Selection of Immunosuppression in Kidney Transplant Recipients Depending on Pre-transplant Donor-specific T-cell Reactivity. (SIRES)

Josep M Grinyo

Status and phase: Completed; Phase 4

Conditions: Disorder Related to Renal Transplantation

Treatments: Drug: PRE-TRANSPLANT (PRE=before)

Study type: Interventional

Funder types: Other

Identifiers

NCT01195194

2007-002378-68 (EudraCT Number)

SIRES

Details and patient eligibility

About

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.

Full description

Non randomized, pilot, prospective, open-label trial.

Enrollment: 61 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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61 participants in 2 patient groups

A- negative pre-transplant ELISPOT

Experimental group

Description:

Sirolimus: Start at 5 mg/day as soon as treatment allocation arrives to obtain targeting levels to 8 -15 ng/ml (immunoassay) in the first 3 months, followed by trough levels of 5-10 ng/ml.

Treatment:

Drug: PRE-TRANSPLANT (PRE=before)

B- Positive pre-transplant ELISPOT

Experimental group

Description:

Tacrolimus 0.1 mg/kg/12h starting as soon as treatment allocation arrives to obtain targeting troughs levels of 8-15 ng/ml the first 3 months, followed by trough levels of 5-10 ng/ml until the end of the study.

Treatment:

Drug: PRE-TRANSPLANT (PRE=before)