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

An Open Label, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of Early Calcineurin Inhibitor Withdrawal in Recipients of Primary Renal Allografts Maintained Long-term on Mycophenolate Mofetil (MMF) (CellCept®) and Sirolimus (Rapamune®)

This 2-arm study recruited kidney transplant patients who were receiving standard care of calcineurin inhibitors (CNIs, tacrolimus or cyclosporine), CellCept (1.0-1.5 g twice daily) and corticosteroids. They were either randomized to continue this regimen, or CNI therapy was discontinued and replaced by sirolimus therapy (in combination with CellCept and corticosteroids). The effect of these 2 regimens on efficacy, safety and kidney function was evaluated. The anticipated time on study treatment was 1-2 years, and the target sample size was 100-500 individuals.

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: Corticosteroids; Drug: mycophenolate mofetil [CellCept]; Drug: Sirolimus; Drug: Calcineurin inhibitors

• Study Type: Interventional
• Enrollment (Actual): 305
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Bakersfield, California, United States, 93309
    • Los Angeles, California, United States, 90033
    • Los Angeles, California, United States, 90057
    • Palo Alto, California, United States, 94304-1509
    • Riverside, California, United States, 92501
    • San Diego, California, United States, 92123
    • San Francisco, California, United States, 94115
  • Colorado
    • Denver, Colorado, United States, 80262
  • Connecticut
    • Hartford, Connecticut, United States, 06106-3316
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2975
  • Georgia
    • Atlanta, Georgia, United States, 30322
  • Illinois
    • Maywood, Illinois, United States, 60153
  • Indiana
    • Indianapolis, Indiana, United States, 46202
    • Indianapolis, Indiana, United States, 46202-5124
  • Iowa
    • Iowa City, Iowa, United States, 52242
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0293
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
  • Maryland
    • Baltimore, Maryland, United States, 21201
  • Massachusetts
    • Boston, Massachusetts, United States, 02114-2696
  • Michigan
    • Detroit, Michigan, United States, 48202-2689
  • New Jersey
    • Camden, New Jersey, United States, 08103
    • Livingston, New Jersey, United States, 07039
  • New York
    • New York, New York, United States, 10032
    • New York, New York, United States, 10029
  • North Carolina
    • Durham, North Carolina, United States, 27710
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0558
  • Oregon
    • Portland, Oregon, United States, 97201
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
  • South Carolina
    • Charleston, South Carolina, United States, 29425
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
  • Tennessee
    • Memphis, Tennessee, United States, 38104
    • Nashville, Tennessee, United States, 37232
  • Texas
    • Dallas, Texas, United States, 75246
    • Galveston, Texas, United States, 77555
    • San Antonio, Texas, United States, 78284
  • Virginia
    • Charlottesville, Virginia, United States, 22908

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients 18-75 years of age
• Kidney transplant 30-180 days post-transplantation
• Receipt of cyclosporine or tacrolimus, CellCept, and corticosteroids for greater than 14 days prior to study entry
• No known contraindications to sirolimus

Exclusion Criteria:

• Multiple organ transplant recipients or secondary kidney transplant recipients
• Corticosteroid-resistant rejection episode within 90 days prior to study entry or corticosteroid-sensitive rejection episode within 30 days prior to study entry
• More than 1 biopsy-proven episode of acute rejection prior to study entry
• Treated with sirolimus before the study
• Organ transplant or expected organ transplant, other than kidney
• History of malignancy in the last 5 years (except successfully treated localized non-melanotic skin cancer)

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: 1	Drug: Corticosteroids; As prescribed; Drug: mycophenolate mofetil [CellCept]; 1.0-1.5 g oral dose twice daily; Drug: Sirolimus; As prescribed
Active Comparator: 2	Drug: Corticosteroids; As prescribed; Drug: mycophenolate mofetil [CellCept]; 1.0-1.5 g oral dose twice daily; Drug: Calcineurin inhibitors; As prescribed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change in Glomerular Filtration Rate From Baseline to Month 12	The primary efficacy endpoint was mean percent change in renal function from baseline to 12 months postrandomization, as measured by Glomerular Filtration Rate utilizing renal clearance of cold iothalamate. percent change= [(Glomerular Filtration Rate at Month 12-Glomerular Filtration Rate at baseline)/Glomerular Filtration Rate at baseline]*100 percent.	baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change in Glomerular Filtration Rate From Baseline to Month 24	A secondary efficacy endpoint was mean percent change in renal function from baseline to 24 months postrandomization, as measured by Glomerular Filtration Rate utilizing renal clearance of cold iothalamate. percent change= [(Glomerular Filtration Rate at Month 24-Glomerular Filtration Rate at baseline)/Glomerular Filtration Rate at baseline]*100 percent.	Baseline to 24 months
Mean Percent Change in Serum Creatinine From Baseline to Months 6, 12, and 24	Renal allograft function determined by mean percent change from baseline in serum creatinine by treatment group at 6, 12, and 24 months postrandomization. percent change= [(serum creatinine at Month t-serum creatinine at baseline)/serum creatinine at baseline]*100 percent, where t=6, 12, and 24 months postrandomization.	baseline, 6, 12, and 24 months
Mean Percent Change in Calculated Creatinine Clearance From Baseline to Months 6, 12, and 24	Renal allograft function determined by mean percent change from baseline in calculated creatinine clearance (Cockroft and Gault method) by treatment group at 6, 12, and 24 months postrandomization. percent change= [(calculated creatinine clearance at Month t - calculated creatinine clearance at baseline)/calculated creatinine clearance at baseline]*100 percent, where t=6, 12, and 24 months postrandomization	baseline 6, 12, and 24 months
Mean Percent Change in Calculated Glomerular Filtration Rate From Baseline to Months 6, 12, and 24 (Nankivell Equation)	Renal allograft function determined by mean percent change from baseline in calculated Glomerular Filtration Rate (Nankivell equation) by treatment group at 6, 12, and 24 months postrandomization. percent change= [(calculated Glomerular Filtration Rate at Month t - calculated Glomerular Filtration Rate at baseline)/calculated Glomerular Filtration Rate at baseline]*100 percent, where t=6, 12, and 24 months postrandomization.	baseline, 6, 12, and 24 months

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, 2003
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: July 15, 2005
• First Submitted That Met QC Criteria: July 15, 2005
• First Posted (Estimate): July 21, 2005

Study Record Updates

• Last Update Posted (Estimate): April 15, 2011
• Last Update Submitted That Met QC Criteria: April 13, 2011
• Last Verified: April 1, 2011

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; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid; Sirolimus; Calcineurin Inhibitors
• Other Study ID Numbers: ML17140