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

Seoul St. Mary's Hospital

Status and phase: Unknown; Phase 4

Conditions: Kidney; Complications, Allograft

Treatments: Drug: Tacrolimus; Drug: Mycophenolic acid; Drug: Everolimus

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02036554

CRAD001AKR11T

Details and patient eligibility

About

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

Full 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

Enrollment: 234 estimated patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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234 participants in 2 patient groups

Tacrolimus plus Everolimus

Experimental group

Description:

Low dose Tacrolimus + Everolimus

Treatment:

Drug: Everolimus

Drug: Tacrolimus

Tacrolimus plus Mycophenolic acid

Active Comparator group

Description:

standard dose Tacrolimus + Mycophenolic acid

Treatment:

Drug: Mycophenolic acid

Drug: Tacrolimus