Budesonide for Immunosuppression After Liver Transplantation to Reduce Side Effects

Montefiore Medical Center

Overview

Our hypothesis is that budesonide will provide effective hepatic ISP that will replace prednisone and allow lower systemic drug levels of FK, thus reducing the steroid- and calcineurin-associated complications often observed in the OLT population. This study is intended to investigate the therapeutic potential of this ISP combination.

This study will be a randomized, open-label non-inferiority trial to assess the efficacy, safety and tolerability of budesonide in combination with low-dose FK and standard-dose MMF as post-OLT ISP in comparison to standard ISP (S-ISP). Subjects will include OLT patients age 18 years and older receiving their first single-organ living- or deceased-donor liver transplant. Subjects must have post-operative recovery of graft function and be able to take oral medications before beginning treatment according to the study protocol. Subjects will be randomized to receive either (1) investigational oral ISP including budesonide 9mg by mouth in three daily divided doses, FK with an initial target trough level of no greater than 5-6ng/mL, and MMF (I-ISP); or (2) S-ISP including prednisone, calcineurin antagonist, and MMF. After randomization, subjects will be followed for a total of 52 weeks and assessed for adequacy of graft function, and complications of therapy, particularly ACR

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Conditions

Acute Cellular Graft Rejection Liver Transplant Rejection

Interventions

BudesonideDRUG

Oral steroid with high first-pass metabolism in liver

Tacrolimus（FK506）DRUG

Calcineurin immunosuppressant

Mycophenolate MofetilDRUG

Immunosupressant

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: Adult patients age 18 years or older who undergo initial single-organ living- or deceased-donor liver-transplant surgery. Research participants are required to have satisfactory post-operative recovery of graft function and no post-operative renal-replacement therapy prior to starting medication according to protocol. They must also be able to take oral medications. \- Exclusion Criteria: Patients will be excluded from the study if they are: (1) undergoing retransplantation; (2) have fulminant hepatic failure as an indication for liver transplantation; (3) have surgical complication(s) potentially affecting post-operative graft function (i.e., hepatic artery thrombosis); or have delayed initial recovery of graft function (primary non-function) requiring non-standard induction therapy. Furthermore, patients with a contraindication to budesonide (i.e., hypersensitivity) will not be included in the study \-

Outcomes

Primary Outcomes

Acute cellular rejection (ACR)

Incidence of ACR in budesonide treatment arm as compared to standard treatment arm

Time frame: 12 months

Secondary Outcomes

Tacrolimus trough levels

Cumulative average trough level of tacrolimus in budesonide and standard treatment arms

Time frame: 12 months

Diabetes

Incidence of diabetes in in budesonide and standard treatment arms

Time frame: 12 months

Worsening kidney function

Incidence of worsening kidney function in budesonide and standard treatment arms

Time frame: 12 months

Hyptertension

Incidence of hypertension in in budesonide and standard treatment arms

Time frame: 12 months

Graft survival

Graft survival in budesonide and standard treatment arms

Time frame: 12 months

Patient survival

Patient survival in budesonide and standard treatment arms

Time frame: 12 months

Infection

Incidence of infection in budesonide and standard treatment arms

Time frame: 12 months

Data from ClinicalTrials.gov

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