Clinical trial NCT02036554: Evaluate Efficacy Study of Combination Therapy of Everolimus and Low Dose Tacrolimus in Renal Allograft Recipients
Official title: To Evaluate Prevention Effect 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Kidney; Complications, Allograft
Lead sponsor: Seoul St. Mary's Hospital
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2014-01-15
Enrollment: 234
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

Eligibility criteria: 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

Primary outcomes:
measure: Change from Baseline in Development of NODAT (Fasting glucose ≥ 126 mg/dL, Random glucose ≥ 200 mg/dL) at 12 months
timeFrame: 0 to 12 month
Secondary outcomes:
measure: Insulin resistance by HOMA-IR
timeFrame: 0 to 12 months
measure: Insulin secretion by HOMA-beta
timeFrame: 0 to 12 months
measure: OGTT (Fasting and PP2hr)
timeFrame: 0 to 12 months
measure: Needs for anti-diabetic medication or insulin
timeFrame: at Baseline(V2)
measure: Needs for anti-diabetic medication or insulin at 3 month(V3)
timeFrame: at 3 month(V3)
measure: Needs for anti-diabetic medication or insulin at 6 month(V4)
timeFrame: at 6 month(V4)
measure: Needs for anti-diabetic medication or insulin at 9 month(V5)
timeFrame: at 9 month(V5)
measure: Needs for anti-diabetic medication or insulin at 12 month(V6)
timeFrame: at 12 month(V6)
measure: Creatinine clearance (MDRD eGFR) at Baseline(V2)
timeFrame: at Baseline(V2)
measure: Creatinine clearance (MDRD eGFR) at 3 month(V3)
timeFrame: at 3 month(V3)
measure: Creatinine clearance (MDRD eGFR) at 6 month(V4)
timeFrame: at 6 month(V4)
measure: Creatinine clearance (MDRD eGFR) at 9 month(V5)
timeFrame: at 9 month(V5)
measure: Creatinine clearance (MDRD eGFR) at 12 month(V6)
timeFrame: at 12 month(V6)
measure: 12 month graft survival
timeFrame: at 12 months(V6)
measure: 12 month patient survival rate
timeFrame: at 12 months(V6)
measure: Change from baseline in Microalbuminuria(MAU) at 12 months
timeFrame: at 12 months(V6)
measure: Proportion of patients with significant proteinuria greater than 1g/gCr at Baseline(V2)
timeFrame: at Baseline(V2)
measure: Proportion of patients with significant proteinuria greater than 1g/gCr at 3 month(V3)
timeFrame: at 3 month(V3)
measure: Proportion of patients with significant proteinuria greater than 1g/gCr at 6 month(V4)
timeFrame: at 6 month(V4)
measure: Proportion of patients with significant proteinuria greater than 1g/gCr at 9 month(V5)
timeFrame: at 9 month(V5)
measure: Proportion of patients with significant proteinuria greater than 1g/gCr at 12 month(V6)
timeFrame: at 12 month(V6)
measure: Number of episode of biopsy proven acute rejection (BPAR)
timeFrame: at 12 month(V6)
measure: Number of hospitalization of any cause (except admission for protocol biopsy) at Baseline(V2)
timeFrame: at Baseline(V2)
measure: Number of hospitalization of any cause (except admission for protocol biopsy) at 3 month(V3)
timeFrame: at 3 month(V3)
measure: Number of hospitalization of any cause (except admission for protocol biopsy) at 6 month(V4)
timeFrame: at 6 month(V4)
measure: Number of hospitalization of any cause (except admission for protocol biopsy) at 9 month(V5)
timeFrame: at 9 month(V5)
measure: Number of hospitalization of any cause (except admission for protocol biopsy) at 12 month(V6)
timeFrame: at 12 month(V6)
measure: Number of opportunistic infections (BKVN) at Baseline(V2)
timeFrame: at Baseline(V2)
measure: Number of opportunistic infections (BKVN) at 12month(V6)
timeFrame: at 12 month(V6)
measure: Prevalence of NODAT at Baseline(V2)
timeFrame: at Baseline(V2)
measure: Prevalence of NODAT at 3 month(V3)
timeFrame: at 3 month(V3)
measure: Prevalence of NODAT at 6 month(V4)
timeFrame: at 6 month(V4)
measure: Prevalence of NODAT at 9 month (V5)
timeFrame: at 9 month (V5)
measure: Prevalence of NODAT at 12 month(V6)
timeFrame: at 12 month(V6)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: division of nephrology;Seoul St Mary's Hospital
Study officials:
affiliation: St Mary's Hospital, London
name: Chul-Woo Yang, MD
role: PRINCIPAL_INVESTIGATOR
References: