AzTrials
AzTrials

Acute Cellular Graft RejectionPhase 4BILTNCT03315052

Budesonide for Immunosuppression After Liver Transplantation to Reduce Side Effects

A Phase 4 study testing Budesonide, Tacrolimus（FK506） and Mycophenolate Mofetil in people with Acute Cellular Graft Rejection and Liver Transplant Rejection, run by Montefiore Medical Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Budesonide, Tacrolimus（FK506） and Mycophenolate Mofetil
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Jan 2019to Jan 2022
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

-

About this study

Official title: Budesonide in Liver Transplantation

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.

Read the 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

Being tested
Budesonide, Tacrolimus（FK506）, Mycophenolate Mofetil, Prednisone
Keywords
Graft loss, Renal failure, Infection, Diabetes, Hypertension
Medical subject headings
Renal Insufficiency, Infections, Diabetes Mellitus, Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BudesonideDrug

    Also called Enterocort

    Oral steroid with high first-pass metabolism in liver

  • Tacrolimus（FK506）Drug

    Also called Prograf

    Calcineurin immunosuppressant

  • Mycophenolate MofetilDrug

    Also called Cellcept

    Immunosupressant

  • PrednisoneDrug

    Immunosuppresant

Study groups in NCT03315052
Study groupRoleWhat they receive
Budesonide treatment armExperimentalPatients treated with budesonide in place of prednisone as part of immunosuppressive regimen
Receives: Drug: Budesonide; Drug: Tacrolimus（FK506）; Drug: Mycophenolate Mofetil
Standard immunosuppression armActive comparatorPatients treated with standard immunosuppression after liver transplant
Receives: Drug: Tacrolimus（FK506）; Drug: Mycophenolate Mofetil; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Acute cellular rejection (ACR)

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

    Measured: 12 months

Secondary outcomes (7)

  1. Tacrolimus trough levels

    Cumulative average trough level of tacrolimus in budesonide and standard treatment arms

    Measured: 12 months

  2. Diabetes

    Incidence of diabetes in in budesonide and standard treatment arms

    Measured: 12 months

  3. Worsening kidney function

    Incidence of worsening kidney function in budesonide and standard treatment arms

    Measured: 12 months

  4. Hyptertension

    Incidence of hypertension in in budesonide and standard treatment arms

    Measured: 12 months

  5. Graft survival

    Graft survival in budesonide and standard treatment arms

    Measured: 12 months

  6. Patient survival

    Patient survival in budesonide and standard treatment arms

    Measured: 12 months

  7. Infection

    Incidence of infection in budesonide and standard treatment arms

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Oct 2017
  2. Study startJan 2019 (estimated)
  3. Primary completionJan 2021 (estimated)
  4. Study completionJan 2022 (estimated)

Why it stopped: Delay in IRB approval

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Model description
Comparison of standard immunosuppression to immunosuppression incorporating budesonide in place of prednisone
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03315052
Sponsor's protocol ID
2017-7959
Acronym
BILT
Status last verified
Sep 2019
First submitted
13 Oct 2017
Last updated
23 Sep 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided: Annonymous IPD will be shared in the event that the study protocol is approved at other transplanting institutions who then collaborate in this study. IPD will include standard clinical and laboratory data monitored after liver transplantation

Publications

  • 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.

    PubMed 7720517

  • 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.

    PubMed 9311706

  • 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.

    PubMed 9158013

  • 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.

    PubMed 22006869

  • 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.

    PubMed 26094251

  • 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.

    PubMed 20600032

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Budesonide, Tacrolimus（FK506） and Mycophenolate Mofetil in people with Acute Cellular Graft Rejection and Liver Transplant Rejection, run by Montefiore Medical Center.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 23 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Acute cellular rejection (ACR) (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03315052, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in