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Lessons Learned: Early Termination of a Randomized Trial of Calcineurin Inhibitor and Corticosteroid Avoidance Using Belatacept.
Am J Transplant. 2017 Oct; 17(10):2712-2719.AJ

Abstract

The intent of this National Institutes of Health-sponsored study was to compare a belatacept-based immunosuppressive regimen with a maintenance regimen of tacrolimus and mycophenolate. Nineteen primary, Epstein-Barr virus-immune renal transplant recipients with a negative cross-match were randomized to one of three groups. All patient groups received perioperative steroids and maintenance mycophenolate mofetil. Patients in groups 1 and 2 were induced with alemtuzumab and maintained on tacrolimus or belatacept, respectively. Patients in group 3 were induced with basiliximab, received 3 mo of tacrolimus, and maintained on belatacept. There was one death with a functioning allograft due to endocarditis (group 1). There were three graft losses due to vascular thrombosis (all group 2) and one graft loss due to glomerular disease (group 1). Biopsy-proven acute cellular rejection was more frequent in the belatacept-treated groups, with 10 treated episodes in seven participants compared with one episode in group 1; however, estimated GFR was similar between groups at week 52. There were no episodes of posttransplant lymphoproliferative disorder or opportunistic infections in any group. Protocol enrollment was halted prematurely because of a high rate of serious adverse events. Such negative outcomes pose challenges to clinical investigators, who ultimately must weigh the risks and benefits in randomized trials.

Authors+Show Affiliations

Department of Surgery, Emory University School of Medicine, Atlanta, GA.Department of Surgery, Emory University School of Medicine, Atlanta, GA. Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA.Department of Surgery, Emory University School of Medicine, Atlanta, GA.Division of Transplantation, Department of Surgery, University of California San Francisco, San Francisco, CA.Department of Surgery, Emory University School of Medicine, Atlanta, GA.Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.Rho, Chapel Hill, NC.Rho, Chapel Hill, NC.Transplantation Branch, National Institute Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.Transplantation Branch, National Institute Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.Transplantation Branch, National Institute Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

28556519

Citation

Newell, K A., et al. "Lessons Learned: Early Termination of a Randomized Trial of Calcineurin Inhibitor and Corticosteroid Avoidance Using Belatacept." American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, vol. 17, no. 10, 2017, pp. 2712-2719.
Newell KA, Mehta AK, Larsen CP, et al. Lessons Learned: Early Termination of a Randomized Trial of Calcineurin Inhibitor and Corticosteroid Avoidance Using Belatacept. Am J Transplant. 2017;17(10):2712-2719.
Newell, K. A., Mehta, A. K., Larsen, C. P., Stock, P. G., Farris, A. B., Mehta, S. G., Ikle, D., Armstrong, B., Morrison, Y., Bridges, N., Robien, M., & Mannon, R. B. (2017). Lessons Learned: Early Termination of a Randomized Trial of Calcineurin Inhibitor and Corticosteroid Avoidance Using Belatacept. American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 17(10), 2712-2719. https://doi.org/10.1111/ajt.14377
Newell KA, et al. Lessons Learned: Early Termination of a Randomized Trial of Calcineurin Inhibitor and Corticosteroid Avoidance Using Belatacept. Am J Transplant. 2017;17(10):2712-2719. PubMed PMID: 28556519.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lessons Learned: Early Termination of a Randomized Trial of Calcineurin Inhibitor and Corticosteroid Avoidance Using Belatacept. AU - Newell,K A, AU - Mehta,A K, AU - Larsen,C P, AU - Stock,P G, AU - Farris,A B, AU - Mehta,S G, AU - Ikle,D, AU - Armstrong,B, AU - Morrison,Y, AU - Bridges,N, AU - Robien,M, AU - Mannon,R B, Y1 - 2017/07/03/ PY - 2016/12/20/received PY - 2017/04/26/revised PY - 2017/05/21/accepted PY - 2017/5/31/pubmed PY - 2018/6/15/medline PY - 2017/5/31/entrez KW - fusion proteins and monoclonal antibodies: belatacept KW - immunosuppressant KW - immunosuppression/immune modulation KW - kidney transplantation/nephrology KW - rejection KW - translational research/science SP - 2712 EP - 2719 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 - 17 IS - 10 N2 - The intent of this National Institutes of Health-sponsored study was to compare a belatacept-based immunosuppressive regimen with a maintenance regimen of tacrolimus and mycophenolate. Nineteen primary, Epstein-Barr virus-immune renal transplant recipients with a negative cross-match were randomized to one of three groups. All patient groups received perioperative steroids and maintenance mycophenolate mofetil. Patients in groups 1 and 2 were induced with alemtuzumab and maintained on tacrolimus or belatacept, respectively. Patients in group 3 were induced with basiliximab, received 3 mo of tacrolimus, and maintained on belatacept. There was one death with a functioning allograft due to endocarditis (group 1). There were three graft losses due to vascular thrombosis (all group 2) and one graft loss due to glomerular disease (group 1). Biopsy-proven acute cellular rejection was more frequent in the belatacept-treated groups, with 10 treated episodes in seven participants compared with one episode in group 1; however, estimated GFR was similar between groups at week 52. There were no episodes of posttransplant lymphoproliferative disorder or opportunistic infections in any group. Protocol enrollment was halted prematurely because of a high rate of serious adverse events. Such negative outcomes pose challenges to clinical investigators, who ultimately must weigh the risks and benefits in randomized trials. SN - 1600-6143 UR - https://www.unboundmedicine.com/medline/citation/28556519/Lessons_Learned:_Early_Termination_of_a_Randomized_Trial_of_Calcineurin_Inhibitor_and_Corticosteroid_Avoidance_Using_Belatacept_ L2 - https://doi.org/10.1111/ajt.14377 DB - PRIME DP - Unbound Medicine ER -