Lessons Learned: Early Termination of a Randomized Trial of Calcineurin Inhibitor and Corticosteroid Avoidance Using Belatacept

K. A. Newell, A. K. Mehta, C. P. Larsen, P. G. Stock, A. B. Farris, S. G. Mehta, D. Ikle, B. Armstrong, Y. Morrison, N. Bridges, M. Robien, R. B. Mannon

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2712-2719
Number of pages8
JournalAmerican Journal of Transplantation
Volume17
Issue number10
DOIs
StatePublished - Oct 2017

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Keywords

  • fusion proteins and monoclonal antibodies: belatacept
  • immunosuppressant
  • immunosuppression/immune modulation
  • kidney transplantation/nephrology
  • rejection
  • translational research/science

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

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, 17(10), 2712-2719. https://doi.org/10.1111/ajt.14377