Evaluate Efficacy Study of Combination Therapy of Everolimus and Low Dose Tacrolimus in Renal Allograft Recipients

Phase 4UnknownNCT02036554

Seoul St. Mary's Hospital234 enrolled

Overview

To evaluate prevention effect of combination therapy of Everolimus and low-dose Tacrolimus in comparison with standard-dose Tacrolimus therapy with Mycophenolic acid on the New Onset Diabetes Mellitus after transplantation in the renal allograft recipients

An open-label, randomized, multi-center, comparative parallel study to evaluate prevention effect of combination therapy of Everolimus and low-dose Tacrolimus in comparison with standard-dose Tacrolimus therapy with Mycophenolic acid on the New Onset Diabetes Mellitus after transplantation in the renal allograft recipients: PROTECT study

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

234

Conditions

Kidney; Complications, Allograft

Interventions

EverolimusDRUG

Decrease the level of Tacrolimus and add on Everolimus instead of Mycophenolic acid which is standard treatment.

TacrolimusDRUG

Decrease the level of Tacrolimus and add on Everolimus instead of Mycophenolic acid which is standard treatment.

Mycophenolic acidDRUG

Decrease the level of Tacrolimus and add on Everolimus instead of Mycophenolic acid which is standard treatment.

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥ 20 year old 2. At least 3 months after kidney transplantation 3. Subject who is using Tacrolimus ± purine synthesis inhibitor + steroid without change within the past 3 months (except the dosage) 4. MDRD eGFR ≥ 50 mL/min or serum creatinine \< 2.0mg/dL within the past 3 months in the 6months after kidney transplantation 5. Rate of change of serum creatinine \< +30% within the past 3 months in the 6months after kidney transplantation (if serum creatinine decreased, without rate of change is inclusion possible. if serum creatinine result was normal,regardless of the rate of change is able to register.) 6. Urine protein/creatinine ratio \< 1g/g Cr (spot urine) Subject who is not applicable to the diagnostic criteria NODAT on 7. the baseline in the 6months after kidney transplantation 8. Subjects who agree with written informed consent Exclusion Criteria: 1. Subjects who received combined non-renal transplantation 2. Subject who received re-transplantation 3. ABO blood group incompatible(when anti-ABO Antibody titer \<1:128 is inclusion possible.) 4. Sensitized patients before transplantation * Pretransplant or peak PRA titer \> 50% * Pretransplant T cell cytotoxicity crossmatch (+) 5. HLA-identical living related donor 6. Subject who has diabetes mellitus / NODAT before transplantation 7. Subject who has suffered acute rejection episode within the past 3 months in the 6months after kidney transplantation 8. Subject with hypersensitivity to everolimus 9. Subject who should continue nephrotoxic drug until enrollment (Aminoglycoside, amphotericin B, cisplatin) 10. Subject with GI disorder that might interfere with the ability to absorb oral medication. (eg, gastrectomy or insufficiently treated diabetic gastroenteropathy) 11. Subjects with active peptic ulcer 12. HIV, HBsAg, or HCV Ab tests (+) 13. Abnormal liver function test (AST or ALT or total bilirubin\> upper normal limit x3) 14. ANC \<1.5\*109/L or WBC \<2.5\*109/L or platelet \<75\*109/L 15. Treatment with an investigational drug within 30 days preceding the first dose of trial medication 16. Women who are either pregnant, lactating, planning to become pregnant in the next 12 months. 17. Subjects with history of cancer(except successfully treated), localized nonmelanocytic skin cancer, PTLD(Post-transplant lymphoproliferative disorder) 18. Subjects with clinically significant infections within the past 4 weeks in the 6months after kidney transplantation 19. Subjects who took major surgery within the past 4 weeks in the 6months after kidney transplantation

Locations (1)

division of nephrology;Seoul St Mary's Hospital

Seoul, South Korea

RECRUITING

Outcomes

Primary Outcomes

Change from Baseline in Development of NODAT (Fasting glucose ≥ 126 mg/dL, Random glucose ≥ 200 mg/dL) at 12 months

Time frame: 0 to 12 month

Secondary Outcomes

Insulin resistance by HOMA-IR

Change from Baseline(V2) in Insulin resistance by HOMA-IR at 12months(V6)

Time frame: 0 to 12 months

Insulin secretion by HOMA-beta

Change from Baseline(V2) in insulin secretion by HOMA-beta at 12 months(V6)

Time frame: 0 to 12 months

OGTT (Fasting and PP2hr)

Change from baseline in OGTT (Fasting and PP2hr) at 12 months(V6)

Time frame: 0 to 12 months

Needs for anti-diabetic medication or insulin

Needs for anti-diabetic medication or insulin at Baseline(V2)

Time frame: at Baseline(V2)

Needs for anti-diabetic medication or insulin at 3 month(V3)

Time frame: at 3 month(V3)

Needs for anti-diabetic medication or insulin at 6 month(V4)

Time frame: at 6 month(V4)

Data from ClinicalTrials.gov

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Needs for anti-diabetic medication or insulin at 9 month(V5)

Time frame: at 9 month(V5)

Needs for anti-diabetic medication or insulin at 12 month(V6)

Time frame: at 12 month(V6)

Creatinine clearance (MDRD eGFR) at Baseline(V2)

Time frame: at Baseline(V2)

Creatinine clearance (MDRD eGFR) at 3 month(V3)

Time frame: at 3 month(V3)

Creatinine clearance (MDRD eGFR) at 6 month(V4)

Time frame: at 6 month(V4)

Creatinine clearance (MDRD eGFR) at 9 month(V5)

Time frame: at 9 month(V5)

Creatinine clearance (MDRD eGFR) at 12 month(V6)

Time frame: at 12 month(V6)

12 month graft survival

After date of randomization, evaluate graft survival rate at 12 months(V6)

Time frame: at 12 months(V6)

12 month patient survival rate

After date of randomization, evaluate patient survival rate at 12 months(V6)

Time frame: at 12 months(V6)

Change from baseline in Microalbuminuria(MAU) at 12 months

Time frame: at 12 months(V6)

Proportion of patients with significant proteinuria greater than 1g/gCr at Baseline(V2)

Time frame: at Baseline(V2)

Proportion of patients with significant proteinuria greater than 1g/gCr at 3 month(V3)

Time frame: at 3 month(V3)

Proportion of patients with significant proteinuria greater than 1g/gCr at 6 month(V4)

Time frame: at 6 month(V4)

Proportion of patients with significant proteinuria greater than 1g/gCr at 9 month(V5)

Time frame: at 9 month(V5)

Proportion of patients with significant proteinuria greater than 1g/gCr at 12 month(V6)

Time frame: at 12 month(V6)

Number of episode of biopsy proven acute rejection (BPAR)

Cumulative incidence rate of Biopsy Proven Acute Rejection(BPAR) at 12months(V6) after date of randomization.

Time frame: at 12 month(V6)

Number of hospitalization of any cause (except admission for protocol biopsy) at Baseline(V2)

Time frame: at Baseline(V2)

Number of hospitalization of any cause (except admission for protocol biopsy) at 3 month(V3)

Time frame: at 3 month(V3)

Number of hospitalization of any cause (except admission for protocol biopsy) at 6 month(V4)

Time frame: at 6 month(V4)

Number of hospitalization of any cause (except admission for protocol biopsy) at 9 month(V5)

Time frame: at 9 month(V5)

Number of hospitalization of any cause (except admission for protocol biopsy) at 12 month(V6)

Time frame: at 12 month(V6)

Number of opportunistic infections (BKVN) at Baseline(V2)

Time frame: at Baseline(V2)

Number of opportunistic infections (BKVN) at 12month(V6)

Time frame: at 12 month(V6)

Prevalence of NODAT at Baseline(V2)

Time frame: at Baseline(V2)

Prevalence of NODAT at 3 month(V3)

Time frame: at 3 month(V3)

Prevalence of NODAT at 6 month(V4)

Time frame: at 6 month(V4)

Prevalence of NODAT at 9 month (V5)

Time frame: at 9 month (V5)

Prevalence of NODAT at 12 month(V6)

Time frame: at 12 month(V6)