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

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

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:

1. estimated GFR (MDRD equation) 12 months after randomization
2. estimated GFR change from randomization to end of the study (calculated by MDRD equation and Nankivell equation)

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: routine dose tacrolimus and less myfortic; Drug: reduced dose tacrolimus and conventional myfortic

• Study Type: Interventional
• Enrollment (Actual): 350
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Asan Medical Center
    • Seoul, Asan Medical Center, Korea, Republic of, 138-736
      • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

<Inclusion criteria>

1. The patients between the ages of 20 and 75 years who received kidney transplantation one to five years prior to the study.
2. Taking tacrolimus and corticosteroid, with or without additional purine synthesis inhibitor within the recent 3 months
3. Patients with serum creatinine (sCr) level ≤ 2.0 mg/dL and variation of sCr < 30% for recent 3 months
4. Patients with urine proteinuria/creatinine ratio (PCR) ≤ 1 g/g, or 24 hour urine protein ≤ 1g/day for recent 3 months
5. Patients who provided informed consent.

<Exclusion criteria>

1. Patients who received combined non-renal transplantation, multiple kidney transplantation or re-transplantation
2. Patients whose graft from non-heart beating cadaveric donor
3. graft from HLA-identical living related donor
4. ABO blood group incompatible donor or HLA desensitized recipients
5. Patients with hypersensitivity history to mycophenolate sodium, mycophenolate acid, or mycophenolate mofetil, or to any other excipients
6. Patients with hypoxanthin e-guanine phosphoribosyl-transferase such as Lesch-Nyhan syndrome and Kelley-Seegmiller syndrome
7. Patients with history of disease which could affect absorption of study medication (e.g. diabetic gastropathy, previous gastrectomy)
8. Patients with positive serologic test results, in recipient or donor, for human immunodeficiency virus, hepatitis B or C virus
9. 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)
10. Patients with history of cancer within 5 years, except for successfully treated localized non-melanocytic skin cancer
11. Patients who were either pregnant, lactating, planning to become pregnant in the next 12 months
12. Patients who taken medicine from other trial within 30 days.

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
Active Comparator: routine dose tacrolimus and less myfortic	Drug: routine dose tacrolimus and less myfortic; 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
Experimental: reduced dose tacrolimus and conventional myfortic	Drug: reduced dose tacrolimus and conventional myfortic; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Collaborators: Samsung Medical Center; Seoul National University Hospital
• Investigators: Principal Investigator: Su-Kil Park, MD,PhD, Asan Medical Center

Publications and helpful links

General Publications

• Park S, Kim YS, Lee J, Huh W, Yang CW, Kim YL, Kim YH, Kim JK, Oh CK, Park SK. Reduced Tacrolimus Trough Level Is Reflected by Estimated Glomerular Filtration Rate (eGFR) Changes in Stable Renal Transplantation Recipients: Results of the OPTIMUM Phase 3 Randomized Controlled Study. Ann Transplant. 2018 Jun 12;23:401-411. doi: 10.12659/AOT.909036.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2010
• Primary Completion (Actual): October 30, 2016
• Study Completion (Actual): November 30, 2016

Study Registration Dates

• First Submitted: July 6, 2010
• First Submitted That Met QC Criteria: July 8, 2010
• First Posted (Estimate): July 9, 2010

Study Record Updates

• Last Update Posted (Actual): March 14, 2017
• Last Update Submitted That Met QC Criteria: March 12, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: immunosuppression control in kidney transplantation
• 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; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid
• Other Study ID Numbers: CERL080AKR07T (Other Grant/Funding Number: NORVATIS)