Empagliflozin Treatment in Kidney Transplant Recipients

NCT ID: NCT06013865

Last Updated: 2025-05-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 264 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-05
• Study Completion Date: 2030-03-31

Brief Summary

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.

Detailed Description

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 with and without T2DM. The hypothesis is treatment with SGLT2i will lead to improvements in graft and cardiovascular outcomes in patients with chronic kidney disease, with acceptable side effect profile.

Methods: To test this hypothesis, the investigators will execute a multicenter clinical trial at 5 VA medical centers, including 4 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 with and without 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.

Conditions

Kidney Transplant; Chronic Kidney Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Empagliflozin

Open Label, Empagliflozin 12.5 mg QD

Group Type: OTHER

Empagliflozin

Intervention Type: DRUG

SGLT2 Inhibitor

Interventions

Empagliflozin

SGLT2 Inhibitor

Intervention Type: DRUG

Other Intervention Names

jardiance

Eligibility Criteria

Inclusion Criteria

1. Adult (>18 years of age) male and female recipients (all races and ethnicities)

2. Subject must be able to understand and provide consent

3. Recipient of a primary or secondary kidney transplant at least 3 months or longer since transplant

4. For subjects with T2DM or post-transplant diabetes (PTDM), measured kidney function by CKD epi eGFR must be 30mL/min/1.73m2 to < 45ml/min/1.73m2 or CKD epi eGFR 45 mL/min/1.73m2 to 90ml/min/1.73m2 with urinary albumin:creatinine ratio 200 mg/g (or protein:creatinine 300 mg/g).

5. For subjects without T2DM or PTDM: measured kidney function by CKD epi eGFR must be 20mL/min/1.73m2 to < 45ml/min/1.73m2 or CKD epi eGFR 45 mL/min/1.73m2 to 90ml/min/1.73m2 with urinary albumin:creatinine ratio 200 mg/g (or protein:creatinine 300 mg/g).

Exclusion Criteria

1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol

2. History of prior pancreas transplant

3. CKD epi eGFR < 30 mL/min/1.73m2 for those with T2DM or < 20 mL/min/1.73m2 for those without T2DM or anyone with 5mL/min/1.73m2 fall in eGFR per year

4. Uncontrolled type 2 diabetes mellitus with most recent A1C>12%

5. History of >2 urinary tract infections per year or UTIs requiring admission in the last year, or urosepsis in the last year.

6. Use of SGLT2i within 90 days

7. Documented allergy to SGLT2i

8. History of Type I diabetes mellitus

9. History of diabetic ketoacidosis

10. Indwelling foley catheter or urinary diversion

11. Acute rejection in the prior 3 months

12. Acute MACE event within 3 months of the study

13. Severe congestive heart failure (NYHA functional class III or higher)

14. Active mucocutaneous mycotic infection of the groin or external genitalia.

15. History of amputation due to peripheral vascular disease and/or diabetic foot ulcers within prior year

16. History of malignancy except non-melanoma skin cancer within 2 years of screening

17. Known of active current viral, fungal, mycobacterial, or other infections (including, but not limited to tuberculosis and atypical mycobacterial disease)

18. HIV infected subjects, including those who are well controlled on anti-retrovirals

19. Recent (within 6 months) Positive Hep B PCR or active disease

20. Hepatitis C virus antibody positive (HCVAb+) subjects who have failed to demonstrate sustained viral remission for more than 12 weeks (after anti-viral treatment)

21. Active pregnancy in a female transplant recipient

22. A condition, in the eyes of the investigator, that precludes inclusion into the study.

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Iowa City VA Health Care System

FED

Sponsor Role: collaborator

VA Pittsburgh Healthcare System

FED

Sponsor Role: collaborator

VA Tennessee Valley Health Care System

FED

Sponsor Role: collaborator

VA Hines Health Care

UNKNOWN

Sponsor Role: collaborator

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roslyn B Mannon, MD

Role: PRINCIPAL_INVESTIGATOR

Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE

Locations

Edward Hines Jr. VA Hospital, Hines, IL

Hines, Illinois, United States

Site Status: NOT_YET_RECRUITING

Iowa City VA Health Care System, Iowa City, IA

Iowa City, Iowa, United States

Site Status: RECRUITING

Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE

Omaha, Nebraska, United States

Site Status: RECRUITING

VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Pittsburgh, Pennsylvania, United States

Site Status: RECRUITING

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Nashville, Tennessee, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Roslyn B Mannon, MD

Role: CONTACT

roslyn.mannon@va.gov

(205) 999-7362

Ramesh K Ramalingam

Role: CONTACT

Ramesh.Ramalingam@va.gov

(402) 995-4873

Facility Contacts

Rapahel Lopez-Soler, MD

Role: primary

reynold.lopez-soler@va.gov

Marion L Sanders, MD

Role: primary

marion.sanders2@va.gov

319-338-0581 ext. x635200

Roslyn B Mannon, MD

Role: primary

roslyn.mannon@va.gov

205-999-7362

Ramesh K Ramalingam

Role: backup

Ramesh.Ramalingam@va.gov

(402) 995-4873

Mohan Ramkumar, MBBS

Role: primary

mohan.ramkumar@va.gov

412-360-3910

Samantha Gray, MS

Role: backup

Samantha.Gray6@va.gov

4123603788

Kelly Birdwell, MD

Role: primary

kelly.birdwell@va.gov

615-873-6974

Cindy A Mambungu, LPN

Role: backup

cindy.mambungu@va.gov

6153435828

Other Identifiers

CSR&D

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

NEPH-008-22F

Identifier Type: -

Identifier Source: org_study_id