Disorder Related to Renal Transplantation
Conditions
Keywords
T-cell lymphocyte allo-recognition, CNI-free immunosuppressive regimen, Enzyme-linked immunospot (ELISPOT)
Brief summary
The objective is to assess if low pre-transplantation donor specific T-cell reactive patients measured by Enzyme-linked immunosorbent spot (ELISPOT)assay can be safely managed with Calcineurin inhibitor(CNI)-free Sirolimus(SRL)-based immunosuppression.
Detailed description
Non randomized, pilot, prospective, open-label trial.
Interventions
DRUGPRE-TRANSPLANT (PRE=before)
All patients will start with Thymoglobulin 1 mg/kg before transplant followed by 0,5 mg/kg/d during the next 5 days (total accumulated 3,5 mg/kg). Steroids will be administered at 0,25 mg/kg/d until month 3rd, followed by 0,1 mg/kg/d thereafter. Mycophenolate Mofetil: Pre-transplant 2 grams iv. After transplantation 1g/12 hours, starting iv and changing to oral formulation as soon as patient starts with oral intake (targeting mycophenolic acid (MPA) C0h levels 2-5 µg/mL).
Sponsors
Carlos III Health Institute
Josep M Grinyo
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age of donor and recipient between 18 and 65 years. 2. End-stage renal disease and scheduled to receive a primary or secondary renal allograft from a cadaveric, a living-unrelated, or a living-related donor. Patients scheduled for a second transplant must have maintained their primary graft for at least 6 months after transplantation, with the exception of graft failure due to technical reasons. 3. Panel reactive antibody (PRA) ≤ 20%, with negative standard cross-match. 4. Women of childbearing potential must have a negative serum pregnancy test before randomization. 5. Women of childbearing potential must agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months following discontinuation of assigned treatment. 6. Signed and dated informed consent prior to transplantation.
Exclusion criteria
1. Multiple organ transplants 2. Recipients of adult or pediatric en bloc kidney transplants or dual transplantation or non-heart beating donors. 3. Evidence of active systemic or localized major infection. 4. Evidence of infiltrate, cavitation, or consolidation on chest x-ray obtained during the screening/baseline evaluation. 5. Use of any investigational drug or treatment up to 4 weeks prior to transplantation. 6. Treatment with voriconazole, ketoconazole, itraconazole, fluconazole, clotrimazole, astemizole, pimozide, terfenadine, erythromycin, clarithromycin, telithromycin, troleandomycin, rifampin, rifabutin, or St. John's Wort that is not discontinued prior to randomization. 7. Treatment with aminoglycosides, amphotericin B, cisplatin, cisapride, metoclopramide, cimetidine, bromocriptine, danazol, or other drugs associated with renal dysfunction that are not discontinued prior to randomization. 8. Subjects with a screening/baseline total white blood cell count \< 2,000/mm3 or absolute neutrophil count (ANC) \< 500, platelet count \< 100,000/mm3. 9. Fasting triglycerides \> 400 mg/dL (\> 4.6 mmol/L) or fasting total cholesterol \> 300 mg/dL (\> 7.8 mmol/L) despite optimal lipid-lowering therapy. 10. History of malignancy within 2 years of enrollment (except for adequately treated basal cell or squamous cell carcinoma of the skin). 11. Auto-immune diseases inactive immunosuppressive treatment ( 3 months prior to inclusion). 12. Patient with psychiatric disorders that could be non-compliance for the treatment. 13. Non Caucasian patients. 14. Active peptic ulcers that could produce intestinal absorption disorders. 15. Subjects who are known to be human immunodeficiency virus(HIV) or hepatitis B virus (HBV) positive. Patients with hepatitis C virus (HCV) positive should be excluded if polymerase chain reaction (PCR) positive or transaminates values are ≥2 upper normal value (UNV). 16. Diabetic patients. 17. Body mass index higher than 30 Kg/m2.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of biopsy-confirmed acute rejection episodes | 6 months | To describe cumulative biopsy-confirmed acute rejection in both groups by intention to treat analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of steroid-sensitive acute rejections rejection episodes | 12 months | To describe the percentage of steroid-sensitive acute rejections rejection in both groups by intention to treat analysis. |
| Percentage of steroid-sensitive acute rejection episodes | 6 months | To describe the percentage of steroid-sensitive acute rejections rejection in both groups by intention to treat analysis. |
| Percentage of acute rejection episodes requiring treatment with antilymphocyte antibodies. | 6 months | To describe the need for antibody treatment in acute rejection episodes in both groups by intention to treat analysis. |
| Renal function estimated by Modification of Diet in Renal Disease (MDRD) formula. | 12 months | To describe renal function measured by MDRD in both groups by intention to treat and on therapy analysis. |
| Proteinuria measured in g/day | 6 months | To describe proteinuria in g/day in both groups by intention to treat analysis. |
| Histology at month 6 protocol kidney allograft biopsy | 6 months | To describe histology at month 6 in both groups by intention to treat and on therapy analysis. |
| Percentage of patients with negative ELISPOT | 6 months | To describe percentage of patients with negative ELISPOT in both groups by intention to treat and on therapy analysis. |
| Percentage of patients in group A requiring CNI introduction. | 24 months | To describe the percentage of patients in group A requiring CNI introduction. |
| Percentage of patients presenting adverse events requiring study withdrawal | 24 months | To describe adverse events in the whole group (screening failure plus intention to treat) in both treatments groups. |
| Percentage of biopsy-confirmed acute rejection episodes | 12 months | To describe cumulative biopsy-confirmed acute rejection in both groups by intention to treat analysis. |
| Percentage of acute rejection episodes requiring treatment with antilymphocyte antibodies | 12 months | To describe the need for antibody treatment in acute rejection episodes in both groups by intention to treat analysis. |
Countries
Spain
Outcome results
None listed