Empagliflozin Treatment in Kidney Transplant Recipients (SEKTR)

VA Office of Research and Development

Status and phase

Enrolling

Phase 4

Conditions

Chronic Kidney Disease

Kidney Transplant

Treatments

Drug: Empagliflozin

Study type

Interventional

Funder types

Other U.S. Federal agency

Other

Identifiers

NCT06013865

NEPH-008-22F

CSR&D (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment

264 estimated patients

Sex

All

Ages

19+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Adult (>18 years of age) male and female recipients (all races and ethnicities)
Subject must be able to understand and provide consent
Recipient of a primary or secondary kidney transplant at least 3 months or longer since transplant
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).
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

Inability or unwillingness of a participant to give written informed consent or comply with study protocol
History of prior pancreas transplant
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
Uncontrolled type 2 diabetes mellitus with most recent A1C>12%
History of >2 urinary tract infections per year or UTIs requiring admission in the last year, or urosepsis in the last year.
Use of SGLT2i within 90 days
Documented allergy to SGLT2i
History of Type I diabetes mellitus
History of diabetic ketoacidosis
Indwelling foley catheter or urinary diversion
Acute rejection in the prior 3 months
Acute MACE event within 3 months of the study
Severe congestive heart failure (NYHA functional class III or higher)
Active mucocutaneous mycotic infection of the groin or external genitalia.
History of amputation due to peripheral vascular disease and/or diabetic foot ulcers within prior year
History of malignancy except non-melanoma skin cancer within 2 years of screening
Known of active current viral, fungal, mycobacterial, or other infections (including, but not limited to tuberculosis and atypical mycobacterial disease)
HIV infected subjects, including those who are well controlled on anti-retrovirals
Recent (within 6 months) Positive Hep B PCR or active disease
Hepatitis C virus antibody positive (HCVAb+) subjects who have failed to demonstrate sustained viral remission for more than 12 weeks (after anti-viral treatment)
Active pregnancy in a female transplant recipient
A condition, in the eyes of the investigator, that precludes inclusion into the study.