PROPHYLAXIS OF REJECTION AFTER KIDNEY TRANSPLANTATION MedDRA version: 20.0 Level: PT Classification code 10023439 Term: Kidney transplant rejection System Organ Class: 10021428 - Immune system disorders
Conditions
Sponsors
ORIOL BESTARD
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Adult men and women (= 18 years). 2) Receptors of a first kidney transplant from a living donor. 3) AB0 compatible transplant. 4) Patients with a calculated PRA 35 mlU / ml). Potentially Fertile Women should have a pregnancy test with a negative result performed within 72 hours prior to the start of the trial. 7) Sexually active (including vasectomized) males who are receiving MMF treatment should accept the use of barrier contraception during MMF treatment and during the 90 days thereafter. Potentially fertile couples of these patients should use a reliable method of contraception during the same period, in order to minimize the risk of pregnancy. 8) Patients should agree not to donate blood during MMF treatment and for 6 weeks thereafter. Males should not donate sperm during MMF treatment and up to 90 days after finishing MMF. 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 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 64
Exclusion criteria
Exclusion criteria: 1) Patients with a calculated PRA > 75% by solid-phase technique and/or presence of current or historical donor specific class I or class II anti-HLA antibodies (DSA). 2) Cross Match positive result. 3) Patients receiving a graft from a deceased donor. 4) Patients who have undergone a previous solid organ transplant (including renal transplantation) or who are going to receive another solid organ transplant concomitantly. 5) Patients with any of the following basic kidney diseases: Primary focal and segmental glomerulosclerosis Atypical Uremic Hemolytic Syndrome (aHUS) / Thrombotic Thrombotic Syndrome Thrombocytopenic. 6) Patients with active Hepatitis B virus (HBV) infection and / or active Hepatitis C virus infection (positive PCR result) at the time of transplantation. 7) Patients with known Human Immunodeficiency Virus (HIV) infection. 8) Patients with active systemic infection requiring continued antibiotic administration. 9) Patients with any neoplasia except localized skin cancer receiving appropriate treatment. 10) Patients with severe anemia (hemoglobin 6g / dl. 12) Patients with intestinal pathology or severe diarrhea that may decrease absorption according to medical criteria. 13) Patients with known hypersensitivity to any of the drugs used in this study. 14) Patients who have received any investigational drug within 30 days prior to their inclusion in this study. 15) Potentially fertile women who do not agree to use reliable contraceptive measures during the trial, who are pregnant, breastfeeding or have a positive pregnancy test at the time of enrollment. 16) Patients who are legally detained in an official institution.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of the trial is to determine the effect of individualizing immunosuppressive therapy based on stratification of baseline immunological risk according to 2 biomarkers (ELISPOT IFN-G d-sp and HLA Eplets Missmatch), in a composed end-point: loss of renal function, incidence of acute rejection and development of dnDSA at 2 years of follow-up in renal transplant patients of living donor compared to patients followed according to standard non-individualized immunosuppressive regimen;Secondary Objective: To assess whether individualized stratification of immunological risk and therapeutic optimization reduces: - patient mortality - loss of renal graft - the development of subclinical and chronic rejection determined in protocol biopsies at 3 and 24 months - Opportunistic infections - the metabolopathies derived from the treatment (diabetes mellitus, dyslipidemia and hypertension) - malignancies (cutaneous and non-cutaneous cancer) at 2 years of follow-up - the economic cost. Evaluate changes: - in the allogenic d-sp response over the 2-year follow-up (dnDSA, ELISPOT IFN- and d-sp, cytokines in urine) - the transcriptional profile of rejection risk according to the kSORT test - the antiviral cellular response to CMV, EBV and VBK viruses.;Primary end point(s): The main variable is a composite variable at 2 years of follow-up, including loss of renal function, incidence of acute clinical rejection, and development of "de novo" (dn) Donor Specific Antibodies (DSA).;Timepoint(s) of evaluation of this end point: 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary variables: A- Mortality from any cause at 24 months B- Loss of renal graft at 24 months C- Incidence and severity of subclinical and chronic rejection (according to protocol biopsies at 3 and 24 months) D- Incidence of opportunistic infections at 24 months E- Incidence of treatment-derived metabolopathies (diabetes mellitus, dyslipidemia and hypertension) at 24 months F- Incidence of cardiovascular events at 24 months G- Incidence of malignancy (cutaneous and non-cutaneous cancer) at 24 months H- Proportion of patients who maintain treatment according to the protocol at the end of the trial. I- Changes in the immune response at 24 months according to biomarkers: - allogeneic response (dn-DSA, ELISPOT IFN-G d-sp, Memory B cell Elispot, urinary cytokines CXCL9 and CXCL10) - transcriptional profile in blood of risk of rejection according to the kSORT test Antiviral cell response to CMV, EBV, VBK; NKG2 J- Economic cost. K- Serious adverse reactions (serious adverse events with possible causal relationship with immunosuppressive treatment).;Timepoint(s) of evaluation of this end point: 24 months | — |
Countries
Netherlands, Spain
Contacts
Public ContactCAROLINA POLO
HOSPITAL UNIVERSITARI DE BELLVITGE-IDIBELL
Outcome results
None listed