Treatment of the optImuM Dose of calcineUrin Inhibitor and Mycophenolate Sodium in Kidney Recipients

Study Overview
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Brief Summary
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To clarify that tacrolimus-sparing regimen with minimal tacrolimus dose together with mycophenolate sodium dose increment will preserve renal allograft function without rising adverse effects Primary endpoints: estimated GFR (MDRD equation) 12 months after randomization estimated GFR change from randomization to end of the study (calculated by MDRD equation and Nankivell equation)

Official Title
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Organ Function Preservation by the Combination Treatment of the optImuM Dose of calcineUrin Inhibitor and Mycophenolate Sodium in Kidney Recipients: OPTIMUM Study

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: routine dose tacrolimus and less myfortic
* Drug: reduced dose tacrolimus and conventional myfortic


Participation Criteria
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Eligibility Criteria
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<Inclusion criteria> The patients between the ages of 20 and 75 years who received kidney transplantation one to five years prior to the study. Taking tacrolimus and corticosteroid, with or without additional purine synthesis inhibitor within the recent 3 months Patients with serum creatinine (sCr) level ≤ 2.0 mg/dL and variation of sCr < 30% for recent 3 months Patients with urine proteinuria/creatinine ratio (PCR) ≤ 1 g/g, or 24 hour urine protein ≤ 1g/day for recent 3 months Patients who provided informed consent. <Exclusion criteria> Patients who received combined non-renal transplantation, multiple kidney transplantation or re-transplantation Patients whose graft from non-heart beating cadaveric donor graft from HLA-identical living related donor ABO blood group incompatible donor or HLA desensitized recipients Patients with hypersensitivity history to mycophenolate sodium, mycophenolate acid, or mycophenolate mofetil, or to any other excipients Patients with hypoxanthin e-guanine phosphoribosyl-transferase such as Lesch-Nyhan syndrome and Kelley-Seegmiller syndrome Patients with history of disease which could affect absorption of study medication (e.g. diabetic gastropathy, previous gastrectomy) Patients with positive serologic test results, in recipient or donor, for human immunodeficiency virus, hepatitis B or C virus Patients with liver function test abnormality (alanine aminotransferase, aspartate aminotransferase, or total bilirubin > 3 times from upper normal limit), neutropenia (absolute neutrophil count < 1,500/uL or white blood cell count < 2,500/uL), or thrombocytopenia (platelet < 75,000) Patients with history of cancer within 5 years, except for successfully treated localized non-melanocytic skin cancer Patients who were either pregnant, lactating, planning to become pregnant in the next 12 months Patients who taken medicine from other trial within 30 days.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: routine dose tacrolimus and less myfortic<br> | Drug: routine dose tacrolimus and less myfortic<br>* oral regular dose of tacrolimus + less dose of myfortic trough level of tacrolimus will be 5-10 ng/mL and oral myfortic dose will be 180-360 mg twice a day<br>|
| Experimental: reduced dose tacrolimus and conventional myfortic<br> | Drug: reduced dose tacrolimus and conventional myfortic<br>* low dose of tacrolimus + maximum dose of myfortic target trough level of tacrolimus should be reduced to 2-5 ng/mL for 3 months after randomization and oral MPS dose increased to 540-720mg twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| estimated GFR (MDRD equation)12 months after randomization |  | 12 months after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urine protein excretion | 24hr urine collection or urine protein/creatinine ratio | 12 months after randomization | 
| graft survival | 12 month graft survival | 12 month after randomization | 
| follow-up loss | frequency of follow-up loss | From randomization to 12 months after randomization | 
| Allograft biopsy | number of performed allograft biopsy performed | From randomization to 12 months after randomization | 
| Treated or biopsy proven acute rejection |  | From randomization to 12 months after randomization | 
| estimated GFR change from randomization to end of the study | calculated by MDRD equation and Nankivell equation | 12 months after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunosuppression control in kidney transplantation