Comparative Study of Modified Release (MR) Tacrolimus/Mycophenolate Mofetil (MMF) in de Novo Kidney Transplant Recipients
A Phase III, Randomized, Open-Label, Comparative, Multi-Center Study to Assess the Safety and Efficacy of Prograf (Tacrolimus)/MMF, Modified Release (MR) Tacrolimus/MMF and Neoral (Cyclosporine)/MMF in de Novo Kidney Transplant Recipients
1 other identifier
interventional
668
3 countries
57
Brief Summary
The purpose of this study is to compare the safety and efficacy of tacrolimus/mycophenolate mofetil (MMF), cyclosporine/MMF and tacrolimus modified release/MMF in de novo kidney transplant recipients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jun 2003
Longer than P75 for phase_3
57 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2003
CompletedFirst Submitted
Initial submission to the registry
July 10, 2003
CompletedFirst Posted
Study publicly available on registry
July 14, 2003
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2005
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2009
CompletedResults Posted
Study results publicly available
September 26, 2013
CompletedDecember 5, 2013
November 1, 2013
1.8 years
July 10, 2003
July 25, 2013
November 12, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With Efficacy Failure
Efficacy failure is defined as any participant who died, experienced a graft failure (permanent return to dialysis \[\> 30 days\] or retransplant), had a biopsy-confirmed (Banff Grade ≥ I) acute rejection (BCAR), or was lost to follow-up. Biopsies were graded according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel.
one year
Secondary Outcomes (14)
Patient Survival at One Year
One year
Graft Survival at One Year
One year
Percentage of Participants With Biopsy Confirmed Acute Rejection at 6 and 12 Months
Six months and 12 months
Time to First Biopsy-confirmed Acute Rejection Episode
one year
Number of Participants Requiring Anti-lymphocyte Antibody Therapy for Treatment of Rejection
one year
- +9 more secondary outcomes
Study Arms (3)
Tacrolimus
EXPERIMENTALParticipants received a first dose of tacrolimus between 0.075 and 0.10 mg/kg twice daily, orally prior to or within 48 hours of the completion of the transplant procedure, and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
Tacrolimus Modified Release
ACTIVE COMPARATORParticipants received a first dose of tacrolimus modified release between 0.15 and 0.20 mg/kg/day, given as a single oral dose in the morning, prior to or within 48 hours following the completion of the transplant procedure, and subsequently as once daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
Cyclosporine
ACTIVE COMPARATORParticipants received a first dose of cyclosporine between 4 to 5 mg/kg orally prior to or within 48 hours following the completion of the transplant procedure and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events. Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
Interventions
The target range for whole blood tacrolimus trough concentrations was 7 to 16 ng/mL for days 0 through 90, and 5 to 15 ng/mL thereafter.
The target range for whole blood tacrolimus trough concentrations was the recommended trough concentration range for Prograf: 7 to 16 ng/mL for days 0 through 90 and 5 to 15 ng/mL thereafter.
The target range for whole blood cyclosporine trough concentrations was 125 to 400 ng/mL for days 0 through 90, and 100 to 300 ng/mL thereafter.
Oral
Eligibility Criteria
You may qualify if:
- Recipient of a primary or retransplanted non-human leukocyte antigen (HLA)-identical living or non-HLA-identical cadaveric kidney transplant
- Age greater or equal to 12 years
You may not qualify if:
- Recipient or donor is known seropositive for human immunodeficiency virus (HIV)
- Has current malignancy or history of malignancy
- Has significant liver disease
- Has uncontrolled concomitant infection or any other unstable medical condition
- Is receiving everolimus or enteric coated mycophenolic acid at any time during the study
- Received kidney with a cold ischemia time of equal or more than 36 hours
- Received kidney transplant from a cadaveric donor equal or more than 60 years of age
- Received intravenous immunoglobulin (IVIG) therapy prior to randomization
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (57)
Unknown Facility
Birmingham, Alabama, 35294, United States
Unknown Facility
Mobile, Alabama, 36617, United States
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Loma Linda, California, 92354, United States
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Los Angeles, California, 90033, United States
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Los Angeles, California, 90057, United States
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Los Angeles, California, 90058, United States
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Los Angeles, California, 90095-7306, United States
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Palo Alto, California, 94304, United States
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San Diego, California, 92103, United States
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San Diego, California, 92123, United States
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San Francisco, California, 94115, United States
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Denver, Colorado, 80262, United States
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Washington D.C., District of Columbia, 20010, United States
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Gainesville, Florida, 32610-0224, United States
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Jacksonville, Florida, 32216, United States
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Augusta, Georgia, 30912, United States
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Chicago, Illinois, 60612, United States
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Chicago, Illinois, 60637, United States
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Indianapolis, Indiana, 46202, United States
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Lexington, Kentucky, 40536, United States
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New Orleans, Louisiana, 70112, United States
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New Orleans, Louisiana, 70121, United States
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Boston, Massachusetts, 02214, United States
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Ann Arbor, Michigan, 48109-0364, United States
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Detroit, Michigan, 48202, United States
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Livingston, New Jersey, 07039, United States
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New Brunswick, New Jersey, 08901, United States
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Albany, New York, 12208, United States
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Buffalo, New York, 14203, United States
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New York, New York, 10029, United States
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Valhalla, New York, 10595, United States
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Chapel Hill, North Carolina, 27599-7211, United States
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Durham, North Carolina, 27710, United States
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Cincinnati, Ohio, 45267, United States
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Portland, Oregon, 97210, United States
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Portland, Oregon, 97239-2940, United States
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Harrisburg, Pennsylvania, 17104, United States
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Philadelphia, Pennsylvania, 19104, United States
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Philadelphia, Pennsylvania, 19107, United States
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Nashville, Tennessee, 37212-4750, United States
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Dallas, Texas, 75235, United States
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Dallas, Texas, 75246, United States
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Houston, Texas, 77030, United States
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San Antonio, Texas, 78229-3900, United States
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Salt Lake City, Utah, 84132, United States
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Fairfax, Virginia, 22031, United States
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Madison, Wisconsin, 53792-7375, United States
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Milwaukee, Wisconsin, 53226, United States
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Porto Alegre, 90240-520, Brazil
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Rio de Janeiro, 21041-003, Brazil
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São Paulo, 04013-043, Brazil
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São Paulo, 04038-002, Brazil
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São Paulo, 05465-040, Brazil
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Edmonton, Alberta, Canada
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Vancouver, British Columbia, Canada
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Toronto, Ontario, Canada
Unknown Facility
Montreal, Quebec, Canada
Related Publications (1)
Silva HT Jr, Yang HC, Abouljoud M, Kuo PC, Wisemandle K, Bhattacharya P, Dhadda S, Holman J, Fitzsimmons W, First MR. One-year results with extended-release tacrolimus/MMF, tacrolimus/MMF and cyclosporine/MMF in de novo kidney transplant recipients. Am J Transplant. 2007 Mar;7(3):595-608. doi: 10.1111/j.1600-6143.2007.01661.x. Epub 2007 Jan 11.
PMID: 17217442BACKGROUND
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Company makes no warranties or representations of any kind as to the posting, expressed or implied, including warranties of merchantability and fitness for a particular purpose, and shall not be liable for any damages.
Results Point of Contact
- Title
- Vice President, Therapeutic Area Head, Transplantation
- Organization
- Astellas Pharma Global Development, Inc.
Study Officials
- STUDY DIRECTOR
Use Central Contact
Astellas Pharma Global Development
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 10, 2003
First Posted
July 14, 2003
Study Start
June 1, 2003
Primary Completion
March 1, 2005
Study Completion
March 1, 2009
Last Updated
December 5, 2013
Results First Posted
September 26, 2013
Record last verified: 2013-11