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Everolimus Versus Mycophenolate Mofetil De Novo After Lung Transplantation: A Prospective, Randomized, Open-Label Trial.
Am J Transplant 2016; 16(11):3171-3180AJ

Abstract

The role of mammalian target of rapamycin (mTOR) inhibitors in de novo immunosuppression after lung transplantation is not well defined. We compared Everolimus versus mycophenolate mofetil in an investigator-initiated single-center trial in Hannover, Germany. A total of 190 patients were randomly assigned 1:1 on day 28 posttransplantation to mycophenolate mofetil (MMF) or Everolimus combined with cyclosporine A (CsA) and steroids. Patients were followed up for 2 years. The primary endpoint was freedom from bronchiolitis obliterans syndrome (BOS). The secondary endpoints were incidence of acute rejections, infections, treatment failure and kidney function. BOS-free survival in intention-to-treat (ITT) analysis was similar in both groups (p = 0.174). The study protocol was completed by 51% of enrolled patients. The per-protocol analysis shows incidence of bronchiolitis obliterans syndrome (BOS): 1/43 in the Everolimus group and 8/54 in the MMF group (p = 0.041). Less biopsy-proven acute rejection (AR) (p = 0.005), cytomegalovirus (CMV) antigenemia (p = 0.005) and lower respiratory tract infection (p = 0.003) and no leucopenia were seen in the Everolimus group. The glomerular filtration rate (GFR) decreased in both groups about 50% within 6 months. Due to a high withdrawal rate, the study was underpowered to prove a difference in BOS-free survival. The dropout rate was more pronounced in the Everolimus group. Secondary endpoints indicate potential advantages of Everolimus-based protocols but also a potentially higher rate of drug-related serious adverse events.

Authors+Show Affiliations

Richard DeVos Heart & Lung Transplant Program, Frederik Meijer Heart & Vascular Institute, Grand Rapids, MI. strueber@msu.edu.Department of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany. German Centre of Lung Research (DZL/BREATH), Hannover Medical School, Hannover, Germany.Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany.Department of Heart and Lung Transplantation/VAD, Royal Brompton & Harefield NHS Foundation Trust, London, United Kingdom.Department of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.German Centre of Lung Research (DZL/BREATH), Hannover Medical School, Hannover, Germany. Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany.Department of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany. German Centre of Lung Research (DZL/BREATH), Hannover Medical School, Hannover, Germany.German Centre of Lung Research (DZL/BREATH), Hannover Medical School, Hannover, Germany. Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany.

Pub Type(s)

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

Language

eng

PubMed ID

27104933

Citation

Strueber, M, et al. "Everolimus Versus Mycophenolate Mofetil De Novo After Lung Transplantation: a Prospective, Randomized, Open-Label Trial." American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, vol. 16, no. 11, 2016, pp. 3171-3180.
Strueber M, Warnecke G, Fuge J, et al. Everolimus Versus Mycophenolate Mofetil De Novo After Lung Transplantation: A Prospective, Randomized, Open-Label Trial. Am J Transplant. 2016;16(11):3171-3180.
Strueber, M., Warnecke, G., Fuge, J., Simon, A. R., Zhang, R., Welte, T., ... Gottlieb, J. (2016). Everolimus Versus Mycophenolate Mofetil De Novo After Lung Transplantation: A Prospective, Randomized, Open-Label Trial. American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 16(11), pp. 3171-3180. doi:10.1111/ajt.13835.
Strueber M, et al. Everolimus Versus Mycophenolate Mofetil De Novo After Lung Transplantation: a Prospective, Randomized, Open-Label Trial. Am J Transplant. 2016;16(11):3171-3180. PubMed PMID: 27104933.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Everolimus Versus Mycophenolate Mofetil De Novo After Lung Transplantation: A Prospective, Randomized, Open-Label Trial. AU - Strueber,M, AU - Warnecke,G, AU - Fuge,J, AU - Simon,A R, AU - Zhang,R, AU - Welte,T, AU - Haverich,A, AU - Gottlieb,J, Y1 - 2016/06/15/ PY - 2015/07/14/received PY - 2016/03/27/revised PY - 2016/04/16/accepted PY - 2016/10/28/pubmed PY - 2017/11/1/medline PY - 2016/4/23/entrez KW - antiproliferative agent: mycophenolate mofetil (MMF) KW - bronchiolitis obliterans (BOS) KW - calcineurin inhibitor: cyclosporine A (CsA) KW - clinical research/practice KW - clinical trial KW - immunosuppressant KW - immunosuppression/immune modulation KW - lung transplantation/pulmonology KW - mechanistic target of rapamycin (mTOR) KW - pharmacology SP - 3171 EP - 3180 JF - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons JO - Am. J. Transplant. VL - 16 IS - 11 N2 - The role of mammalian target of rapamycin (mTOR) inhibitors in de novo immunosuppression after lung transplantation is not well defined. We compared Everolimus versus mycophenolate mofetil in an investigator-initiated single-center trial in Hannover, Germany. A total of 190 patients were randomly assigned 1:1 on day 28 posttransplantation to mycophenolate mofetil (MMF) or Everolimus combined with cyclosporine A (CsA) and steroids. Patients were followed up for 2 years. The primary endpoint was freedom from bronchiolitis obliterans syndrome (BOS). The secondary endpoints were incidence of acute rejections, infections, treatment failure and kidney function. BOS-free survival in intention-to-treat (ITT) analysis was similar in both groups (p = 0.174). The study protocol was completed by 51% of enrolled patients. The per-protocol analysis shows incidence of bronchiolitis obliterans syndrome (BOS): 1/43 in the Everolimus group and 8/54 in the MMF group (p = 0.041). Less biopsy-proven acute rejection (AR) (p = 0.005), cytomegalovirus (CMV) antigenemia (p = 0.005) and lower respiratory tract infection (p = 0.003) and no leucopenia were seen in the Everolimus group. The glomerular filtration rate (GFR) decreased in both groups about 50% within 6 months. Due to a high withdrawal rate, the study was underpowered to prove a difference in BOS-free survival. The dropout rate was more pronounced in the Everolimus group. Secondary endpoints indicate potential advantages of Everolimus-based protocols but also a potentially higher rate of drug-related serious adverse events. SN - 1600-6143 UR - https://www.unboundmedicine.com/medline/citation/27104933/Everolimus_Versus_Mycophenolate_Mofetil_De_Novo_After_Lung_Transplantation:_A_Prospective_Randomized_Open_Label_Trial_ L2 - https://doi.org/10.1111/ajt.13835 DB - PRIME DP - Unbound Medicine ER -