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

Study Overview
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Brief Summary
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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.

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

Conditions
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Liver Transplantation

Intervention / Treatment
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* Drug: Tacrolimus Withdrawal and Everolimus Monotherapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tacrolimus Withdrawal and Everolimus Monotherapy<br>Tacrolimus will be tapered while continual use of everolimus. | Drug: Tacrolimus Withdrawal and Everolimus Monotherapy<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | Six months post transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver transplantation, immunosuppression, everolimus, tacrolimus, kidney function, liver function, biomarkers