NCT01079143 - Progression of Renal Interstitial Fibrosis / Tubular Atrophy (IF/TA) According to Epithelial-mesenchymal Transition (EMT) and Immunosuppressive Regimen (Everolimus Based Versus CNI Based) in de Novo Renal Transplant Recipients | Crick

Eligibility

Sex: ALLMin age: 19 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Recipient of a primary or secondary deceased or living (related or not) donor kidney transplant and who requires basiliximab induction therapy. * Cold ischemia time \< 30 hours. * Women of child-bearing age, even those with a history of infertility, must have had a negative pregnancy test during the 7 days before screening or at the time of screening, and must use a recognized and reliable method of contraception throughout the study and for 2 months after discontinuing the study treatment. * Patients who want and are able to take part in the entire study, and have given their written consent. * Patients who are registered with a French national health insurance scheme or are covered by such a scheme. Exclusion Criteria: * Recipient of multi-organ transplantation, including dual kidneys, or who have previously received non renal transplant organ. * Patients receiving a graft from a non-heart-beating donor. * Anti-HLA antibody levels ≥ 20% in the last 3 months before the inclusion. * ABO incompatible graft or with positive cross match T. * Severe hyperlipidemia: total cholesterol ≥ 9.1 mmol/L (≥ 350 mg/dL) and/or triglycerides ≥ 8.5 mmol/L (≥ 750 mg/dL) despite appropriate lipid-lowering therapy. * Known hypersensitivity or contraindications to mycophenolic acid, cyclosporine or lactose. * Known hypersensitivity or contraindications to macrolides or drugs of the mTOR inhibitor class. * HIV seropositive, or active chronic hepatitis B (HBs Ab) or C. Results obtained during the 6 months before the inclusion are accepted. Recipients from donors with hepatitis B or C will be excluded. * Patients with thrombocytopenia (≤ 75000/mm3), absolute neutrophil count (≤ 1500/mm3), leukocytopenia (≤ 2500/mm3) and/or hemoglobin \< 8g/dL at the inclusion visit. * ASAT, ALAT or total bilirubin ≥ 3 UNL. * Uncontrolled severe infection, severe allergy requiring an acute or chronic treatment. * Patients with a malignant disease or previous malignancy in the past 5 years, with the exception of excised basal cell or squamous cell carcinoma and in situ cervical cancer treated. * Medical or surgical condition, with the exception of the transplantation, which in the investigator's opinion could exclude the patient. * Women who are pregnant, breastfeeding or of reproductive age and refuse or are unable to use a recognized and reliable method of contraception. * Patients with symptoms of significant mental or somatic disease. Inability to cooperate or communicate with the investigator. * Patients under supervision or guardianship or any patient subject to legal protection Randomization criteria: Eligibility criteria (no later than 4 months post-transplantation: * Renal graft biopsy performed at M3 and adequate histological material sent within the deadline for the determination of EMT. * Woman of child-bearing potential, even in case of a history of infertility, must use a recognized and reliable method of contraception throughout the study and for 2 months after discontinuing the study treatment. Non-eligibility criteria (no later than 4 months post-transplantation): * Acute rejection histologically proven between transplantation and randomization (local reading). * Acute subclinical rejection diagnosed on the M3 biopsy (except borderline lesions) (local reading). * Positive anti-donor antibodies at M3. * Estimated glomerular filtration rate (eGFR) \< 30 ml/min/1.73 m2 (MDRDa). * Proteinuria ≥ 1 g/24h. * Severe hyperlipidemia: total cholesterol ≥ 9.1 mmol/L (≥ 350 mg/dL) and/or triglycerides ≥ 8.5 mmol/L (≥ 750 mg/dL) despite appropriate lipid-lowering therapy. * Thrombocytopenia (≤ 75000/mm3), absolute neutrophil count (≤ 1500/mm3), leukocytopenia (≤ 2500/mm3) and/or hemoglobin \< 8 g/dL. * ASAT, ALAT or total bilirubin ≥ 3 UNL. * Medical or surgical condition which in the investigator's opinion might exclude the patient. Other protocol-defined inclusion/exclusion criteria may apply.

Outcomes

Primary Outcomes

Number of Participants With Progression of Renal Graft Fibrosis (Primary Comparison - ITT Population

Progression of Interstitial Fibrosis/Tabular Atrophy (IF/TA) is the percentage (%) of participants with an increase \>= 1 in IF/TA grade according to Banff (2005 - 2007)according to Epithelial-mesenchymal transition (EMT) profile and by treatment groups. Grade I (the better): mild interstitial fibrosis and tubular atrophy (\<25% of cortical area) Grade II : moderate interstitial fibrosis and tubular atrophy (26-50% of cortical area) Grade III (the worse) : severe interstitial fibrosis and tubular atrophy (\>50% of cortical area)

Time frame: Month 3 (M3) and Month 12 (M12) post transplantation

Secondary Outcomes

Interstitial Fibrosis/Tabular Atrophy (IF/TA)

Incidence and severity of IF/TA according to 2005/2007 Banff classification system grades (grades l to lll). IF/TA grade was assessed during centralized reading according to the Banff 2005/2007 classification comprising grade I (\<25%), grade II (25-50%) and grade III (\>50% of lesions).