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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.T

Abstract

BACKGROUND

To reduce long-term nephrotoxic calcineurin inhibitor dosage, adjunctive sirolimus or mycophenolate mofetil (MMF) was used in a 150-patient, randomized, three-armed trial in cadaveric or human leukocyte antigen non-identical living-donor first renal transplant recipients (n=50/group).

METHODS

Group A received tacrolimus and sirolimus. Target tacrolimus trough levels postoperatively were 10, 8, and 6 ng/mL at 1 month, 6 months, and 1 year, respectively. Group B received tacrolimus and MMF. Target tacrolimus trough levels were 10 and 8 ng/mL at 1 month and 1 year, with a targeted dose of MMF of 1 g twice daily. Group C received cyclosporine A (CsA) (Neoral, Novartis, Basel, Switzerland) and sirolimus with target CsA trough levels of 225 and 175 ng/mL at 1 month and 1 year. Maintenance sirolimus target trough levels were 8 ng/mL in groups A and C. Each group received daclizumab induction and methylprednisolone maintenance. This first of two companion 1-year reports details demographics, drug-dosing interactions, and rejection.

RESULTS

There were no notable differences in group demographics, but a somewhat less favorable course occurred in group C, despite higher bioavailability of sirolimus in group C versus group A (P<0.001). Acute rejection rates were lower in groups A (4%) and B (4%) combined versus group C (14%) (P=0.03). Histopathologic findings were supported by comparing perioperative with 1-year postoperative protocol biopsies.

CONCLUSIONS

This 1-year interim analysis indicates that a decreasing dosage of tacrolimus with either adjunctive sirolimus or MMF may optimize future graft survival versus a less favorable outcome using a similar algorithm with CsA and sirolimus.

Authors+Show Affiliations

Department of Surgery, Division of Transplantation, University of Miami School of Medicine, Miami, Florida 33101, USA. gciancio@med.miami.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14742989

Citation

Ciancio, Gaetano, et al. "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, vol. 77, no. 2, 2004, pp. 244-51.
Ciancio G, Burke GW, Gaynor JJ, et al. 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;77(2):244-51.
Ciancio, G., Burke, G. W., Gaynor, J. J., Mattiazzi, A., Roth, D., Kupin, W., Nicolas, M., Ruiz, P., Rosen, A., & Miller, J. (2004). 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, 77(2), 244-51.
Ciancio G, et al. 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. PubMed PMID: 14742989.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Ciancio,Gaetano, AU - Burke,George W, AU - Gaynor,Jeffrey J, AU - Mattiazzi,Adela, AU - Roth,David, AU - Kupin,Warren, AU - Nicolas,Maud, AU - Ruiz,Phillip, AU - Rosen,Anne, AU - Miller,Joshua, PY - 2004/1/27/pubmed PY - 2004/2/28/medline PY - 2004/1/27/entrez SP - 244 EP - 51 JF - Transplantation JO - Transplantation VL - 77 IS - 2 N2 - BACKGROUND: To reduce long-term nephrotoxic calcineurin inhibitor dosage, adjunctive sirolimus or mycophenolate mofetil (MMF) was used in a 150-patient, randomized, three-armed trial in cadaveric or human leukocyte antigen non-identical living-donor first renal transplant recipients (n=50/group). METHODS: Group A received tacrolimus and sirolimus. Target tacrolimus trough levels postoperatively were 10, 8, and 6 ng/mL at 1 month, 6 months, and 1 year, respectively. Group B received tacrolimus and MMF. Target tacrolimus trough levels were 10 and 8 ng/mL at 1 month and 1 year, with a targeted dose of MMF of 1 g twice daily. Group C received cyclosporine A (CsA) (Neoral, Novartis, Basel, Switzerland) and sirolimus with target CsA trough levels of 225 and 175 ng/mL at 1 month and 1 year. Maintenance sirolimus target trough levels were 8 ng/mL in groups A and C. Each group received daclizumab induction and methylprednisolone maintenance. This first of two companion 1-year reports details demographics, drug-dosing interactions, and rejection. RESULTS: There were no notable differences in group demographics, but a somewhat less favorable course occurred in group C, despite higher bioavailability of sirolimus in group C versus group A (P<0.001). Acute rejection rates were lower in groups A (4%) and B (4%) combined versus group C (14%) (P=0.03). Histopathologic findings were supported by comparing perioperative with 1-year postoperative protocol biopsies. CONCLUSIONS: This 1-year interim analysis indicates that a decreasing dosage of tacrolimus with either adjunctive sirolimus or MMF may optimize future graft survival versus a less favorable outcome using a similar algorithm with CsA and sirolimus. SN - 0041-1337 UR - https://www.unboundmedicine.com/medline/citation/14742989/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_ L2 - http://dx.doi.org/10.1097/01.TP.0000101290.20629.DC DB - PRIME DP - Unbound Medicine ER -