Back to resultsEnteric-coated Mycophenolate Sodium (EC-MPS) With Reduced-dose Tacrolimus Versus EC-MPS With Standard-dose Tacrolimus in Stable Kidney Transplant Recipients (OLYMPE)
Primary Purpose
Kidney Diseases
Status
Completed
Phase
Phase 3
Locations
Switzerland
Study Type
Interventional
Intervention
Enteric-coated mycophenolate sodium (EC-MPS)
Tacrolimus
Corticosteroids
Sponsored by
About this trial
This is an interventional treatment trial for Kidney Diseases focused on measuring Dose optimization, immune suppressive regimen, enteric-coated mycophenolate sodium, EC-MPS, renal transplantation, kidney, transplant, maintenance patients, Renal transplantation in maintenance
Eligibility Criteria
Inclusion Criteria: Primary or secondary kidney transplant Treatment with mycophenolic acid (MMF 1 g/d or EC-MPS 720 mg/d) and tacrolimus (trough concentration [C0] ≥ 5.5 ng/mL) Creatinine clearance ≥ 30 mL/min and < 60 mL/min and stable renal function Exclusion Criteria: Multi-organ recipients or previous transplant with any other organ different from kidney Biopsy proven acute rejection or treated acute rejection within the last 3 months. Prescription of mycophenolate mofetil 1 g/d or mycophenolate sodium 720 mg/d due to adverse event occurrence when higher doses were administered Other protocol-defined inclusion/exclusion criteria may apply.
Sites / Locations
- Novartis
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Standard dose EC-MPS
High EC-MPS
Arm Description
Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus dose (twice a day orally) adjusted to maintain the trough blood level (C0) contained between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
Patients received 1440 mg/day (720 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus dose (twice a day orally) tapered to reach a trough blood level target contained between 2 and 4.5 ng/mL within 15 days after randomization at the most. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
Outcomes
Primary Outcome Measures
Renal Function Assessed by Change in Estimated Glomerular Filtration Rate(eGFR)
Change in estimated glomerular filtration rate from baseline to Month 6 calculated by using abbreviated Modification of Diet in Renal Disease (MDRD) formula. Modification of Diet in Renal Disease (MDRD) formula is: GFR [mL/min/1.73m^2] = 186.3*(C^-1.154)*(A^-0.203)*G*R where -C is the serum concentration of creatinine [mg/dL], -A is patient age at sample collection date [years], -G=0.742 when gender is female, otherwise G=1, -R=1.21 when race is black, otherwise R=1.
Secondary Outcome Measures
Renal Function at 3 Months Assessed by Change in Estimated Glomerular Filtration Rate (eGFR)
Change in estimated glomerular filtration rate from baseline to Month 3 calculated by using abbreviated MDRD formula. Modification of Diet in Renal Disease (MDRD) formula is: GFR [mL/min/1.73m^2] = 186.3*(C^-1.154)*(A^-0.203)*G*R where -C is the serum concentration of creatinine [mg/dL], -A is patient age at sample collection date [years], -G=0.742 when gender is female, otherwise G=1, -R=1.21 when race is black, otherwise R=1.
Number of Participants With Treatment Failure Parameters (Biopsy-Proven Acute Rejection (BPAR), Graft Loss, Death, or Loss to Follow-up) at 6 Months
A biopsy-proven acute rejection (BPAR) is defined as a biopsy graded IA, IB, IIA, IIB, or III based on the Banff 1997 classification.The allograft was presumed lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis. If the patient went through a graft nephrectomy, then the day of nephrectomy was the day of graft loss.
Number of Participants With Graft and Patient Survivals at 6 Months
Graft survival was defined as the number of patients with no graft loss. The allograft was presumed lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis. If the patient went through a graft nephrectomy, then the day of nephrectomy was the day of graft loss. Patient survival was defined as the number of patients alive with or without a functioning graft.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00284934
Brief Title
Enteric-coated Mycophenolate Sodium (EC-MPS) With Reduced-dose Tacrolimus Versus EC-MPS With Standard-dose Tacrolimus in Stable Kidney Transplant Recipients
Acronym
OLYMPE
Official Title
A Multicenter, National, Open-label, Prospective, Randomized Study to Evaluate Efficacy and Tolerability of Enteric-coated Mycophenolate Sodium 1440 mg/Day With Tacrolimus Reduced Dose Versus Enteric-coated Mycophenolate Sodium 720 mg/Day With Tacrolimus Standard Dose, in Maintenance, Stable, Adult, Kidney Transplant Recipients
Study Type
Interventional
2. Study Status
Record Verification Date
March 2011
Overall Recruitment Status
Completed
Study Start Date
December 2005 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
June 2008 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Novartis
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study introduces a new optimization immunosuppressive regimen associating tacrolimus at a reduced dose and enteric-coated mycophenolate sodium at an increased dose in order to slow down renal function worsening and to prevent the progression of chronic allograft nephropathy, while maintaining the same efficacy, in maintenance renal transplant recipients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Diseases
Keywords
Dose optimization, immune suppressive regimen, enteric-coated mycophenolate sodium, EC-MPS, renal transplantation, kidney, transplant, maintenance patients, Renal transplantation in maintenance
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
94 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Standard dose EC-MPS
Arm Type
Active Comparator
Arm Description
Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus dose (twice a day orally) adjusted to maintain the trough blood level (C0) contained between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
Arm Title
High EC-MPS
Arm Type
Experimental
Arm Description
Patients received 1440 mg/day (720 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus dose (twice a day orally) tapered to reach a trough blood level target contained between 2 and 4.5 ng/mL within 15 days after randomization at the most. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day.
Intervention Type
Drug
Intervention Name(s)
Enteric-coated mycophenolate sodium (EC-MPS)
Other Intervention Name(s)
Myfortic
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
Prograf
Intervention Type
Drug
Intervention Name(s)
Corticosteroids
Other Intervention Name(s)
Prednisone
Intervention Description
At a dose of at least 5 mg/day.
Primary Outcome Measure Information:
Title
Renal Function Assessed by Change in Estimated Glomerular Filtration Rate(eGFR)
Description
Change in estimated glomerular filtration rate from baseline to Month 6 calculated by using abbreviated Modification of Diet in Renal Disease (MDRD) formula. Modification of Diet in Renal Disease (MDRD) formula is: GFR [mL/min/1.73m^2] = 186.3*(C^-1.154)*(A^-0.203)*G*R where -C is the serum concentration of creatinine [mg/dL], -A is patient age at sample collection date [years], -G=0.742 when gender is female, otherwise G=1, -R=1.21 when race is black, otherwise R=1.
Time Frame
Baseline and Month 6
Secondary Outcome Measure Information:
Title
Renal Function at 3 Months Assessed by Change in Estimated Glomerular Filtration Rate (eGFR)
Description
Change in estimated glomerular filtration rate from baseline to Month 3 calculated by using abbreviated MDRD formula. Modification of Diet in Renal Disease (MDRD) formula is: GFR [mL/min/1.73m^2] = 186.3*(C^-1.154)*(A^-0.203)*G*R where -C is the serum concentration of creatinine [mg/dL], -A is patient age at sample collection date [years], -G=0.742 when gender is female, otherwise G=1, -R=1.21 when race is black, otherwise R=1.
Time Frame
Baseline and 3 months
Title
Number of Participants With Treatment Failure Parameters (Biopsy-Proven Acute Rejection (BPAR), Graft Loss, Death, or Loss to Follow-up) at 6 Months
Description
A biopsy-proven acute rejection (BPAR) is defined as a biopsy graded IA, IB, IIA, IIB, or III based on the Banff 1997 classification.The allograft was presumed lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis. If the patient went through a graft nephrectomy, then the day of nephrectomy was the day of graft loss.
Time Frame
6 months
Title
Number of Participants With Graft and Patient Survivals at 6 Months
Description
Graft survival was defined as the number of patients with no graft loss. The allograft was presumed lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis. If the patient went through a graft nephrectomy, then the day of nephrectomy was the day of graft loss. Patient survival was defined as the number of patients alive with or without a functioning graft.
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Primary or secondary kidney transplant
Treatment with mycophenolic acid (MMF 1 g/d or EC-MPS 720 mg/d) and tacrolimus (trough concentration [C0] ≥ 5.5 ng/mL)
Creatinine clearance ≥ 30 mL/min and < 60 mL/min and stable renal function
Exclusion Criteria:
Multi-organ recipients or previous transplant with any other organ different from kidney
Biopsy proven acute rejection or treated acute rejection within the last 3 months.
Prescription of mycophenolate mofetil 1 g/d or mycophenolate sodium 720 mg/d due to adverse event occurrence when higher doses were administered
Other protocol-defined inclusion/exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis
Organizational Affiliation
Novartis
Official's Role
Study Director
Facility Information:
Facility Name
Novartis
City
Basel
Country
Switzerland
12. IPD Sharing Statement
Citations:
PubMed Identifier
22257543
Citation
Kamar N, Rostaing L, Cassuto E, Villemain F, Moal MC, Ladriere M, Barrou B, Ducloux D, Chaouche K, Quere S, Di Giambattista F, Be F. A multicenter, randomized trial of increased mycophenolic acid dose using enteric-coated mycophenolate sodium with reduced tacrolimus exposure in maintenance kidney transplant recipients. Clin Nephrol. 2012 Feb;77(2):126-36. doi: 10.5414/CN107227.
Results Reference
derived
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Enteric-coated Mycophenolate Sodium (EC-MPS) With Reduced-dose Tacrolimus Versus EC-MPS With Standard-dose Tacrolimus in Stable Kidney Transplant Recipients
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