Clinical trial NCT01079143
Conditions: Renal Interstitial Fibrosis
Keywords: De Novo renal transplantation
Sponsor: Novartis Pharmaceuticals
Start date: 2009-09-01; Completion date: 2012-06-01
Enrollment: 194 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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

Detailed description:

Arms: arm 1: Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®. arm 2: Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®. arm 3: Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®. arm 4: Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
Interventions: intervention 1: Certican® intervention 2: Neoral intervention 3: Myfortic intervention 4: Simulect® intervention 5: Corticosteroids
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: 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. intervention 4: 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. intervention 5: 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.

Protocol documents: