Mycophenolate Mofetil Immunosuppression Without/With Reduced Dose Calcineurin Inhibitor Long After Liver Transplantation

NCT00206076 | Completed Phase 4 Results

• 1 other identifier: CEL350
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of the study is to assess the safety and efficacy of mycophenolate mofetil alone, or with reduced dose cyclosporine (CsA) or tacrolimus, for immunosuppression long-term after liver transplantation, in an attempt to reduce the potential side effects from using cyclosporine or tacrolimus.

Conditions

Liver Disease

Keywords

Liver transplantation; Calcineurin inhibitor withdraw; mycophenolate mofetil; Immunosuppression side effects; Graft rejection

Outcome Measures

Primary Outcomes (1)

• Number of Biopsy Proven Rejections at 12 Months

  assessed by liver biopsy using Banff International Consensus Schema

  12 months

Secondary Outcomes (2)

• Patient and Graft Survival at 12 Months

  12 months

• Number of Participants With Adverse Events Including Infections at 12 Months

  12 months

Study Arms (2)

1

EXPERIMENTAL

mycophenolate mofetil monotherapy

Drug: mycophenolate mofetil

2

ACTIVE COMPARATOR

mycophenolate mofetil and half their baseline dose of calcineurin inhibitor

Drug: mycophenolate mofetil

Interventions

mycophenolate mofetil DRUG

mycophenolate mofetil and half their baseline dose of calcineurin inhibitor

2

Eligibility Criteria

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

You may qualify if:

• Male or female 18 years of age or older (females who can become pregnant must use two acceptable methods of birth control while taking mycophenolate mofetil)
• Orthotopic liver transplant more than one year prior to enrollment
• Using calcineurin inhibitor to prevent rejection at time of screening
• Patients must be willing to provide informed consent and abide by the requirements of the study

You may not qualify if:

• Liver disease may not have been secondary to an autoimmune cause, including:
• autoimmune hepatitis,
• primary sclerosing cholangitis,
• primary biliary cirrhosis
• Patients who have had:
• more than one prior episode of rejection,
• rejection within the past six months,
• any corticosteroid resistant rejection
• Patients with a tacrolimus trough level of greater than 7 ng/ml within 90 days prior to enrollment
• Patients with a cyclosporine trough level greater than 225 ng/ml within 90 days prior to enrollment
• Patients taking more the 5 mg per day of prednisone within 90 days prior to enrollment
• Patients taking any prednisone within 30 days of enrollment
• Allograft dysfunction within 6 months of enrollment, including ALT and/or total bilirubin greater than 2x normal, and/or biopsy proven hepatitis C virus (HCV) with fibrosis greater than stage II
• White blood cell count less than 2,500 or platelet count less than 50,000 within 60 days of enrollment
• MPA AUC threshold: Patients are not eligible for the study if they do not attain the threshold value MPA AUC (\>30 mg\*h/L if on CsA, \>40 mg\*h/L if on tacrolimus) after 50% calcineurin inhibitor reduction, measured using a 3-sample estimate (trough, 30-min, 120-min)

Sponsors & Collaborators

• Albert Einstein Healthcare Network: lead
• Hoffmann-La Roche: collaborator

Study Sites (3)

University of Kentucky at Lexington

Lexington, Kentucky, United States

Location

Albert Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

Texas Transplant Institute

San Antonio, Texas, United States

Location

Related Publications (14)

• Reich DJ, Clavien PA, Hodge EE; MMF Renal Dysfunction after Liver Transplantation Working Group. Mycophenolate mofetil for renal dysfunction in liver transplant recipients on cyclosporine or tacrolimus: randomized, prospective, multicenter pilot study results. Transplantation. 2005 Jul 15;80(1):18-25. doi: 10.1097/01.tp.0000165118.00988.d7.

  PMID: 16003228 BACKGROUND

• Reich D, Rothstein K, Manzarbeitia C, Munoz S. Common medical diseases after liver transplantation. Semin Gastrointest Dis. 1998 Jul;9(3):110-25.

  PMID: 9700842 BACKGROUND

• Mazariegos GV, Reyes J, Marino IR, Demetris AJ, Flynn B, Irish W, McMichael J, Fung JJ, Starzl TE. Weaning of immunosuppression in liver transplant recipients. Transplantation. 1997 Jan 27;63(2):243-9. doi: 10.1097/00007890-199701270-00012.

  PMID: 9020325 BACKGROUND

• McDiarmid SV, Farmer DA, Goldstein LI, Martin P, Vargas J, Tipton JR, Simmons F, Busuttil RW. A randomized prospective trial of steroid withdrawal after liver transplantation. Transplantation. 1995 Dec 27;60(12):1443-50. doi: 10.1097/00007890-199560120-00013.

  PMID: 8545872 BACKGROUND

• Fraser GM, Grammoustianos K, Reddy J, Rolles K, Davidson B, Burroughs AK. Long-term immunosuppression without corticosteroids after orthotopic liver transplantation: a positive therapeutic aim. Liver Transpl Surg. 1996 Nov;2(6):411-7. doi: 10.1002/lt.500020602.

  PMID: 9346686 BACKGROUND

• Stegall MD, Everson GT, Schroter G, Karrer F, Bilir B, Sternberg T, Shrestha R, Wachs M, Kam I. Prednisone withdrawal late after adult liver transplantation reduces diabetes, hypertension, and hypercholesterolemia without causing graft loss. Hepatology. 1997 Jan;25(1):173-7. doi: 10.1002/hep.510250132.

  PMID: 8985286 BACKGROUND

• Hodge EE, Reich DJ, Clavien PA, Kim-Schluger L. Use of mycophenolate mofetil in liver transplant recipients experiencing renal dysfunction on cyclosporine or tacrolimus-randomized, prospective, multicenter study results. Transplant Proc. 2002 Aug;34(5):1546-7. doi: 10.1016/s0041-1345(02)03014-2. No abstract available.

  PMID: 12176477 BACKGROUND

• Raimondo ML, Dagher L, Papatheodoridis GV, Rolando N, Patch DW, Davidson BR, Rolles K, Burroughs AK. Long-term mycophenolate mofetil monotherapy in combination with calcineurin inhibitors for chronic renal dysfunction after liver transplantation. Transplantation. 2003 Jan 27;75(2):186-90. doi: 10.1097/01.TP.0000041702.31262.CD.

  PMID: 12548120 BACKGROUND

• Schlitt HJ, Barkmann A, Boker KH, Schmidt HH, Emmanouilidis N, Rosenau J, Bahr MJ, Tusch G, Manns MP, Nashan B, Klempnauer J. Replacement of calcineurin inhibitors with mycophenolate mofetil in liver-transplant patients with renal dysfunction: a randomised controlled study. Lancet. 2001 Feb 24;357(9256):587-91. doi: 10.1016/s0140-6736(00)04055-1.

  PMID: 11558484 BACKGROUND

• Herrero JI, Quiroga J, Sangro B, Girala M, Gomez-Manero N, Pardo F, Alvarez-Cienfuegos J, Prieto J. Conversion of liver transplant recipients on cyclosporine with renal impairment to mycophenolate mofetil. Liver Transpl Surg. 1999 Sep;5(5):414-20. doi: 10.1002/lt.500050513.

  PMID: 10477843 BACKGROUND

• Stewart SF, Hudson M, Talbot D, Manas D, Day CP. Mycophenolate mofetil monotherapy in liver transplantation. Lancet. 2001 Feb 24;357(9256):609-10. doi: 10.1016/s0140-6736(00)04065-4.

  PMID: 11558493 BACKGROUND

• Munoz SJ, Rothstein KD, Reich D, Manzarbeitia C. Long-term care of the liver transplant recipient. Clin Liver Dis. 2000 Aug;4(3):691-710. doi: 10.1016/s1089-3261(05)70133-1.

  PMID: 11232168 BACKGROUND

• Wiesner R, Rabkin J, Klintmalm G, McDiarmid S, Langnas A, Punch J, McMaster P, Kalayoglu M, Levy G, Freeman R, Bismuth H, Neuhaus P, Mamelok R, Wang W. A randomized double-blind comparative study of mycophenolate mofetil and azathioprine in combination with cyclosporine and corticosteroids in primary liver transplant recipients. Liver Transpl. 2001 May;7(5):442-50. doi: 10.1053/jlts.2001.23356.

  PMID: 11349266 BACKGROUND

• Shaw LM, Korecka M, Venkataramanan R, Goldberg L, Bloom R, Brayman KL. Mycophenolic acid pharmacodynamics and pharmacokinetics provide a basis for rational monitoring strategies. Am J Transplant. 2003 May;3(5):534-42. doi: 10.1034/j.1600-6143.2003.00079.x. No abstract available.

  PMID: 12752309 BACKGROUND

MeSH Terms

Conditions

Liver Diseases

Interventions

Mycophenolic Acid

Condition Hierarchy (Ancestors)

Digestive System Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Results Point of Contact

• Title: David Reich, MD
• Organization: Drexel University College of Medicine

David.Reich@DrexelMed.edu

215-762-7143

Study Officials

• David J Reich, MD

  Drexel College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 21, 2005
• Study Start: August 1, 2006
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: August 2, 2013
• Results First Posted: August 2, 2013

Record last verified: 2013-07

Locations

US (3)