Everolimus With Reduced Calcineurin Inhibitor in Thoracic Transplant Recipients With Renal Dysfunction: A Multicenter, Randomized Trial.
(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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- author
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Transplantation
- volume
- 89
- pages
- 864 - 872
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- wos:000276807100015
- pmid:20061999
- scopus:77950952997
- pmid:20061999
- ISSN
- 1534-6080
- DOI
- 10.1097/TP.0b013e3181cbac2d
- language
- English
- LU publication?
- yes
- id
- f87974be-67c4-4daf-80c0-3a37142af1fc (old id 1541243)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/20061999?dopt=Abstract
- date added to LUP
- 2016-04-04 09:36:51
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- 2022-04-23 21:17:29
@article{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 >/=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.}},
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 = {{Lippincott Williams & Wilkins}},
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}},
doi = {{10.1097/TP.0b013e3181cbac2d}},
volume = {{89}},
year = {{2010}},
}