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Early Conversion From Calcineurin Inhibitor- to Everolimus-Based Therapy Following Kidney Transplantation: Results of the Randomized ELEVATE Trial

Title: Early Conversion From Calcineurin Inhibitor- to Everolimus-Based Therapy Following Kidney Transplantation: Results of the Randomized ELEVATE Trial
Authors: de Fijter, J.W.; Holdaas, H.; Oyen, O.; Sanders, J-S.; Sundar, S.; Bemelman, F.J.; Sommerer, C.; Pascual, J.; Avihingsanon, Y.; Pongskul, C.; Oppenheimer, F.; Toselli, L.; Russ, G.; Wang, Z.; Lopez, P.; Kochuparampil, J.; Cruzado, J.M.; van der Giet, M.; ELEVATE Study Group
Contributors: Kuypers, Dirk
Source: ISSN:1600-6135 ; ISSN:1600-6143 ; American Journal Of Transplantation, vol. 17 (7), (1853-1867.
Publisher Information: Wiley
Publication Year: 2017
Subject Terms: Science & Technology; Life Sciences & Biomedicine; Surgery; Transplantation; DONOR-SPECIFIC ANTIBODIES; LEFT-VENTRICULAR MASS; RENAL-TRANSPLANTATION; CARDIAC-HYPERTROPHY; PRESSURE-OVERLOAD; MAMMALIAN TARGET; HLA ANTIBODIES; RECIPIENTS; CYCLOSPORINE; SIROLIMUS; RENAL-FUNCTION; EVOLUTION; calcineurin inhibitor (CNI); cardiovascular disease; clinical research/practice; clinical trial; immunosuppressant; immunosuppression/immune modulation; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; mechanistic target of rapamycin: everolimus; Everolimus; Female; Follow-Up Studies; Glomerular Filtration Rate; Graft Rejection
Description: In a 24-month, multicenter, open-label, randomized trial, 715 de novo kidney transplant recipients were randomized at 10-14 weeks to convert to everolimus (n = 359) or remain on standard calcineurin inhibitor (CNI) therapy (n = 356; 231 tacrolimus; 125 cyclosporine), all with mycophenolic acid and steroids. The primary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, was similar for everolimus versus CNI: mean (standard error) 0.3(1.5) mL/min/1.732 versus -1.5(1.5) mL/min/1.732 (p = 0.116). Biopsy-proven acute rejection (BPAR) at month 12 was more frequent under everolimus versus CNI overall (9.7% vs. 4.8%, p = 0.014) and versus tacrolimus-treated patients (2.6%, p < 0.001) but similar to cyclosporine-treated patients (8.8%, p = 0.755). Reporting on de novo donor-specific antibodies (DSA) was limited but suggested more frequent anti-HLA Class I DSA under everolimus. Change in left ventricular mass index was similar. Discontinuation due to adverse events was more frequent with everolimus (23.6%) versus CNI (8.4%). In conclusion, conversion to everolimus at 10-14 weeks posttransplant was associated with renal function similar to that with standard therapy overall. Rates of BPAR were low in all groups, but lower with tacrolimus than everolimus. ; sponsorship: The study was funded by Novartis Pharma AG. Funding for a freelance medical writer was also provided by Novartis Pharma AG. (Novartis Pharma AG) ; status: Published
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: https://lirias.kuleuven.be/handle/123456789/629631; https://doi.org/10.1111/ajt.14186; https://pubmed.ncbi.nlm.nih.gov/28027625
DOI: 10.1111/ajt.14186
Availability: https://lirias.kuleuven.be/handle/123456789/629631; https://lirias.kuleuven.be/retrieve/39f7a32a-ba5d-45ec-a6f4-be8cd5db717f; https://doi.org/10.1111/ajt.14186; https://pubmed.ncbi.nlm.nih.gov/28027625
Rights: info:eu-repo/semantics/openAccess ; public
Accession Number: edsbas.3A84A761
Database: BASE