Liver Spare the Nephron (STN) Study - A Study of CellCept (Mycophenolate Mofetil) and Sirolimus in Recipients of a Liver Transplant

A Randomized, Open-label Study of the Effect of a Long-term Calcineurin Inhibitor-free Maintenance Regimen With CellCept and Sirolimus on Preservation of Renal Function and Prevention of Acute Rejection in Recipients of an Orthotropic Liver Transplant

This two-arm study will assess the efficacy and safety of a long-term calcineurin inhibitor-free maintenance regimen with CellCept and sirolimus in recipients of an orthotropic liver transplant. Patients will be randomized to receive either CellCept 1-1.5 g twice daily (BID) + tacrolimus + cyclosporine, or CellCept 1-1.5 g BID + sirolimus. The anticipated time on study treatment is 1 to 2 years, and the target sample size is 100 to 500 individuals.

Study Overview

• Status: Completed
• Conditions: Liver Transplantation
• Intervention / Treatment: Drug: mycophenolate mofetil [CellCept]; Drug: Tacrolimus; Drug: Cyclosporine; Drug: Sirolimus

• Study Type: Interventional
• Enrollment (Actual): 293
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
  • Ontario
    • London, Ontario, Canada, N6A 5A5
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
    • Montreal, Quebec, Canada, H2X 3J4
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
  • Arizona
    • Phoenix, Arizona, United States, 85054
  • California
    • La Jolla, California, United States, 92037
    • Los Angeles, California, United States, 90095
    • Los Angeles, California, United States, 90033-4612
    • San Diego, California, United States, 92103-8401
    • San Francisco, California, United States, 94115
    • San Francisco, California, United States, 94143-0780
  • Colorado
    • Denver, Colorado, United States, 80262
  • Florida
    • Jacksonville, Florida, United States, 32216
    • Miami, Florida, United States, 33136
    • Tampa, Florida, United States, 33606
  • Georgia
    • Atlanta, Georgia, United States, 30322
  • Illinois
    • Chicago, Illinois, United States, 60611
    • Chicago, Illinois, United States, 60612-3824
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
  • Maryland
    • Baltimore, Maryland, United States, 21201
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
    • Boston, Massachusetts, United States, 02111
    • Boston, Massachusetts, United States, 02114-2696
    • Burlington, Massachusetts, United States, 01805
  • Michigan
    • Detroit, Michigan, United States, 48202-2689
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
    • Rochester, Minnesota, United States, 55905
  • Missouri
    • St Louis, Missouri, United States, 63110
  • New Jersey
    • Newark, New Jersey, United States, 07101-1709
  • New York
    • Hawthorne, New York, United States, 10532
    • New York, New York, United States, 10016
    • New York, New York, United States, 10032
    • New York, New York, United States, 10029
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
  • Ohio
    • Cleveland, Ohio, United States, 44195
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112-4481
  • Oregon
    • Portland, Oregon, United States, 97201-3098
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19141
  • Tennessee
    • Nashville, Tennessee, United States, 37232
  • Texas
    • Dallas, Texas, United States, 75246
    • Houston, Texas, United States, 77030
    • San Antonio, Texas, United States, 78284
  • Virginia
    • Richmond, Virginia, United States, 23298
  • Wisconsin
    • Madison, Wisconsin, United States, 53792

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients 18-74 years of age
• Single primary liver transplant from a deceased donor
• CellCept plus tacrolimus or cyclosporine from time of transplantation (within 72 hours)
• Patients with hepatitis C-positive status may be entered if they have had an intraoperative (back table) biopsy of the transplanted liver or will have a biopsy at the time of randomization. This is not required for patients negative for hepatitis C.

Exclusion Criteria:

• Liver allograft from a living donor or a split liver
• Multiple organ transplant
• Dialysis therapy for >14 days from transplantation to randomization
• History of malignancy in the last 5 years (except hepatoma or non-melanoma skin cancer)
• Previous sirolimus therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CellCept + CNI (tacrolimus or cyclosporine)	Drug: mycophenolate mofetil [CellCept]; 1-1.5 g orally or intravenously twice daily; Drug: Tacrolimus; As prescribed, for 12 months; Drug: Cyclosporine; As prescribed, for 12 months
Active Comparator: CellCept + sirolimus	Drug: mycophenolate mofetil [CellCept]; 1-1.5 g orally or intravenously twice daily; Drug: Sirolimus; 2-4 mg orally once daily for 9-11 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Glomerular Filtration Rate (GFR) at 12 Months Posttransplant	Mean percent change from baseline in estimated glomerular filtration rate (GFR) calculated by modification of diet in renal disease (MDRD)-6 variable equation at 12 months posttransplantation. MDRD-6 variables: serum creatinine, albumin and urea nitrogen, gender, age and ethnicity.	12 months posttransplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Glomerular Filtration Rate (GFR) at 6 Months Posttransplant	Mean percent change from baseline in estimated GFR calculated by modification of diet in renal disease (MDRD)-6 variable equation at 6 and 24 months posttransplantation. MDRD-6 variables: serum creatinine, albumin and urea nitrogen, gender, age and ethnicity.	6 months posttransplant
Change From Baseline in Glomerular Filtration Rate (GFR) at 24 Months Posttransplant	Mean percent change from baseline in estimated GFR calculated by modification of diet in renal disease (MDRD)-6 variable equation at 6 and 24 months posttransplantation. MDRD-6 variables: serum creatinine, albumin and urea nitrogen, gender, age and ethnicity.	24 months posttransplant
Change From Baseline in Creatinine Clearance	Mean percent change from baseline in calculated creatinine clearance (CL) at 6, 12, and 24 months posttransplantation	6, 12, and 24 months posttransplantation

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

Helpful Links

• Clinical Study Report Synopsis

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: June 30, 2005
• First Submitted That Met QC Criteria: July 11, 2005
• First Posted (Estimate): July 12, 2005

Study Record Updates

• Last Update Posted (Estimate): August 3, 2010
• Last Update Submitted That Met QC Criteria: July 30, 2010
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid; Sirolimus; Cyclosporine; Cyclosporins
• Other Study ID Numbers: ML18423