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Everolimus With Reduced Calcineurin Inhibitor in Thoracic Transplant Recipients With Renal Dysfunction: A Multicenter, Randomized Trial.

Gullestad, Lars; Iversen, Martin; Mortensen, Svend-Aage; Eiskjær, Hans; Riise, Gerdt C; Mared, Lena LU ; Bjørtuft, Oystein; Ekmehag, Björn LU ; Jansson, Kjell and Simonsen, Svein, et al. (2010) In Transplantation 89. p.864-872
Abstract
BACKGROUND.: The proliferation signal inhibitor everolimus offers the potential to reduce calcineurin inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking. METHODS.: In a 12-month, open-labeled, multicenter study, maintenance thoracic transplant patients (glomerular filtration rate >/=20 mL/min/1.73m and <90 mL/min/1.73 m) >1 year posttransplant were randomized to continue their current CNI-based immunosuppression or start everolimus with predefined CNI exposure reduction. RESULTS.: Two hundred eighty-two patients were randomized (140 everolimus, 142 controls; 190 heart, 92 lung transplants). From baseline to month 12, mean cyclosporine and... (More)
BACKGROUND.: The proliferation signal inhibitor everolimus offers the potential to reduce calcineurin inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking. METHODS.: In a 12-month, open-labeled, multicenter study, maintenance thoracic transplant patients (glomerular filtration rate >/=20 mL/min/1.73m and <90 mL/min/1.73 m) >1 year posttransplant were randomized to continue their current CNI-based immunosuppression or start everolimus with predefined CNI exposure reduction. RESULTS.: Two hundred eighty-two patients were randomized (140 everolimus, 142 controls; 190 heart, 92 lung transplants). From baseline to month 12, mean cyclosporine and tacrolimus trough levels in the everolimus cohort decreased by 57% and 56%, respectively. The primary endpoint, mean change in measured glomerular filtration rate from baseline to month 12, was 4.6 mL/min with everolimus and -0.5 mL/min in controls (P<0.0001). Everolimus-treated heart and lung transplant patients in the lowest tertile for time posttransplant exhibited mean increases of 7.8 mL/min and 4.9 mL/min, respectively. Biopsy-proven treated acute rejection occurred in six everolimus and four control heart transplant patients (P=0.54). In total, 138 everolimus patients (98.6%) and 127 control patients (89.4%) experienced one or more adverse event (P=0.002). Serious adverse events occurred in 66 everolimus patients (46.8%) and 44 controls (31.0%) (P=0.02). CONCLUSION.: Introduction of everolimus with CNI reduction offers a significant improvement in renal function in maintenance heart and lung transplant recipients. The greatest benefit is observed in patients with a shorter time since transplantation. (Less)
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published
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Transplantation
volume
89
pages
864 - 872
publisher
Lippincott Williams & Wilkins
external identifiers
  • WOS:000276807100015
  • PMID:20061999
  • Scopus:77950952997
ISSN
1534-6080
DOI
10.1097/TP.0b013e3181cbac2d
language
English
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yes
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f87974be-67c4-4daf-80c0-3a37142af1fc (old id 1541243)
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http://www.ncbi.nlm.nih.gov/pubmed/20061999?dopt=Abstract
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2010-02-02 12:06:58
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2016-11-13 04:29:36
@misc{f87974be-67c4-4daf-80c0-3a37142af1fc,
  abstract     = {BACKGROUND.: The proliferation signal inhibitor everolimus offers the potential to reduce calcineurin inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking. METHODS.: In a 12-month, open-labeled, multicenter study, maintenance thoracic transplant patients (glomerular filtration rate &gt;/=20 mL/min/1.73m and &lt;90 mL/min/1.73 m) &gt;1 year posttransplant were randomized to continue their current CNI-based immunosuppression or start everolimus with predefined CNI exposure reduction. RESULTS.: Two hundred eighty-two patients were randomized (140 everolimus, 142 controls; 190 heart, 92 lung transplants). From baseline to month 12, mean cyclosporine and tacrolimus trough levels in the everolimus cohort decreased by 57% and 56%, respectively. The primary endpoint, mean change in measured glomerular filtration rate from baseline to month 12, was 4.6 mL/min with everolimus and -0.5 mL/min in controls (P&lt;0.0001). Everolimus-treated heart and lung transplant patients in the lowest tertile for time posttransplant exhibited mean increases of 7.8 mL/min and 4.9 mL/min, respectively. Biopsy-proven treated acute rejection occurred in six everolimus and four control heart transplant patients (P=0.54). In total, 138 everolimus patients (98.6%) and 127 control patients (89.4%) experienced one or more adverse event (P=0.002). Serious adverse events occurred in 66 everolimus patients (46.8%) and 44 controls (31.0%) (P=0.02). CONCLUSION.: Introduction of everolimus with CNI reduction offers a significant improvement in renal function in maintenance heart and lung transplant recipients. The greatest benefit is observed in patients with a shorter time since transplantation.},
  author       = {Gullestad, Lars and Iversen, Martin and Mortensen, Svend-Aage and Eiskjær, Hans and Riise, Gerdt C and Mared, Lena and Bjørtuft, Oystein and Ekmehag, Björn and Jansson, Kjell and Simonsen, Svein and Gude, Einar and Rundqvist, Bengt and Fagertun, Hans E and Solbu, Dag and Bergh, Claes-Håkan},
  issn         = {1534-6080},
  language     = {eng},
  pages        = {864--872},
  publisher    = {ARRAY(0xa8e37d8)},
  series       = {Transplantation},
  title        = {Everolimus With Reduced Calcineurin Inhibitor in Thoracic Transplant Recipients With Renal Dysfunction: A Multicenter, Randomized Trial.},
  url          = {http://dx.doi.org/10.1097/TP.0b013e3181cbac2d},
  volume       = {89},
  year         = {2010},
}