Budesonide for Immunosuppression After Liver Transplantation to Reduce Side Effects

Liver Transplant Rejection Clinical Trial

— BILT  

Official title:

Budesonide in Liver Transplantation

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03315052
• Other study ID #: 2017-7959
• Status: Withdrawn
• Phase: Phase 4
• Start date: January 2019
• Est. completion date: January 2022

Study information

• Verified date: September 2019
• Source: Montefiore Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2022
• Est. primary completion date: January 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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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

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Related Conditions & MeSH terms

• Acute Cellular Graft Rejection
• Liver Transplant Rejection

Intervention

Drug:
• Budesonide
Oral steroid with high first-pass metabolism in liver
• Tacrolimus(FK506)
Calcineurin immunosuppressant
• Mycophenolate Mofetil
Immunosupressant
• Prednisone
Immunosuppresant

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Montefiore Medical Center

References & Publications (6)

Bhat M, Ghali P, Wong P, Marcus V, Michel R, Cantarovich M, Metrakos P, Deschenes M. Immunosuppression with budesonide for liver transplant recipients with severe infections. Liver Transpl. 2012 Feb;18(2):262-3. doi: 10.1002/lt.22453. — View Citation

Jönsson G, Aström A, Andersson P. Budesonide is metabolized by cytochrome P450 3A (CYP3A) enzymes in human liver. Drug Metab Dispos. 1995 Jan;23(1):137-42. — View Citation

Lichtenstein GR, Travis S, Danese S, D'Haens G, Moro L, Jones R, Huang M, Ballard ED, Bagin R, Hardiman Y, Collazo R, Sandborn WJ. Budesonide MMX for the Induction of Remission of Mild to Moderate Ulcerative Colitis: A Pooled Safety Analysis. J Crohns Colitis. 2015 Sep;9(9):738-46. doi: 10.1093/ecco-jcc/jjv101. Epub 2015 Jun 20. — View Citation

Manns MP, Woynarowski M, Kreisel W, Lurie Y, Rust C, Zuckerman E, Bahr MJ, Günther R, Hultcrantz RW, Spengler U, Lohse AW, Szalay F, Färkkilä M, Pröls M, Strassburg CP; European AIH-BUC-Study Group. Budesonide induces remission more effectively than predn — View Citation

Ozcay N, Fryer J, Grant D, Freeman D, Garcia B, Zhong R. Budesonide, a locally acting steroid, prevents graft rejection in a rat model of intestinal transplantation. Transplantation. 1997 May 15;63(9):1220-5. — View Citation

Weber T, Kalbhenn T, Herrmann G, Hanisch E. Local immunosuppression with budesonide after liver transplantation in the rat: a preliminary histomorphological analysis. Transplantation. 1997 Sep 15;64(5):705-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute cellular rejection (ACR)	Incidence of ACR in budesonide treatment arm as compared to standard treatment arm	12 months
Secondary	Tacrolimus trough levels	Cumulative average trough level of tacrolimus in budesonide and standard treatment arms	12 months
Secondary	Diabetes	Incidence of diabetes in in budesonide and standard treatment arms	12 months
Secondary	Worsening kidney function	Incidence of worsening kidney function in budesonide and standard treatment arms	12 months
Secondary	Hyptertension	Incidence of hypertension in in budesonide and standard treatment arms	12 months
Secondary	Graft survival	Graft survival in budesonide and standard treatment arms	12 months
Secondary	Patient survival	Patient survival in budesonide and standard treatment arms	12 months
Secondary	Infection	Incidence of infection in budesonide and standard treatment arms	12 months