Budesonide for Immunosuppression After Liver Transplantation to Reduce Side Effects

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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Budesonide in Liver Transplantation

Conditions
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Acute Cellular Graft Rejection, Liver Transplant Rejection

Intervention / Treatment
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* Drug: Budesonide
* Drug: Tacrolimus（FK506）
* Drug: Mycophenolate Mofetil
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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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 -

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Comparison of standard immunosuppression to immunosuppression incorporating budesonide in place of prednisone
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Budesonide treatment arm<br>Patients treated with budesonide in place of prednisone as part of immunosuppressive regimen | Drug: Budesonide<br>* Oral steroid with high first-pass metabolism in liver<br>* Other names: Enterocort;Drug: Tacrolimus（FK506）<br>* Calcineurin immunosuppressant<br>* Other names: Prograf;Drug: Mycophenolate Mofetil<br>* Immunosupressant<br>* Other names: Cellcept;|
| Active Comparator: Standard immunosuppression arm<br>Patients treated with standard immunosuppression after liver transplant | Drug: Tacrolimus（FK506）<br>* Calcineurin immunosuppressant<br>* Other names: Prograf;Drug: Mycophenolate Mofetil<br>* Immunosupressant<br>* Other names: Cellcept;Drug: Prednisone<br>* Immunosuppresant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute cellular rejection (ACR) | Incidence of ACR in budesonide treatment arm as compared to standard treatment arm | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tacrolimus trough levels | Cumulative average trough level of tacrolimus in budesonide and standard treatment arms | 12 months | 
| Diabetes | Incidence of diabetes in in budesonide and standard treatment arms | 12 months | 
| Worsening kidney function | Incidence of worsening kidney function in budesonide and standard treatment arms | 12 months | 
| Hyptertension | Incidence of hypertension in in budesonide and standard treatment arms | 12 months | 
| Graft survival | Graft survival in budesonide and standard treatment arms | 12 months | 
| Patient survival | Patient survival in budesonide and standard treatment arms | 12 months | 
| Infection | Incidence of infection in budesonide and standard treatment arms | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Graft loss, Renal failure, Infection, Diabetes, Hypertension