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
Condition: Renal Interstitial Fibrosis
MeSH terms: Lung Diseases, Interstitial; Fibrosis
Study type: Interventional
Phase: Phase 3

Summary: 
      Recently, early biomarkers of renal interstitial fibrosis have been identified, amongst them
      de novo expression of vimentin by tubular epithelial cells, which is an intermediate
      filament, and the translocation of beta-catenin into their cytoplasm. These markers, when
      present, suggest that the epithelial cell undergoes a phenomenon well known as "epithelial to
      mesenchymal transition" (EMT) and could behaves like a myo-fibroblast. EMT is highly
      instrumental in several models of tissue fibrosis, including in the kidney. Actually, it has
      not only been demonstrated that these markers are detectable in the renal graft at an early
      time point post-transplant (i.e. as soon as three months), but also that the intensity of
      their expression correlates with the progression of interstitial fibrosis of the graft
      between 3 and 12 months
    


Intervention name(s): Certican®; Neoral; Myfortic; Simulect®; Corticosteroids
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Certican® was supplied to the participating centers by Novartis for the whole duration of the study in the form of tablets containing 0.75, 0.5 and 0.25 mg and packaged in blister packs.; Neoral® was also supplied to participating centers for the entire duration of the study in the form of soft capsules of 10 mg, 25 mg, 50 mg and 100 mg, and packaged in blister packs.; Myfortic ® was supplied to the participating centers for the duration of the study in the form of 180 and 360 mg gastro-resistant, film-coated tablets. Myfortic® treatment was provided to patients preoperatively or within 24 hours post-transplantation according to the practices of the center. The starting dose was generally 1,440 mg/day, in 2 daily oral fractions, administered at 12 hour intervals up to randomization. Depending on the practices of the center and for the first 6 weeks post-transplantation, a maximum daily dose of 2160 mg of Myfortic® could be administered. In the Neoral® group, the daily dose of 1440 mg was maintained throughout the study.
In the Certican® group, the dose was halved (i.e. 720 mg/day) on introducing Certican® and maintained at 720 mg/day until the end of the study.
An increase in the daily dose of Myfortic® (in the Certican® group) was not authorized unless this was a temporary increase that did not exceed a period of 14 consecutive days.; The administration of Simulect® was part of the standard immunosuppressant therapy. This induction therapy was provided to patients in the form of commercial ampoules each containing 20 mg. Simulect® was administered to each patient at the dose of 20 mg on D0 and D4 post-transplantation.; An intravenous steroid treatment could be administered peri or intraoperatively according to local practice at each center. Oral steroid treatment was quickly introduced (in the week following transplantation) at a daily dose of 20 mg and was then reduced and continued throughout the study at a minimum dose of 5 mg/day.
Other intervention name(s): Everolimus; RAD001; Cyclosporine; basiliximab
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Everolimus; Cyclosporins; Basiliximab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: De Novo renal transplantation