An Exploratory Investigation of the Safety of Empagliflozin in Kidney Transplant Recipients (SEKTR)

NEPH-008-22F

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.

2024-04-05

2030-03-31

2030-03-31

Recruiting

Early phase I

264

Inclusion 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. Subject must have a diagnosis of Type 2 Diabetes Mellitus or post-transplant diabetes mellitus (PTDM) 2DM or PTDM 5. Subject must be able to travel to and from VAMC for care and monitoring 6. Subject must have kidney function measured by CKD epi eGFR 30 mL/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: 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 with 5mL/min/1.73m2 fall 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 5 years of screening 17. Known 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. Positive Hep B PCR 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

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2024-05-16