Efficacy of Certican® in Combination With Myfortic® in Renal

Summary

The primary objective is to demonstrate the superiority of everolimus plus Myfortic® plus corticosteroids following CNI withdrawal at week 16 compared to tacrolimus plus Myfortic® plus corticosteroids as measured by the change in calculated Glomerular Filtration Rate (cGFR) from baseline to month 12. The key secondary objective is to demonstrate non-inferiority of biopsy-proved acute rejection (BPAR), graft loss, death or loss to follow-up (composite endpoint) at month 12 in patients switched to everolimus plus Myfortic® plus corticosteroids following CNI withdrawal at Week 16 compared to patients maintained on tacrolimus plus Myfortic® plus corticosteroids. Patients will be submitted to monthly GFR determination but, for group comparison, only the GFR measured at month 12 and month 24 of renal transplantation will be used.

Timeline

Start

2011-08

Primary completion

2012-06

Completion

2013-06

Publications

• Background Pilmore HL, Dittmer ID. Calcineurin inhibitor nephrotoxicity: reduction in dose results in marked improvement in renal function in patients with coexisting chronic allograft nephropathy. Clin Transplant. 2002 Jun;16(3):191-5. doi: 10.1034/j.1399-0012.2002.01119.x.
• Background Mendez R, Gonwa T, Yang HC, Weinstein S, Jensik S, Steinberg S; Prograf Study Group. A prospective, randomized trial of tacrolimus in combination with sirolimus or mycophenolate mofetil in kidney transplantation: results at 1 year. Transplantation. 2005 Aug 15;80(3):303-9. doi: 10.1097/01.tp.0000167757.63922.42.
• Background Nankivell BJ, Borrows RJ, Fung CL, O'Connell PJ, Allen RD, Chapman JR. The natural history of chronic allograft nephropathy. N Engl J Med. 2003 Dec 11;349(24):2326-33. doi: 10.1056/NEJMoa020009.
• Background Lorber MI, Mulgaonkar S, Butt KM, Elkhammas E, Mendez R, Rajagopalan PR, Kahan B, Sollinger H, Li Y, Cretin N, Tedesco H; B251 Study Group. Everolimus versus mycophenolate mofetil in the prevention of rejection in de novo renal transplant recipients: a 3-year randomized, multicenter, phase III study. Transplantation. 2005 Jul 27;80(2):244-52. doi: 10.1097/01.tp.0000164352.65613.24.
• Background Johnson RW. The clinical impact of nephrotoxicity in renal transplantation. Transplantation. 2000 Jun 27;69(12 Suppl):SS14-7. doi: 10.1097/00007890-200006271-00004. No abstract available.
• Background Gallon L, Perico N, Dimitrov BD, Winoto J, Remuzzi G, Leventhal J, Gaspari F, Kaufman D. Long-term renal allograft function on a tacrolimus-based, pred-free maintenance immunosuppression comparing sirolimus vs. MMF. Am J Transplant. 2006 Jul;6(7):1617-23. doi: 10.1111/j.1600-6143.2006.01340.x.
• Background Tedesco-Silva H Jr, Vitko S, Pascual J, Eris J, Magee JC, Whelchel J, Civati G, Campbell S, Alves-Filho G, Bourbigot B, Garcia VD, Leone J, Esmeraldo R, Rigotti P, Cambi V, Haas T; 2306 and 2307 study groups. 12-month safety and efficacy of everolimus with reduced exposure cyclosporine in de novo renal transplant recipients. Transpl Int. 2007 Jan;20(1):27-36. doi: 10.1111/j.1432-2277.2006.00414.x.
• Background Ciancio G, Burke GW, Gaynor JJ, Mattiazzi A, Roth D, Kupin W, Nicolas M, Ruiz P, Rosen A, Miller J. A randomized long-term trial of tacrolimus and sirolimus versus tacrolimus and mycophenolate mofetil versus cyclosporine (NEORAL) and sirolimus in renal transplantation. I. Drug interactions and rejection at one year. Transplantation. 2004 Jan 27;77(2):244-51. doi: 10.1097/01.TP.0000101290.20629.DC.
• Background Ciancio G, Burke GW, Gaynor JJ, Ruiz P, Roth D, Kupin W, Rosen A, Miller J. A randomized long-term trial of tacrolimus/sirolimus versus tacrolimums/mycophenolate versus cyclosporine/sirolimus in renal transplantation: three-year analysis. Transplantation. 2006 Mar 27;81(6):845-52. doi: 10.1097/01.tp.0000203894.53714.27.
• Background Ciancio G, Burke GW, Gaynor JJ, Mattiazzi A, Roth D, Kupin W, Nicolas M, Ruiz P, Rosen A, Miller J. A randomized long-term trial of tacrolimus/sirolimus versus tacrolimus/mycophenolate mofetil versus cyclosporine (NEORAL)/sirolimus in renal transplantation. II. Survival, function, and protocol compliance at 1 year. Transplantation. 2004 Jan 27;77(2):252-8. doi: 10.1097/01.TP.0000101495.22734.07.

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