Budesonide for Immunosuppression After Liver Transplantation to Reduce Side Effects
- Conditions
- Acute Cellular Graft RejectionLiver Transplant Rejection
- Interventions
- Registration Number
- NCT03315052
- Lead Sponsor
- Montefiore Medical Center
- Brief Summary
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
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
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
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.
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Budesonide treatment arm Tacrolimus（FK506） Patients treated with budesonide in place of prednisone as part of immunosuppressive regimen Standard immunosuppression arm Tacrolimus（FK506） Patients treated with standard immunosuppression after liver transplant Standard immunosuppression arm Mycophenolate Mofetil Patients treated with standard immunosuppression after liver transplant Budesonide treatment arm Mycophenolate Mofetil Patients treated with budesonide in place of prednisone as part of immunosuppressive regimen Budesonide treatment arm Budesonide Patients treated with budesonide in place of prednisone as part of immunosuppressive regimen Standard immunosuppression arm Prednisone Patients treated with standard immunosuppression after liver transplant
- Primary Outcome Measures
Name Time Method Acute cellular rejection (ACR) 12 months Incidence of ACR in budesonide treatment arm as compared to standard treatment arm
- Secondary Outcome Measures
Name Time Method Tacrolimus trough levels 12 months Cumulative average trough level of tacrolimus in budesonide and standard treatment arms
Diabetes 12 months Incidence of diabetes in in budesonide and standard treatment arms
Worsening kidney function 12 months Incidence of worsening kidney function in budesonide and standard treatment arms
Hyptertension 12 months Incidence of hypertension in in budesonide and standard treatment arms
Graft survival 12 months Graft survival in budesonide and standard treatment arms
Patient survival 12 months Patient survival in budesonide and standard treatment arms
Infection 12 months Incidence of infection in budesonide and standard treatment arms