Conversion to Everolimus From Calcineurin Inhibitor With Mycophenolic Acid: Impact on Long Term Renal Function in Liver Transplantation.

Summary

This study will examine the renal sparing impact of implementing a strategy of conversion to everolimus from a calcineurin inhibitor based immunosuppressive protocol at 3 months post liver transplant

Timeline

Start

2013-12-16

Primary completion

2019-07-31

Completion

2019-07-31

Publications

• Background Burra P, Senzolo M, Masier A, Prestele H, Jones R, Samuel D, Villamil F. Factors influencing renal function after liver transplantation. Results from the MOST, an international observational study. Dig Liver Dis. 2009 May;41(5):350-6. doi: 10.1016/j.dld.2008.09.018. Epub 2008 Nov 28.
• Background Gonwa TA, Mai ML, Melton LB, Hays SR, Goldstein RM, Levy MF, Klintmalm GB. End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment. Transplantation. 2001 Dec 27;72(12):1934-9. doi: 10.1097/00007890-200112270-00012.
• Background Ojo AO, Held PJ, Port FK, Wolfe RA, Leichtman AB, Young EW, Arndorfer J, Christensen L, Merion RM. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med. 2003 Sep 4;349(10):931-40. doi: 10.1056/NEJMoa021744.
• Background Velidedeoglu E, Bloom RD, Crawford MD, Desai NM, Campos L, Abt PL, Markmann JW, Mange KC, Olthoff KM, Shaked A, Markmann JF. Early kidney dysfunction post liver transplantation predicts late chronic kidney disease. Transplantation. 2004 Feb 27;77(4):553-6. doi: 10.1097/01.tp.0000114609.99558.41.
• Background Wadei HM, Geiger XJ, Cortese C, Mai ML, Kramer DJ, Rosser BG, Keaveny AP, Willingham DL, Ahsan N, Gonwa TA. Kidney allocation to liver transplant candidates with renal failure of undetermined etiology: role of percutaneous renal biopsy. Am J Transplant. 2008 Dec;8(12):2618-26. doi: 10.1111/j.1600-6143.2008.02426.x.
• Background Randhawa PS, Shapiro R. Chronic renal failure after liver transplantation. Am J Transplant. 2005 May;5(5):967-8. doi: 10.1111/j.1600-6143.2005.00819.x. No abstract available.
• Background McCauley J, Van Thiel DH, Starzl TE, Puschett JB. Acute and chronic renal failure in liver transplantation. Nephron. 1990;55(2):121-8. doi: 10.1159/000185938.
• Background Fisher NC, Nightingale PG, Gunson BK, Lipkin GW, Neuberger JM. Chronic renal failure following liver transplantation: a retrospective analysis. Transplantation. 1998 Jul 15;66(1):59-66. doi: 10.1097/00007890-199807150-00010.
• Background Neuberger JM, Mamelok RD, Neuhaus P, Pirenne J, Samuel D, Isoniemi H, Rostaing L, Rimola A, Marshall S, Mayer AD; ReSpECT Study Group. Delayed introduction of reduced-dose tacrolimus, and renal function in liver transplantation: the 'ReSpECT' study. Am J Transplant. 2009 Feb;9(2):327-36. doi: 10.1111/j.1600-6143.2008.02493.x. Epub 2008 Dec 15.
• Background Chapman TM, Perry CM. Everolimus. Drugs. 2004;64(8):861-72; discussion 873-4. doi: 10.2165/00003495-200464080-00005.
• Background Levy G, Schmidli H, Punch J, Tuttle-Newhall E, Mayer D, Neuhaus P, Samuel D, Nashan B, Klempnauer J, Langnas A, Calmus Y, Rogiers X, Abecassis M, Freeman R, Sloof M, Roberts J, Fischer L. Safety, tolerability, and efficacy of everolimus in de novo liver transplant recipients: 12- and 36-month results. Liver Transpl. 2006 Nov;12(11):1640-8. doi: 10.1002/lt.20707.
• Background Nashan B. Early clinical experience with a novel rapamycin derivative. Ther Drug Monit. 2002 Feb;24(1):53-8. doi: 10.1097/00007691-200202000-00010.
• Background Chan L, Greenstein S, Hardy MA, Hartmann E, Bunnapradist S, Cibrik D, Shaw LM, Munir L, Ulbricht B, Cooper M; CRADUS09 Study Group. Multicenter, randomized study of the use of everolimus with tacrolimus after renal transplantation demonstrates its effectiveness. Transplantation. 2008 Mar 27;85(6):821-6. doi: 10.1097/TP.0b013e318166927b.
• Background Everson GT. Everolimus and mTOR inhibitors in liver transplantation: opening the "box". Liver Transpl. 2006 Nov;12(11):1571-3. doi: 10.1002/lt.20845. No abstract available.
• Background De Simone P, Carrai P, Precisi A, Petruccelli S, Baldoni L, Balzano E, Ducci J, Caneschi F, Coletti L, Campani D, Filipponi F. Conversion to everolimus monotherapy in maintenance liver transplantation: feasibility, safety, and impact on renal function. Transpl Int. 2009 Mar;22(3):279-86. doi: 10.1111/j.1432-2277.2008.00768.x. Epub 2008 Dec 2.
• Background Johnson RW, Kreis H, Oberbauer R, Brattstrom C, Claesson K, Eris J. Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure. Transplantation. 2001 Sep 15;72(5):777-86. doi: 10.1097/00007890-200109150-00007.
• Background Oberbauer R, Segoloni G, Campistol JM, Kreis H, Mota A, Lawen J, Russ G, Grinyo JM, Stallone G, Hartmann A, Pinto JR, Chapman J, Burke JT, Brault Y, Neylan JF; Rapamune Maintenance Regimen Study Group. Early cyclosporine withdrawal from a sirolimus-based regimen results in better renal allograft survival and renal function at 48 months after transplantation. Transpl Int. 2005 Jan;18(1):22-8. doi: 10.1111/j.1432-2277.2004.00052.x.
• Background Ekberg H. Calcineurin inhibitor sparing in renal transplantation. Transplantation. 2008 Sep 27;86(6):761-7. doi: 10.1097/TP.0b013e3181856f39.
• Background Baboolal K. A phase III prospective, randomized study to evaluate concentration-controlled sirolimus (rapamune) with cyclosporine dose minimization or elimination at six months in de novo renal allograft recipients. Transplantation. 2003 Apr 27;75(8):1404-8. doi: 10.1097/01.TP.0000063703.32564.3B.
• Background Webster AC, Lee VW, Chapman JR, Craig JC. Target of rapamycin inhibitors (sirolimus and everolimus) for primary immunosuppression of kidney transplant recipients: a systematic review and meta-analysis of randomized trials. Transplantation. 2006 May 15;81(9):1234-48. doi: 10.1097/01.tp.0000219703.39149.85.
• Background Eisen HJ, Tuzcu EM, Dorent R, Kobashigawa J, Mancini D, Valantine-von Kaeppler HA, Starling RC, Sorensen K, Hummel M, Lind JM, Abeywickrama KH, Bernhardt P; RAD B253 Study Group. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N Engl J Med. 2003 Aug 28;349(9):847-58. doi: 10.1056/NEJMoa022171.
• Background Levy GA, Grant D, Paradis K, Campestrini J, Smith T, Kovarik JM. Pharmacokinetics and tolerability of 40-0-[2-hydroxyethyl]rapamycin in de novo liver transplant recipients. Transplantation. 2001 Jan 15;71(1):160-3. doi: 10.1097/00007890-200101150-00028.
• Background Gomez-Camarero J, Salcedo M, Rincon D, Lo Iacono O, Ripoll C, Hernando A, Sanz C, Clemente G, Banares R. Use of everolimus as a rescue immunosuppressive therapy in liver transplant patients with neoplasms. Transplantation. 2007 Sep 27;84(6):786-91. doi: 10.1097/01.tp.0000280549.93403.dd.
• Background Yu SF, Wu LH, Zheng SS. Genetic factors for individual administration of immunosuppressants in organ transplantation. Hepatobiliary Pancreat Dis Int. 2006 Aug;5(3):337-44.
• Background Chaudhary MA, Stearns SC. Estimating confidence intervals for cost-effectiveness ratios: an example from a randomized trial. Stat Med. 1996 Jul 15;15(13):1447-58. doi: 10.1002/(SICI)1097-0258(19960715)15:133.0.CO;2-V.
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• Background Lothgren M, Zethraeus N. Definition, interpretation and calculation of cost-effectiveness acceptability curves. Health Econ. 2000 Oct;9(7):623-30. doi: 10.1002/1099-1050(200010)9:73.0.co;2-v.
• Background Fairbanks KD, Eustace JA, Fine D, Thuluvath PJ. Renal function improves in liver transplant recipients when switched from a calcineurin inhibitor to sirolimus. Liver Transpl. 2003 Oct;9(10):1079-85. doi: 10.1053/jlts.2003.50183.

Drugs

Indications