Biomarkers Predicting Successful Tacrolimus Withdrawal and Everolimus (Zortress) Monotherapy Early After Liver Transplantation

Northwestern University28 enrolled

Overview

Most patients who get a liver transplant must take immunosuppressants for the rest of their lives. However, this has occurred at the expense of chronic CNI toxicity, e.g. chronic kidney disease (CKD), metabolic complications, infections and malignancy. Everolimus (EVL) is a drug that may stabilize or improve kidney function for patients with chronic kidney disease (CKD) that has been caused by immunosuppressants. EVL is used for standard of care treatment to prevent transplant liver rejection in combination with other immunosuppressants, such as tacrolimus. The overall aim of this study is to examine a combination of two different immunosuppressants and EVL to determine if patients may have stabilized and/or improved kidney function without liver rejection. This study will look at how safe it is to slowly withdraw one anti-rejection medication while continuing to take the other medicine, and whether this can be done without liver rejection occurrence.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Liver Transplantation

Interventions

During the first month post-transplant, the subject receives everolimus (about 5-8 ng/mL) and tacrolimus with or without mycophenolic acid as part of standard of care procedures. At one month post-transplant, mycophenolic acid will be stopped and tacrolimus dosage will be reduced while continuing the dosage of everolimus. At three months post-transplant, tacrolimus dosage will be reduced by 50% of the daily dose each week. At four months post-transplant, tacrolimus will be discontinued.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 89 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adult LT candidates ≥ 18 years of age * Listed for or recent (within 1 month) recipient of deceased or living donor liver transplantation Exclusion Criteria: * Combined or previous organ transplantation * Human immunodeficiency virus (HIV) infection * Inability to provide informed consent or comply with the protocol.

Outcomes

Primary Outcomes

Amount of Treg Cells Observed in Peripheral Blood in Patients With and Without Rejection

flow cytometry immunophenotyping and gene expression microassays to assess amount of Treg cells and mRNA in peripheral blood in patients with and without rejection (after Tacc withdrwal)

Time frame: Six months post transplantation