The Calcineurin Inhibitor-Sparing (CIS) Trial - individualised calcineurin-inhibitor treatment by immunomonitoring in renal allograft recipients: Protocol for a randomised controlled trial

Trials

Volumn 15, Issue 1, 2014, Pages

  Sommerer, Claudia ^a   Schaier, Matthias ^a   Morath, Christian ^a   Schwenger, Vedat ^a   Rauch, Geraldine ^b   Giese, Thomas ^a   Zeier, Martin ^a  

^a UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^b UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

Calcineurin inhibitor; Ciclosporin A; CIS study; Gene expression; Immunomonitoring; Immunosuppression; Minimisation; NFAT; Renal transplantation

Indexed keywords

CREATININE; CYCLOSPORIN A; MYCOPHENOLIC ACID; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; TRANSCRIPTION FACTOR NFAT; CALCINEURIN INHIBITOR; CYCLOSPORIN; IMMUNOSUPPRESSIVE AGENT;

ACUTE GRAFT REJECTION; ADULT; ARTERIAL STIFFNESS; ARTICLE; CARDIOVASCULAR RISK; CONTROLLED STUDY; CREATININE BLOOD LEVEL; FEMALE; GENE EXPRESSION; GLOMERULUS FILTRATION RATE; GRAFT RECIPIENT; HUMAN; HUMAN TISSUE; IMMUNOSUPPRESSIVE TREATMENT; KIDNEY ALLOGRAFT; KIDNEY GRAFT REJECTION; KIDNEY TRANSPLANTATION; MAJOR CLINICAL STUDY; MALE; PROSPECTIVE STUDY; PULSE WAVE; QUANTITATIVE ANALYSIS; RANDOMIZED CONTROLLED TRIAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK ASSESSMENT; ADVERSE EFFECTS; BLOOD; CLINICAL PROTOCOL; COMPARATIVE STUDY; DRUG EFFECTS; DRUG MONITORING; GENE EXPRESSION REGULATION; GENETICS; GERMANY; GRAFT REJECTION; GRAFT SURVIVAL; IMMUNOLOGICAL MONITORING; IMMUNOLOGY; METABOLISM; METHODOLOGY; PREDICTIVE VALUE; PROCEDURES; TIME FACTOR; TREATMENT OUTCOME;

CALCINEURIN INHIBITORS; CLINICAL PROTOCOLS; CYCLOSPORINE; DRUG MONITORING; GENE EXPRESSION REGULATION; GERMANY; GRAFT REJECTION; GRAFT SURVIVAL; HUMANS; IMMUNOSUPPRESSIVE AGENTS; KIDNEY TRANSPLANTATION; MONITORING, IMMUNOLOGIC; NFATC TRANSCRIPTION FACTORS; PREDICTIVE VALUE OF TESTS; PROSPECTIVE STUDIES; PULSE WAVE ANALYSIS; RESEARCH DESIGN; TIME FACTORS; TREATMENT OUTCOME;

EID: 84924680488     PISSN: None     EISSN: 17456215     Source Type: Journal    
DOI: 10.1186/1745-6215-15-489     Document Type: Article

References (41)

1. Meier-Kriesche HU, Li S, Gruessner RW, Fung JJ, Bustami RT, Barr ML, Leichtman AB: Immunosuppression: evolution in practice and trends, 1994-2004. Am J Transplant 2006, 6:1111-1131.10.1111/j.1600-6143.2006.01270.x.
2. Hariharan S, Johnson CP, Bresnahan BA, Taranto SE, McIntosh MJ, Stablein D: Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med 2000, 342:605-612.10.1056/NEJM200003023420901.
3. Ojo AO: Cardiovascular complications after renal transplantation and their prevention. Transplantation 2006, 82:603-611.
4. Maréchal C, Coche E, Goffin E, Dragean A, Schlieper G, Nguyen P, Floege J, Kanaan N, Devuyst O, Jadoul M: Progression of coronary artery calcification and thoracic aorta calcification in kidney transplant recipients. Am J Kidney Dis 2012, 59:258-269.10.1053/j.ajkd.2011.07.019.
5. 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, 349:2326-2333.10.1056/NEJMoa020009.
6. Budde K, Becker T, Arns W, Sommerer C, Reinke P, Eisenberger U, Kramer S, Fischer W, Gschaidmeier H, Pietruck F, ZEUS Study Investigators: Everolimus-based, calcineurin-inhibitor-free regimen in recipients of de-novo kidney transplants: an open-label, randomised, controlled trial. Lancet 2011, 377:837-847.10.1016/S0140-6736(10)62318-5.
7. Rostaing L, Vincenti F, Grinyó J, Rice KM, Bresnahan B, Steinberg S, Gang S, Gaite LE, Moal MC, Mondragón-Ramirez GA, Kothari J, Pupim L, Larsen CP: Long-term belatacept exposure maintains efficacy and safety at 5 years: results from the long-term extension of the BENEFIT study. Am J Transplant 2013, 13:2875-2883.10.1111/ajt.12460.
8. Everly MJ, Rebellato LM, Haisch CE, Ozawa M, Parker K, Briley KP, Catrou PG, Bolin P, Kendrick WT, Kendrick SA, Harland RC, Terasaki PI: Incidence and impact of de novo donor-specific alloantibody in primary renal allografts. Transplantation 2013, 95:410-417.10.1097/TP.0b013e31827d62e3.
9. Ekberg H, Tedesco-Silva H, Demirbas A, Vítko S, Nashan B, Gürkan A, Margreiter R, Hugo C, Grinyó JM, Frei U, Vanrenterghem Y, Daloze P, Halloran PF, ELITE-Symphony Study: Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med 2007, 357:2562-2575.10.1056/NEJMoa067411.
10. Glander P, Sommerer C, Arns W, Ariatabar T, Kramer S, Vogel EM, Shipkova M, Fischer W, Zeier M, Budde K: Pharmacokinetics and pharmacodynamics of intensified versus standard dosing of mycophenolate sodium in renal transplant patients. Clin J Am Soc Nephrol 2010, 5:503-511.10.2215/CJN.06050809.
11. Sommerer C, Glander P, Arns W, Ariatabar T, Kramer S, Vogel EM, Shipkova M, Fischer W, Liefeldt L, Hackenberg R, Schmidt J, Zeier M, Budde K: Safety and efficacy of intensified versus standard dosing regimens of enteric-coated mycophenolate sodium in de novo renal transplant patients. Transplantation 2011, 91:779-785.
12. de Jonge H, Naesens M, Kuypers DR: New insights into the pharmacokinetics and pharmacodynamics of the calcineurin inhibitors and mycophenolic acid: possible consequences for therapeutic drug monitoring in solid organ transplantation. Ther Drug Monit 2009, 31:416-435.10.1097/FTD.0b013e3181aa36cd.
13. Clipstone NA, Crabtree GR: Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation. Nature 1992, 357:695-697.10.1038/357695a0.
14. O'Keefe SJ, Tamura J, Kincaid RL, Tocci MJ, O'Neill EA: FK-506-and CsA-sensitive activation of the interleukin-2 promoter by calcineurin. Nature 1992, 357:692-694.10.1038/357692a0.
15. Kel A, Kel-Margoulis O, Babenko V, Wingender E: Recognition of NFATp/AP-1 composite elements within genes induced upon the activation of immune cells. J Mol Biol 1999, 288:353-376.10.1006/jmbi.1999.2684.
16. Giese T, Zeier M, Schemmer P, Uhl W, Schoels M, Dengler T, Büchler M, Meuer S: Monitoring of NFAT-regulated gene expression in the peripheral blood of allograft recipients: a novel perspective toward individually optimized drug doses of ciclosporin A. Transplantation 2004, 77:339-344.10.1097/01.TP.0000109260.00094.01.
17. Sommerer C, Meuer S, Zeier M, Giese T: Calcineurin inhibitors and NFAT-regulated gene expression. Clin Chim Acta 2012, 413:1379-1386.10.1016/j.cca.2011.09.041.
18. Sommerer C, Konstandin M, Dengler T, Schmidt J, Meuer S, Zeier M, Giese T: Pharmacodynamic monitoring of ciclosporin A in renal allograft recipients shows a quantitative relationship between immunosuppression and the occurrence of recurrent infections and malignancies. Transplantation 2006, 82:1280-1285.10.1097/01.tp.0000243358.75863.57.
19. Sommerer C, Giese T, Schmidt J, Meuer S, Zeier M: Ciclosporin A tapering monitored by NFAT-regulated gene expression: a new concept of individual immunosuppression. Transplantation 2008, 85:15-21.10.1097/01.tp.0000296824.58884.55.
20. Sommerer C, Hartschuh W, Enk A, Meuer S, Zeier M, Giese T: Pharmacodynamic immune monitoring of NFAT-regulated genes predicts skin cancer in elderly long-term renal transplant recipients. Clin Transplant 2008, 22:549-554.10.1111/j.1399-0012.2008.00819.x.
21. Sommerer C, Schnitzler P, Meuer S, Zeier M, Giese T: Pharmacodynamic monitoring of cyclosporin A reveals risk of opportunistic infections and malignancies in renal transplant recipients 65 years and older. Ther Drug Monit 2011, 33:694-698.10.1097/FTD.0b013e318237e33c.
22. Dannewitz B, Kruck EM, Staehle HJ, Eickholz P, Giese T, Meuer S, Kaever V, Zeier M, Sommerer C: Cyclosporine-induced gingival overgrowth correlates with NFAT-regulated gene expression: a pilot study. J Clin Periodontol 2011, 38:984-991.10.1111/j.1600-051X.2011.01773.x.
23. Zahn A, Schott N, Hinz U, Stremmel W, Schmidt J, Ganten T, Gotthardt D, Meuer S, Zeier M, Giese T, Sommerer C: Immunomonitoring of nuclear factor of activated T-cell-regulated gene expression: the first clinical trial in liver allograft recipients. Liver Transpl 2011, 17:466-473.10.1002/lt.22254.
24. Steinebrunner N, Sandig C, Sommerer C, Hinz U, Giese T, Stremmel W, Zahn A: Reduced residual gene expression of nuclear factor of activated T-cell-regulated genes correlates with the risk of cytomegalovirus infection after liver transplantation. Transpl Infect Dis 2014, 16:379-386.10.1111/tid.12206.
25. Steinebrunner N, Sandig C, Sommerer C, Hinz U, Giese T, Stremmel W, Zahn A: Pharmacodynamic monitoring of nuclear factor of activated T-cell-regulated gene expression in liver allograft recipients on immunosuppressive therapy with calcineurin inhibitors in the course of time and correlation with acute rejection episodes-a prospective study. Ann Transplant 2014, 19:32-40.
26. Konstandin MH, Sommerer C, Doesch A, Zeier M, Meuer SC, Katus HA, Dengler TJ, Giese T: Pharmacodynamic cyclosporine A-monitoring: relation of gene expression in lymphocytes to cyclosporine blood levels in cardiac allograft recipients. Transpl Int 2007, 20:1036-1043.10.1111/j.1432-2277.2007.00552.x.
27. Billing H, Giese T, Sommerer C, Zeier M, Feneberg R, Meuer S, Tönshoff B: Pharmacodynamic monitoring of cyclosporine A by NFAT-regulated gene expression and the relationship with infectious complications in pediatric renal transplant recipients. Pediatr Transplant 2010, 14:844-851.10.1111/j.1399-3046.2010.01354.x.
28. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H, European Network for Non-invasive Investigation of Large Arteries: Expert consensus document on arterial stiffness: Methodological issues and clinical applications. Eur Heart J 2006, 27:2588-2605.10.1093/eurheartj/ehl254.
29. Bahous SA, Stephan A, Barakat W, Blacher J, Asmar R, Safar ME: Aortic pulse wave velocity in renal transplant patients. Kidney Int 2004, 66:1486-1492.10.1111/j.1523-1755.2004.00912.x.
30. Seckinger J, Sommerer C, Hinkel UP, Hoffmann O, Zeier M, Schwenger V: Switch of immunosuppression from ciclosporin A to everolimus: impact on pulse wave velocity in stable de novo renal allograft recipients. J Hypertens 2008, 26:2213-2219.10.1097/HJH.0b013e32830ef940.
31. Committee for Medicinal Products for Human Use (CHMP). European Medicines Agency: Guideline on clinical investigation of immunosuppressants for solid organ transplantation. [http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003593.pdf Accessed 29 Aprile 2014]
32. Wilson PWF, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB: Prediction of coronary heart disease using risk factor categories. Circulation 1998, 97:1837-1847.10.1161/01.CIR.97.18.1837.
33. Franke GH, Reimer J, Kohnle M, Luetkes P, Maehner N, Heemann U: Quality of life in end-stage renal disease patients after successful kidney transplantation: development of the ESRD symptom checklist - transplantation module. Nephron 1999, 83:31-39.10.1159/000045470.
34. Ware J Jr, Kiosinski M, Keller SD: A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care 1996, 34:220-233.10.1097/00005650-199603000-00003.
35. Hirai T, Furusawa M, Omoto K, Ishida H, Tanabe K: Analysis of predictive and preventive factors for de novo DSA in kidney transplant recipients. Transplantation 2014, 98:443-450.10.1097/TP.0000000000000071.
36. Sommerer C, Müller-Krebs S, Schaier M, Glander P, Budde K, Schwenger V, Mikus G, Zeier M: Pharmacokinetic and pharmacodynamic analysis of enteric-coated mycophenolate sodium: limited sampling strategies and clinical outcome in renal transplant patients. Br J Clin Pharmacol 2010, 69:346-357.10.1111/j.1365-2125.2009.03612.x.
37. van Gelder T, Silva HT, de Fijter JW, Budde K, Kuypers D, Tyden G, Lohmus A, Sommerer C, Hartmann A, Le Meur Y, Oellerich M, Holt DW, Tonshoff B, Keown P, Campbell S, Mamelok RD: Comparing mycophenolate mofetil regimens for de novo renal transplant recipients: the fixed-dose concentration controlled trial. Transplantation 2008, 86:1043-1051.10.1097/TP.0b013e318186f98a.
38. Schulz KF, Altman DG, Moher D, CONSORT Group: CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ 2010, 340:c332.10.1136/bmj.c332.
39. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Struijker Boudier HA, Zanchetti A, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, et al.: Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2007, 2007:1462-1536.
40. Claes KJ, Heye S, Bammens B, Kuypers DR, Meijers B, Naesens M, Vanrenterghem Y, Evenepoel P: Aortic calcifications and arterial stiffness as predictors of cardiovascular events in incident renal transplant recipients. Transpl Int 2013, 26:973-981.
41. Verbeke F, Maréchal C, Van Laecke S, Van Biesen W, Devuyst O, Van Bortel LM, Jadoul M, Vanholder R: Aortic stiffness and central wave reflections predict outcome in renal transplant recipients. Hypertension 2011, 58:833-838.10.1161/HYPERTENSIONAHA.111.176594.