Acute Cellular Graft Rejection, Liver Transplant Rejection
Conditions
Keywords
Graft loss, Renal failure, Infection, Diabetes, Hypertension
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
Interventions
DRUGBudesonide
Oral steroid with high first-pass metabolism in liver
Calcineurin immunosuppressant
DRUGMycophenolate Mofetil
Immunosupressant
DRUGPrednisone
Immunosuppresant
Sponsors
Montefiore Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Comparison of standard immunosuppression to immunosuppression incorporating budesonide in place of prednisone
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acute cellular rejection (ACR) | 12 months | Incidence of ACR in budesonide treatment arm as compared to standard treatment arm |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Tacrolimus trough levels | 12 months | Cumulative average trough level of tacrolimus 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 |
| Graft survival | 12 months | Graft survival in budesonide and standard treatment arms |
Outcome results
None listed