2. Subject must be able to understand and provide consent&#xD;
  &#xD;
            3. Recipient of a primary or secondary kidney transplant at least 3 months or longer&#xD;
               since transplant&#xD;
  &#xD;
            4. Subject must have a diagnosis of Type 2 Diabetes Mellitus or post-transplant diabetes&#xD;
               mellitus (PTDM) 2DM or PTDM&#xD;
  &#xD;
            5. Subject must be able to travel to and from VAMC for care and monitoring&#xD;
  &#xD;
            6. Subject must have kidney function measured by CKD epi eGFR 30 mL/min/1.73m2 to &lt;&#xD;
               45ml/min/1.73m2 or CKD epi eGFR 45 mL/min/1.73m2 to 90ml/min/1.73m2 with urinary&#xD;
               albumin:creatinine ratio 200 mg/g (or protein:creatinine 300 mg/g).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          EXCLUSION CRITERIA&#xD;
  &#xD;
            1. Inability or unwillingness of a participant to give written informed consent or comply&#xD;
               with study protocol&#xD;
  &#xD;
            2. History of prior pancreas transplant&#xD;
  &#xD;
            3. CKD epi eGFR&lt; 30 mL/min/1.73m2 with 5mL/min/1.73m2 fall per year&#xD;
  &#xD;
            4. Uncontrolled type 2 diabetes mellitus with most recent A1C&gt;12%&#xD;
  &#xD;
            5. History of &gt;2 urinary tract infections per year or UTIs requiring admission in the&#xD;
               last year, or urosepsis in the last year.&#xD;
  &#xD;
            6. Use of SGLT2i within 90 days&#xD;
  &#xD;
            7. Documented allergy to SGLT2i&#xD;
  &#xD;
            8. History of Type I diabetes mellitus&#xD;
  &#xD;
            9. History of diabetic ketoacidosis&#xD;
  &#xD;
           10. Indwelling foley catheter or urinary diversion&#xD;
  &#xD;
           11. Acute rejection in the prior 3 months&#xD;
  &#xD;
           12. Acute MACE event within 3 months of the study&#xD;
  &#xD;
           13. Severe congestive heart failure (NYHA functional class III or higher)&#xD;
  &#xD;
           14. Active mucocutaneous mycotic infection of the groin or external genitalia.&#xD;
  &#xD;
           15. History of amputation due to peripheral vascular disease and/or diabetic foot ulcers&#xD;
               within prior year&#xD;
  &#xD;
           16. History of malignancy except non-melanoma skin cancer within 5 years of screening&#xD;
  &#xD;
           17. Known active current viral, fungal, mycobacterial, or other infections (including, but&#xD;
               not limited to tuberculosis and atypical mycobacterial disease)&#xD;
  &#xD;
           18. HIV infected subjects, including those who are well controlled on anti-retrovirals&#xD;
  &#xD;
           19. Positive Hep B PCR&#xD;
  &#xD;
           20. Hepatitis C virus antibody positive (HCVAb+) subjects who have failed to demonstrate&#xD;
               sustained viral remission for more than 12 weeks (after anti-viral treatment)&#xD;
  &#xD;
           21. Active pregnancy in a female transplant recipient&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>19 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Roslyn B Mannon, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Roslyn B Mannon, MD</last_name>
      <phone>(205) 999-7362</phone>
      <email>roslyn.mannon@va.gov</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Ramesh K Ramalingam</last_name>
      <phone>(402) 995-4873</phone>
      <email>Ramesh.Ramalingam@va.gov</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Iowa City VA Health Care System, Iowa City, IA</name>
        <address>
          <city>Iowa City</city>
          <state>Iowa</state>
          <zip>52246-2292</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Marion L Sanders, MD</last_name>
        <phone>319-338-0581</phone>
        <phone_ext>x635200</phone_ext>
        <email>marion.sanders2@va.gov</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE</name>
        <address>
          <city>Omaha</city>
          <state>Nebraska</state>
          <zip>68105-1850</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Roslyn B Mannon, MD</last_name>
        <phone>205-999-7362</phone>
        <email>roslyn.mannon@va.gov</email>
      </contact>
      <contact_backup>
        <last_name>Ramesh K Ramalingam</last_name>
        <phone>(402) 995-4873</phone>
        <email>Ramesh.Ramalingam@va.gov</email>
      </contact_backup>
      <investigator>
        <last_name>Roslyn B Mannon, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA</name>
        <address>
          <city>Pittsburgh</city>
          <state>Pennsylvania</state>
          <zip>15240</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Mohan Ramkumar, MBBS</last_name>
        <phone>412-360-3910</phone>
        <email>mohan.ramkumar@va.gov</email>
      </contact>
      <contact_backup>
        <last_name>Samantha Gray, MS</last_name>
        <phone>4123603788</phone>
        <email>Samantha.Gray6@va.gov</email>
      </contact_backup>
    </location>
    <location>
      <facility>
        <name>Tennessee Valley Healthcare System Nashville Campus, Nashville, TN</name>
        <address>
          <city>Nashville</city>
          <state>Tennessee</state>
          <zip>37212-2637</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Kelly Birdwell, MD</last_name>
        <phone>615-873-6974</phone>
        <email>kelly.birdwell@va.gov</email>
      </contact>
      <contact_backup>
        <last_name>Cindy A Mambungu, LPN</last_name>
        <phone>6153435828</phone>
        <email>cindy.mambungu@va.gov</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 22, 2023</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 28, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Transplant</keyword>
    <keyword>Diabetes</keyword>
    <keyword>Kidney Failure</keyword>
    <keyword>Rejection</keyword>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Empagliflozin</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06013865
  org study id: NEPH-008-22F
  secondary id: CSR&D
  nct id: NCT06013865
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  Kidney transplantation improves the health and quality of life for those Veterans with end
        stage kidney disease (ESKD). While early patient and graft survival are excellent, long-term
        outcomes continue to be challenging. Patient death with existing kidney graft function occurs
        in about half of all recipients over time. This is primarily due to the development of
        cardiovascular disease in a patient population with multiple preexisting cardiac disease risk
        factors. There has been little progress in improving outcomes in this area for over two
        decades. Recent studies in chronic kidney disease (CKD) patients using SGLT2 inhibitors
        (SGLT2i), regardless of the presence of type 2 diabetes mellitus (T2DM), results in both
        kidney protective and cardiac protective impacts and improved patient outcomes. However,
        kidney transplant recipients (KTRs) were excluded from these clinical trials due to concerns
        that these agents promote infection, diminish graft function, and may alter immunosuppressive
        drug levels that are the mainstay of patient's transplant therapy. There are limited
        published data of SGLT2i treatment of selected KTRs.
  Background: Kidney transplantation improves the health and quality of life for those veterans
        with end stage kidney disease (ESKD). While early patient and graft survival are excellent,
        long-term outcomes continue to be challenging. Patient death with existing kidney graft
        function occurs in about half of all recipients over time. This is primarily due to the
        development of cardiovascular disease in a patient population with multiple preexisting
        cardiac disease risk factors. There has been little progress in improving outcomes in this
        area for over two decades. Recent studies in chronic kidney disease (CKD) patients using
        SGLT2 inhibitors (SGLT2i), regardless of the presence of type 2 diabetes mellitus (T2DM),
        results in both kidney protective and cardiac protective impacts and improved patient
        outcomes. However, kidney transplant recipients (KTRs) were excluded from these clinical
        trials due to concerns that these agents promote infection, diminish graft function, and may
        alter immunosuppressive drug levels that are the mainstay of patient's transplant therapy.
        There are limited published data of SGLT2i treatment of selected KTRs.
  
        Objective: The goal of this submission is to examine the safety and efficacy of SGLT2i
        therapy in Veterans with KTRs and T2DM. The hypothesis is treatment with SGLT2i will lead to
        improvements in graft and cardiovascular outcomes in patients with T2DM, with acceptable side
        effect profile.
  
        Methods: To test this hypothesis, the investigators will execute a multicenter clinical trial
        at 4 VA medical centers, including 3 that serve as primary kidney transplant programs. The
        multidisciplinary research team includes transplant medical and surgical expertise,
        diabetology, and informatics and statistical support familiar with VA data systems. In open
        label fashion, the investigators will treat eligible KTRs and comprehensively assess adverse
        and serious adverse event data, as well as assess any untoward impacts on graft function and
        diabetes management. Secondly, the investigators will utilize VA data from the VINCI
        corporate data warehouse to develop a control cohort of Veterans with KTRs and T2DM, not
        treated with SGLT2i. The investigators will utilize propensity score matching to reduce bias
        that may occur in observational studies. With this strategy, the investigators will further
        address the potential beneficial impact of SGLT2i treatment on cardiovascular outcomes, as
        well as kidney disease progression in the transplanted kidney. The investigators will also
        analyze the cost impact of using this agent in this patient population, in terms of
        hospitalizations, unanticipated procedures, and CKD management.
  
        Findings: These studies will provide new information to the transplant community for both
        Veteran and non-Veteran alike, with a detailed assessment of safety and feasibility of this
        agent class using a pragmatic approach to transplant care. These results will translate into
        an opportunity to mitigate late graft loss in this patient population, and a potential
        breakthrough in clinical care that to date has been unrecognized.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: Prospective Observational Cohort Study
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Discontinuation of Empagliflozin
  time frame: about 2 years
  description: The incidence of therapeutic discontinuation of empagliflozin in the kidney transplant recipient from time of initiation.
  measure: Infection
  time frame: about 2 years
  description: Defined as the cumulative incidence of study defined Grade 3 or higher infection of the urinary tract or perineum after initiation of treatment.
  measure: Hypoglycemia
  time frame: about 2 years
  description: The cumulative incidence of grade 3 hypoglycemia
  measure: Major cardiorenal events
  time frame: about 2 years
  description: Time to first occurrence of the composite of major adverse cardiorenal events (MACER) as defined as all-cause mortality, stroke, non-fatal myocardial infarction, heart failure events including hospitalization for CHF or urgent CHF treatment, sustained (for at least 3 months) 40% decline in eGFR, or allograft failure as defined by chronic dialysis, re-transplantation, or persistent eGFR <15mL/min/1.73m2)
  measure: Acute Graft Dysfunction
  time frame: about 2 years
  description: The cumulative incidence of >15% elevation in serum creatinine for more than 4 weeks from the baseline defined prior to treatment.
  measure: Volume Depletion
  time frame: about 2 years
  description: The cumulative incidence of grade 3 volume depletion.
  measure: Acute Cellular Rejection
  time frame: about 2 years
  description: The cumulative incidence of acute rejection biopsy proven using 2017 criteria:
  Type IA Moderate tubulitis and at least moderate interstitial inflammation t2i2 or t2i3 Type IB Severe tubulitis and at least moderate interstitial inflammation t3i2 or t3i3 Type IIA Mild to moderate intimal arteritis v1 Type IIB Severe intimal arteritis (> 25% of the luminal area) v2 Type III Transmural' arteritis and/or fibrinoid necrosis v3 Borderline: no intimal arteritis is present, t>0 and i1 or i2/i3 and t1
  measure: Amputation and foot ulceration
  time frame: About 2 years
  description: The cumulative incidence of Grade 3 foot ulceration and/or need for amputation.
  measure: Proteinuria
  time frame: 12 and 24 months
  description: Spot Urine Protein/creatinine ratio
  measure: Allograft Biopsy
  time frame: about 2 years
  description: Time to incidence of a decline in eGFR sufficient to trigger a clinical decision for an allograft biopsy
  measure: MACER
  time frame: about 2 years
  description: Time to first occurrence of individual component of the MACER secondary outcome
  measure: Death
  time frame: about 2 years
  description: Time to the occurrence of cardiovascular death
  measure: Acute graft dysfunction
  time frame: About 2 years
  description: Time to acute kidney injury as defined as a >15% change in eGFR from baseline
  measure: Slope of kidney function
  time frame: over 2 years
  description: Serum creatinine measured in mg/dL for all participants prior to treatment, at month 6, month 12 and month 24 of treatment.
  measure: Glycemic Control
  time frame: over 2 years
  description: Changes in Hemoglobin A1C over time of treatment
  measure: Body Weight
  time frame: over 2 years
  description: Change in body weight over time of treatment
  measure: Blood Pressure
  time frame: over 2 years
  description: Change in blood pressure measured in mmHg over the course of the study
  arm group label: Empagliflozin
  arm group type: Other
  description: Open Label, Empagliflozin 12.5 mg QD
  intervention type: Drug
  intervention name: Empagliflozin
  description: SGLT2 Inhibitor
  arm group label: Empagliflozin
  other name: jardiance
  criteria: 
  gender: All
  minimum age: 19 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Roslyn B Mannon, MD
  role: Principal Investigator
  affiliation: Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE
  last name: Roslyn B Mannon, MD
  phone: (205) 999-7362
  email: roslyn.mannon@va.gov
  last name: Ramesh K Ramalingam
  phone: (402) 995-4873
  email: Ramesh.Ramalingam@va.gov
  facility: 
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  country: United States
  responsible party type: Sponsor
  mesh term: Empagliflozin
  sharing ipd: No