Budesonide for Immunosuppression After Liver Transplantation to Reduce Side Effects

NCT03315052 | Withdrawn Phase 4 DMC FDA Drug

• 1 other identifier: 2017-7959
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Acute Cellular Graft Rejection; Liver Transplant Rejection

Keywords

Graft loss; Renal failure; Infection; Diabetes; Hypertension

Outcome Measures

Primary Outcomes (1)

• Acute cellular rejection (ACR)

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

  12 months

Secondary Outcomes (7)

• Tacrolimus trough levels

  12 months

• Diabetes

  12 months

• Worsening kidney function

  12 months

• Hyptertension

  12 months

• Graft survival

  12 months

Study Arms (2)

Budesonide treatment arm

EXPERIMENTAL

Patients treated with budesonide in place of prednisone as part of immunosuppressive regimen

Drug: Budesonide; Drug: Tacrolimus（FK506）; Drug: Mycophenolate Mofetil

Standard immunosuppression arm

ACTIVE COMPARATOR

Patients treated with standard immunosuppression after liver transplant

Drug: Tacrolimus（FK506）; Drug: Mycophenolate Mofetil; Drug: Prednisone

Interventions

Budesonide DRUG

Oral steroid with high first-pass metabolism in liver

Also known as: Enterocort

Budesonide treatment arm

Tacrolimus（FK506） DRUG

Calcineurin immunosuppressant

Also known as: Prograf

Budesonide treatment arm; Standard immunosuppression arm

Mycophenolate Mofetil DRUG

Immunosupressant

Also known as: Cellcept

Budesonide treatment arm; Standard immunosuppression arm

Prednisone DRUG

Immunosuppresant

Standard immunosuppression arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Sponsors & Collaborators

• Montefiore Medical Center: lead

Related Publications (6)

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

  PMID: 7720517 BACKGROUND

• 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. doi: 10.1097/00007890-199709150-00007.

  PMID: 9311706 BACKGROUND

• 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. doi: 10.1097/00007890-199705150-00006.

  PMID: 9158013 BACKGROUND

• 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. No abstract available.

  PMID: 22006869 BACKGROUND

• 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.

  PMID: 26094251 BACKGROUND

• Manns MP, Woynarowski M, Kreisel W, Lurie Y, Rust C, Zuckerman E, Bahr MJ, Gunther R, Hultcrantz RW, Spengler U, Lohse AW, Szalay F, Farkkila M, Prols M, Strassburg CP; European AIH-BUC-Study Group. Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis. Gastroenterology. 2010 Oct;139(4):1198-206. doi: 10.1053/j.gastro.2010.06.046. Epub 2010 Jun 22.

  PMID: 20600032 RESULT

MeSH Terms

Conditions

Renal Insufficiency; Infections; Diabetes Mellitus; Hypertension

Interventions

Budesonide; Tacrolimus; Mycophenolic Acid; Prednisone

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Pregnadienediols; Pregnadienes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Comparison of standard immunosuppression to immunosuppression incorporating budesonide in place of prednisone

Study Record Dates

• First Submitted: October 13, 2017
• First Posted: October 19, 2017
• Study Start: January 1, 2019
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2022
• Last Updated: September 23, 2019

Record last verified: 2019-09