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

Sponsor

Northwestern University (Other)

Overall Status

Completed

CT.gov ID

NCT02736227

Collaborator

Novartis Pharmaceuticals (Industry)

Enrollment

Location

Arm

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Liver Transplantation	Drug: Tacrolimus Withdrawal and Everolimus Monotherapy	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2016

Actual Primary Completion Date :

Mar 1, 2021

Actual Study Completion Date :

Mar 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tacrolimus Withdrawal and Everolimus Monotherapy Tacrolimus will be tapered while continual use of everolimus.	Drug: Tacrolimus Withdrawal and Everolimus Monotherapy 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.

Arm

Intervention/Treatment

Experimental: Tacrolimus Withdrawal and Everolimus Monotherapy

Tacrolimus will be tapered while continual use of everolimus.

Drug: Tacrolimus Withdrawal and Everolimus Monotherapy

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.

Outcome Measures

Primary Outcome Measures

Amount of Treg cells and mRNA observed in peripheral blood prior to and during tacrolimus withdrawal plus everolimus treatment. [Six months post transplantation]
Sequential flow cytometry immunophenotyping and gene expression microassays

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 89 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University Comprehensive Transplant Center	Chicago	Illinois	United States	60611

Sponsors and Collaborators

Northwestern University
Novartis Pharmaceuticals

Investigators

Principal Investigator: Josh Levitsky, MD, MS, Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Josh Levitsky, Associate Professor in Medicine-Gastroenterology and Hepatology and Surgery-Organ Transplantation, Northwestern University

ClinicalTrials.gov Identifier:

NCT02736227

Other Study ID Numbers:

STU00201794

First Posted:

Apr 13, 2016

Last Update Posted:

Apr 8, 2021

Last Verified:

Apr 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Keywords provided by Josh Levitsky, Associate Professor in Medicine-Gastroenterology and Hepatology and Surgery-Organ Transplantation, Northwestern University

liver transplantation

Additional relevant MeSH terms:

Everolimus

Tacrolimus

Study Results

No Results Posted as of Apr 8, 2021