Evaluate Efficacy Study of Combination Therapy of Everolimus and Low Dose Tacrolimus in Renal Allograft Recipients
- Conditions
- Kidney; Complications, Allograft
- Interventions
- Registration Number
- NCT02036554
- Lead Sponsor
- Seoul St. Mary's Hospital
- Brief Summary
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
- Detailed Description
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
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 234
- Age ≥ 20 year old
- At least 3 months after kidney transplantation
- Subject who is using Tacrolimus ± purine synthesis inhibitor + steroid without change within the past 3 months (except the dosage)
- MDRD eGFR ≥ 50 mL/min or serum creatinine < 2.0mg/dL within the past 3 months in the 6months after kidney transplantation
- 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.)
- Urine protein/creatinine ratio < 1g/g Cr (spot urine) Subject who is not applicable to the diagnostic criteria NODAT on
- the baseline in the 6months after kidney transplantation
- Subjects who agree with written informed consent
-
Subjects who received combined non-renal transplantation
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Subject who received re-transplantation
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ABO blood group incompatible(when anti-ABO Antibody titer <1:128 is inclusion possible.)
-
Sensitized patients before transplantation
- Pretransplant or peak PRA titer > 50%
- Pretransplant T cell cytotoxicity crossmatch (+)
-
HLA-identical living related donor
-
Subject who has diabetes mellitus / NODAT before transplantation
-
Subject who has suffered acute rejection episode within the past 3 months in the 6months after kidney transplantation
-
Subject with hypersensitivity to everolimus
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Subject who should continue nephrotoxic drug until enrollment (Aminoglycoside, amphotericin B, cisplatin)
-
Subject with GI disorder that might interfere with the ability to absorb oral medication. (eg, gastrectomy or insufficiently treated diabetic gastroenteropathy)
-
Subjects with active peptic ulcer
-
HIV, HBsAg, or HCV Ab tests (+)
-
Abnormal liver function test (AST or ALT or total bilirubin> upper normal limit x3)
-
ANC <1.5*109/L or WBC <2.5*109/L or platelet <75*109/L
-
Treatment with an investigational drug within 30 days preceding the first dose of trial medication
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Women who are either pregnant, lactating, planning to become pregnant in the next 12 months.
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Subjects with history of cancer(except successfully treated), localized nonmelanocytic skin cancer, PTLD(Post-transplant lymphoproliferative disorder)
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Subjects with clinically significant infections within the past 4 weeks in the 6months after kidney transplantation
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Subjects who took major surgery within the past 4 weeks in the 6months after kidney transplantation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tacrolimus plus Everolimus Everolimus Low dose Tacrolimus + Everolimus Tacrolimus plus Everolimus Tacrolimus Low dose Tacrolimus + Everolimus Tacrolimus plus Mycophenolic acid Tacrolimus standard dose Tacrolimus + Mycophenolic acid Tacrolimus plus Mycophenolic acid Mycophenolic acid standard dose Tacrolimus + Mycophenolic acid
- Primary Outcome Measures
Name Time Method Change from Baseline in Development of NODAT (Fasting glucose ≥ 126 mg/dL, Random glucose ≥ 200 mg/dL) at 12 months 0 to 12 month 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 at 12 months after date of randomization.
- Secondary Outcome Measures
Name Time Method Number of hospitalization of any cause (except admission for protocol biopsy) at 12 month(V6) at 12 month(V6) Number of hospitalization of any cause (except admission for protocol biopsy) at 12 month(V6)
Needs for anti-diabetic medication or insulin at 9 month(V5) at 9 month(V5) Needs for anti-diabetic medication or insulin at 9 month(V5)
Creatinine clearance (MDRD eGFR) at Baseline(V2) at Baseline(V2) Creatinine clearance (MDRD eGFR) at Baseline(V2)
Insulin secretion by HOMA-beta 0 to 12 months Change from Baseline(V2) in insulin secretion by HOMA-beta at 12 months(V6)
OGTT (Fasting and PP2hr) 0 to 12 months Change from baseline in OGTT (Fasting and PP2hr) at 12 months(V6)
Creatinine clearance (MDRD eGFR) at 6 month(V4) at 6 month(V4) Creatinine clearance (MDRD eGFR) at 6 month(V4)
12 month graft survival at 12 months(V6) After date of randomization, evaluate graft survival rate at 12 months(V6)
Proportion of patients with significant proteinuria greater than 1g/gCr at 6 month(V4) at 6 month(V4) Proportion of patients with significant proteinuria greater than 1g/gCr at 6 month(V4)
Proportion of patients with significant proteinuria greater than 1g/gCr at 12 month(V6) at 12 month(V6) Proportion of patients with significant proteinuria greater than 1g/gCr at 12 month(V6)
Number of hospitalization of any cause (except admission for protocol biopsy) at 9 month(V5) at 9 month(V5) Number of hospitalization of any cause (except admission for protocol biopsy) at 9 month(V5)
Needs for anti-diabetic medication or insulin at 3 month(V3) at 3 month(V3) Needs for anti-diabetic medication or insulin at 3 month(V3)
Needs for anti-diabetic medication or insulin at 6 month(V4) at 6 month(V4) Needs for anti-diabetic medication or insulin at 6 month(V4)
Proportion of patients with significant proteinuria greater than 1g/gCr at 9 month(V5) at 9 month(V5) Proportion of patients with significant proteinuria greater than 1g/gCr at 9 month(V5)
Number of hospitalization of any cause (except admission for protocol biopsy) at Baseline(V2) at Baseline(V2) Number of hospitalization of any cause (except admission for protocol biopsy) at Baseline(V2)
Number of opportunistic infections (BKVN) at Baseline(V2) at Baseline(V2) Number of opportunistic infections (BKVN) at Baseline(V2)
Prevalence of NODAT at 3 month(V3) at 3 month(V3) Prevalence of NODAT at 3 month(V3)
Needs for anti-diabetic medication or insulin at Baseline(V2) Needs for anti-diabetic medication or insulin at Baseline(V2)
Needs for anti-diabetic medication or insulin at 12 month(V6) at 12 month(V6) Needs for anti-diabetic medication or insulin at 12 month(V6)
Proportion of patients with significant proteinuria greater than 1g/gCr at Baseline(V2) at Baseline(V2) Proportion of patients with significant proteinuria greater than 1g/gCr at Baseline(V2)
Proportion of patients with significant proteinuria greater than 1g/gCr at 3 month(V3) at 3 month(V3) Proportion of patients with significant proteinuria greater than 1g/gCr at 3 month(V3)
Number of hospitalization of any cause (except admission for protocol biopsy) at 3 month(V3) at 3 month(V3) Number of hospitalization of any cause (except admission for protocol biopsy) at 3 month(V3)
Number of hospitalization of any cause (except admission for protocol biopsy) at 6 month(V4) at 6 month(V4) Number of hospitalization of any cause (except admission for protocol biopsy) at 6 month(V4)
Number of opportunistic infections (BKVN) at 12month(V6) at 12 month(V6) Number of opportunistic infections (BKVN) at 12month(V6)
Prevalence of NODAT at 9 month (V5) at 9 month (V5) Prevalence of NODAT at 9 month (V5)
Insulin resistance by HOMA-IR 0 to 12 months Change from Baseline(V2) in Insulin resistance by HOMA-IR at 12months(V6)
Creatinine clearance (MDRD eGFR) at 3 month(V3) at 3 month(V3) Creatinine clearance (MDRD eGFR) at 3 month(V3)
Creatinine clearance (MDRD eGFR) at 12 month(V6) at 12 month(V6) Creatinine clearance (MDRD eGFR) at 12 month(V6)
12 month patient survival rate at 12 months(V6) After date of randomization, evaluate patient survival rate at 12 months(V6)
Change from baseline in Microalbuminuria(MAU) at 12 months at 12 months(V6) Change from baseline in Microalbuminuria(MAU) at 12 months
Number of episode of biopsy proven acute rejection (BPAR) at 12 month(V6) Cumulative incidence rate of Biopsy Proven Acute Rejection(BPAR) at 12months(V6) after date of randomization.
Prevalence of NODAT at Baseline(V2) at Baseline(V2) Prevalence of NODAT at Baseline(V2)
Prevalence of NODAT at 6 month(V4) at 6 month(V4) Prevalence of NODAT at 6 month(V4)
Prevalence of NODAT at 12 month(V6) at 12 month(V6) Prevalence of NODAT at 12 month(V6)
Creatinine clearance (MDRD eGFR) at 9 month(V5) at 9 month(V5) Creatinine clearance (MDRD eGFR) at 9 month(V5)
Trial Locations
- Locations (1)
division of nephrology;Seoul St Mary's Hospital
🇰🇷Seoul, Korea, Republic of