PATIENTS THAT RECEIVE A FIRST RENAL ALLOGRAFT TRANSPLANTATION. It has been shown that the assessment of the donor specific T-cell alloimmune response can be successfully performed by using new tools, such as the Elispot assay. The aim of this protocol is to make use of the pre-transplant donor specific cellular alloreactivity assessment by the Elispot assay, in order to evaluate if low aloresponders patients can be safely managed with a CNI-free immunosuppression regimen MedDRA version: 9.1 Le
Conditions
Interventions
Pharmaceutical Form:
INN or Proposed INN: SIROLIMUS
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-
INN or Proposed INN: SIROLIMUS
Concentration u
Sponsors
SERVICIO NEFROLOGIA HOSPITAL BELLVITGE
Eligibility
Sex/Gender
All
Inclusion criteria
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.PRA = 20% 4.Negative cytotoxic T-cell cross-match. 5.Women of childbearing potential must have a negative serum pregnancy test before randomization. 6.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. 7.Signed and dated informed consent prior to transplantation. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 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-inmune diseases in active inmunosupressive treatment ( 3 months prior to inclusion). 12.Patients with psiquiatric disorders that could be non-compliance for the treatment. 13. Active peptic ulcers that could produce intestinal absortion disorders. 14. Subjects who are known to be HIV or HBV positive ( surface antigen, HBV DNA, or e antigen positive). Patients with HCV positive should be excluded if PCR positive or transaminates values are =2UNV. 15. Diabetic patients. 16. Body mass index (BMI) higher than 30 Kg/m2. (See Attachment 5: Nomogram for Determining Body Mass Index). 17. Recipients of kidneys from deceased donor after a cardiac arrest.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To describe cumulative biopsy-confirmed acute rejection at month 6th and month 12th in both groups by intention to treat analysis.;Secondary Objective: 1.To describe the percentage of steroid-sensitive and resistent acute rejections episodes at month 6 and 12 in both groups by intention to treat analysis. 2.To describe renal function measured by MDRD at month 12 and 24 in both groups. 4.To describe proteinuria in g/day at month 6and 12 in both groups. 5.To describe histology at month 6 in both groups . 6.To describe percentage of patients with negative ELISPOT at 6 and 12 months in both groups- 7.To describe the percentage of patients in group A requiring CNI introduction. 8.To describe adverse events in the whole group. 9. To assess if low pre-transplantation donor specific T-cell reactive patients measured by ELISPOT can be safely managed with CNI-free SRL-based immunossuppression. 10.To assess if post-transplant donor specific T-cell alloresponse monitoring together with graft histology assessment could be useful for minimization or strengthen the immunosuppressive therapy in month 6.;Primary end point(s): To describe cumulative biopsy-confirmed acute rejection at month 6th after transplantation and month 12th in both groups by intention to treat analysis. | — |
Countries
Spain
Outcome results
None listed