TRANSFORM: A novel study design to evaluate the effect of everolimus on long-term outcomes after kidney transplantation

Open Access Journal of Clinical Trials

Volumn 6, Issue , 2013, Pages 45-53

  Pascual, Julio ^a   Srinivas, Titte R ^b   Chadban, Steven ^c   Citterio, Franco ^d   Oppenheimer, Federico ^e   Tedesco, Helio ^f   Henry, Mitchell L ^g   Legendre, Christophe ^h   Watarai, Yoshihiko ⁱ   Sommerer, Claudia ^j   Lee, Po Chang ^k   Hexham, J Mark ^l   Dong, Gaohong ^l   Bernhardt, Peter ^l   Vincenti, Flavio ^m  

^a HOSPITAL DEL MAR   (Spain)

^b MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^c ROYAL PRINCE ALFRED HOSPITAL   (Australia)

^d FONDAZIONE POLICLINICO UNIVERSITARIO A GEMELLI IRCCS   (Italy)

^e HOSPITAL CLÍNIC   (Spain)

^f FEDERAL UNIVERSITY OF SÃO PAULO   (Brazil)

^g THE OHIO STATE UNIVERSITY WEXNER MEDICAL CENTER   (United States)

^h UNIVERSITÉ PARIS DESCARTES   (France)

ⁱ NAGOYA DAINI RED CROSS HOSPITAL   (Japan)

^j UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^k NATIONAL CHENG KUNG UNIVERSITY   (Taiwan)

^l NOVARTIS PHARMA AG   (Switzerland)

^m UNIVERSITY OF CALIFORNIA   (United States)

more..

Author keywords

Calcineurin inhibitor; mTOR inhibitor; Reduced exposure

Indexed keywords

BASILIXIMAB; CALCINEURIN INHIBITOR; CYCLOSPORIN; EVEROLIMUS; MYCOPHENOLIC ACID; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; TACROLIMUS; THYMOCYTE ANTIBODY; COTRIMOXAZOLE; CREATININE; MYCOPHENOLATE MOFETIL; STEROID;

ACUTE GRAFT REJECTION; ACUTE KIDNEY FAILURE; ADULT; ARTICLE; CLINICAL PRACTICE; DELAYED GRAFT FUNCTION; DRUG EFFICACY; EVALUATION AND FOLLOW UP; FEMALE; GLOMERULUS FILTRATION RATE; GRAFT REJECTION; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; KIDNEY ALLOGRAFT; KIDNEY TRANSPLANTATION; MAJOR CLINICAL STUDY; MALE; MORTALITY; MULTICENTER STUDY; NEPHROTOXICITY; OUTCOME ASSESSMENT; RANDOMIZED CONTROLLED TRIAL; RISK FACTOR; CHRONIC KIDNEY DISEASE; CONTROLLED STUDY; FOLLOW UP; GLOMERULUS FILTRATION; GRAFT FAILURE; GRAFT SURVIVAL; IMMUNE DEFICIENCY; OBSERVATIONAL STUDY; PNEUMONIA; PROSPECTIVE STUDY; PROTEINURIA; STUDY DESIGN;

EID: 84902373713     PISSN: None     EISSN: 11791519     Source Type: Journal    
DOI: 10.2147/OAJCT.S63058     Document Type: Article

References (63)

1. US Department of Health and Human Services. Organ Procurement and Transplant Network Annual Data Report 2011. Available from: http://optn.transplant.hrsa.gov/news/newsDetail.asp?id=1589. Accessed April 17, 2014.
2. Gondos A, Döhler B, Brenner H, Opelz G. Kidney graft survival in Europe and the United States: strikingly different long-term outcomes. Transplantation. 2013;95(2):267-274.
3. US Renal Data System. 2012 Atlas of CKD and ESRD. 2012 Annual Data Report. Available from: http://www.usrds.org/atlas12.aspx. Accessed November 18, 2013.
4. Morales JM, Marcén R, del Castillo D, etal. Risk factors for graft loss and mortality after renal transplantation according to recipient age: a prospective multicentre study. Nephrol Dial Transplant. 2012;27 Suppl 4:iv39-iv46.
5. Dunn TB, Noreen H, Gillingham K, etal. Revisiting traditional risk factors for rejection and graft loss after kidney transplantation. Am J Transplant. 2011;11(10):2132-2143.
6. Øien CM, Reisaeter AV, Leivestad T, Dekker FW, Line PD, Os I. Living donor kidney transplantation: the effects of donor age and gender on short-and long-term outcomes. Transplantation. 2007;83(5):600-606.
7. Quiroga I, McShane P, Koo DD, etal. Major effects of delayed graft function and cold ischaemia time on renal allograft survival. Nephrol Dial Transpl. 2006;21(6):1689-1696.
8. Cole EH, Johnston O, Rose CL, Gill JS. Impact of acute rejection and new-onset diabetes on long-term transplant graft and patient survival. Clin J Am Soc Nephrol. 2008;3(3):814-821.
9. McDonald S, Russ G, Campbell S, Chadban S. Kidney transplant rejection in Australia and New Zealand: relationships between rejection and graft outcome. Am J Transplant. 2007;7(5):1201-1208.
10. Pascual J, Marcén R, Zamora J, etal. Very early serum creatinine as a surrogate marker for graft survival beyond 10 years. J Nephrol. 2009;22(1):90-98.
11. Gore JL, Pham PT, Danovitch GM, etal. Obesity and outcome following renal transplantation. Am J Transplant. 2006;6(2):357-363.
12. Pascual J, Zamora J, Pirsch JD. A systematic review of kidney transplantation from expanded criteria donors. Am J Kidney Dis. 2008;52(3):553-586.
13. National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143-3421.
14. Park WD, Larson TS, Griffin MD, Stegall MD. Identification and characterization of kidney transplants with good glomerular filtration rate at 1 year but subsequent progressive loss of renal function. Transplantation. 2012;94(9):931-939.
15. Kasiske BL, Israni AK, Snyder JJ, Skeans MA; Patient Outcomes in Renal Transplantation (PORT) Investigators. The relationship between kidney function and long-term graft survival after kidney transplant. Am J Kidney Dis. 2011;57(3):466-475.
16. Lenihan CR, O'Kelly P, Mohan P, etal. MDRD-estimated GFR at one year post-renal transplant is a predictor of long-term graft function. Ren Fail. 2008;30(4):345-352.
17. Wu J, Li H, Huang H, etal. Slope of changes in renal function in the first year post-transplantation and one-yr estimated glomerular filtration rate together predict long-term renal allograft survival. Clin Transplant. 2010;24(6):862-868.
18. Smith-Palmer J, Kalsekar A, Valentine W. Influence of renal function on long-term graft survival and patient survival in renal transplant recipients. Curr Med Res Opin. 2014;30(2):235-242.
19. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med. 1999;130(6):461-470.
20. Remport A, Molnar MZ, Ambrus C, etal. Impaired renal function is associated with mortality in kidney-transplanted patients. Int Urol Nephrol. 2010;42(3):799-809.
21. Schnitzler MA, Johnston K, Axelrod D, Gheorghian A, Lentine KL. Associations of renal function at 1-year after kidney transplantation with subsequent return to dialysis, mortality, and healthcare costs. Transplantation. 2011;91(12):1347-1356.
22. He X, Moore J, Shabir S, etal. Comparison of the predictive performance of eGFR formulae for mortality and graft failure in renal transplant recipients. Transplantation. 2009;87(3):384-392.
23. US Food and Drug Administration. Endpoints in Clinical Trials of Kidney Transplantation: Public Workshop. Available from: http://www.fda.gov/Drugs/NewsEvents/ucm305308.htm. Accessed November 20, 2013.
24. Committee for Medicinal Products for Human Use. European Medicines Agency. Guideline on clinical investigation of immunosuppressants for solid organ transplantation. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003593.pdf. Accessed November 20, 2013.
25. Campistol JM, de Fijter JW, Nashan B, Holdaas H, Vítko S, Legendre C. Everolimus and long-term outcomes in renal transplantation. Transplantation. 2011;92(Suppl 3):S3-S26.
26. Holdaas H, Midtvedt K, Åsberg A. A drug safety evaluation of everolimus in kidney transplantation. Expert Opin Drug Saf. 2012;11(6): 1013-1022.
27. Chapman JR. Chronic calcineurin inhibitor nephrotoxicity-lest we forget. Am J Transplant. 2011;11(4):693-697.
28. Ojo A, Held PHJ, Port FK, etal. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med. 2003;349(10):931-940.
29. Vitko S, Tedesco H, Eris J, etal. Everolimus with optimized cyclosporine dosing in renal transplant recipients: 6-month safety and efficacy results of two randomized studies. Am J Transplant. 2004;4(4):626-635.
30. Chan L, Greenstein S, Hardy MA, etal; CRADUS09 Study Group. Multicenter, randomized study of the use of everolimus with tacrolimus after renal transplantation demonstrates its effectiveness. Transplantation. 2008;85(6):821-826.
31. Tedesco Silva H Jr, Cibrik D, Johnston T, etal. Everolimus plus reduced-exposure CsA versus mycophenolic acid plus standard-exposure CsA in renal-transplant recipients. Am J Transplant. 2010;10(6):1401-1413.
32. Albano L, Berthoux F, Moal MC, etal; RAD A2420 Study Group. Incidence of delayed graft function and wound healing complications after deceased-donor kidney transplantation is not affected by de novo everolimus. Transplantation. 2009;88(1):69-76.
33. Langer RM, Hené R, Vitko S, etal. Everolimus plus early tacrolimus minimization: a phase III, randomized, open-label, multicentre trial in renal transplantation. Transpl Int. 2012;25(5):592-602.
34. Cibrik D, Silva HT, Vathsala A, etal. Randomized trial of everolimus-facilitated calcineurin-inhibitor minimization over 24 months in renal transplantation. Transplantation. 2013;95(7):933-942.
35. Zeier M, van der Giet M. Calcineurin inhibitor sparing regimens using m-target of rapamycin inhibitors: an opportunity to improve cardiovascular risk following kidney transplantation. Transpl Int. 2011;24(1): 30-42.
36. Gao XM, Wong G, Wang B, etal. Inhibition of mTOR reduces chronic pressure-overload cardiac hypertrophy and fibrosis. J Hypertens. 2006;24(8):1663-1670.
37. Buss SJ, Muenz S, Riffel JH, etal. Beneficial effects of mammalian target of rapamycin inhibition on left ventricular remodeling after myocardial infarction. J Am Coll Cardiol. 2009;54(35):2435-2446.
38. Paoletti E, Amidone M, Cassottana P, Gherzi M, Marsano L, Cannella G. Effect of sirolimus on left ventricular hypertrophy in kidney transplant recipients: a 1-year nonrandomized controlled trial. Am J Kidney Dis. 2008;52(2):324-330.
39. Murbraech K, Holdaas H, Massey R, Undset LH, Aakhus S. Cardiac response to early conversion from calcineurin inhibitor to everolimus in renal transplant recipients: an echocardiographic substudy of the randomized controlled CENTRAL trial. Transplantation. 2014;97(3): 184-188.
40. Mueller MA, Beutner F, Teupser D, Ceglarek U, Thiery J. Prevention of atherosclerosis by the mTOR inhibitor everolimus in LDLR-/-mice despite severe hypercholesterolemia. Atherosclerosis. 2008;98(1): 39-48.
41. Eisen HJ, Kobashigawa J, Starling RC, etal. Everolimus versus mycophenolate mofetil in heart transplantation: a randomized, multicenter trial. Am J Transplant. 2013;13(15):1203-1216.
42. Eisen HJ, Tuzcu EM, Dorent R, etal; RAD B253 Study Group. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N Engl J Med. 2003;349(9):847-858.
43. Seckinger J, Sommerer C, Hinkel UP, Hoffmann O, Zeier M, Schwenger V. Switch of immunosuppression from cyclosporine A to everolimus: impact on pulse wave velocity in stable de-novo renal allograft recipients. J Hypertens. 2008;26(11):2213-2219.
44. Joannidès R, Monteil C, de Ligny BH, etal. Immunosuppressant regimen based on sirolimus decreases aortic stiffness in renal transplant recipients in comparison to cyclosporine. Am J Transplant. 2011;11(11): 2414-2422.
45. Claes KJ, Heye S, Bammens B, etal. Aortic calcifications and arterial stiffness as predictors or cardiovascular events in incident renal transplant patients. Transpl Int. 2013;26(10):973-981.
46. Opelz G, Döhler B. Association of HLA mismatch with death with a functioning graft after kidney transplantation: a collaborative transplant study report. Am J Transplant. 2012;12(11):3031-3038.
47. Opelz G, Döhler B. Association between steroid dosage and death with a functioning graft after kidney transplantation. Am J Transplant. 2013;13(8):2096-2105.
48. Gutiérrez-Dalmau A, Campistol JM. The role of proliferation signal inhibitors in post-transplant malignancies. Nephrol Dial Transplant. 2007;22 Suppl 1:i11-i16.
49. Motzer RJ, Escudier B, Oudard S, etal; RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomized, placebo-controlled phase III trial. Lancet. 2008;372(9637): 449-456.
50. Campbell SB, Walker R, Tai SS, Jiang Q, Russ GR. Randomized controlled trial of sirolimus for renal transplant recipients at high risk for nonmelanoma skin cancer. Am J Transplant. 2012;12(5):1146-1156.
51. Euvrard S, Boissonnat P, Roussoulières A, etal. Effect of everolimus on skin cancers in calcineurin inhibitor-treated heart transplant recipients. Transpl Int. 2010;23(8):855-857.
52. Tapiawala SN, Tinckam KJ, Cardella CJ, etal. Delayed graft function and the risk of death with a functioning graft. J Am Soc Nephrol. 2010;21(1): 153-161.
53. Egli A, Binggeli S, Bodaghi S, etal. Cytomegalovirus and polyomavirus BK posttransplant. Nephrol Dial Transplant. 2007;22 Suppl 8: viii72-viii82.
54. Brennan DC, Legendre C, Patel D, etal. Cytomegalovirus incidence between everolimus versus mycophenolate in de novo renal transplants: pooled analysis of three clinical trials. Am J Transplant. 2011;11(11): 2453-2462.
55. Suwelack B, Malyar V, Koch M, Sester M, Sommerer C. The influence of immunosuppressive agents on BK virus risk following kidney transplantation, and implications for choice of regimen. Transplant Rev (Orlando). 2012;26(3):201-211.
56. Gurk-Turner C, Manitpisitkul W, Cooper M. A comprehensive review of everolimus clinical reports: a new mammalian target of rapamycin inhibitor. Transplantation. 2012;94(7):659-668.
57. Junge G, Bernhardt P, Escrig C, Tedesco Silva H. Surrogate renal endpoints for predicting long-term allograft survival in kidney transplantation. Abstract SA-PO1008 presented at American Society of Nephrology Kidney Week, Atlanta, GA, USA, November 5-10, 2013.
58. Srinivas TR, Flechner SM, Poggio ED, etal. Glomerular filtration rate slopes have significantly improved among renal transplants in the United States. Transplantation. 2010;90(12):1499-1505.
59. Tanaka T, Kyo M, Kokado Y, etal. Correlation between the Banff 97 classification of renal allograft biopsies and clinical outcome. Transpl Int. 2004;17(2):59-64.
60. Banas B, Albano L, Cassuto E, etal; On behalf of the OSAKA Study Group. The impact of acute rejection on renal function-perspectives from the OSAKA study. Transplantation. 2012;94(10S):983.
61. Haas M, Kraus ES, Samaniego-Picota M, Racusen LC, Ni W, Eustace JA. Acute renal allograft rejection with intimal arteritis: Histologic predictors of response to therapy and graft survival. Kidney Int. 2002;61(4):1516-1526.
62. Sis B, Mengel M, Haas M, etal. Banff '09 meeting report: antibody mediated graft deterioration and implementation of Banff working groups. Am J Transplant. 2010;10(3):464-471.
63. Kovarik JM, Curtis JJ, Hricik DE, Pescovitz MD, Scantlebury V, Vasquez A. Differential pharmacokinetic interaction of tacrolimus and cyclosporine on everolimus. Transplant Proc. 2006;38(10): 3456-3458.