American Journal of Transplantation 2016; 16: 1858–1867 Wiley Periodicals Inc.
© Copyright 2016 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of the American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/ajt.13659
A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation R. B. Stevens1,*, L. E. Wrenshall1, C. D. Miles2, A. C. Farney3, T. Jie4, J. P. Sandoz1, T. H. Rigley1 and A. Osama Gaber5 1
Department of Surgery, Wright State University, Dayton, OH 2 Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 3 Department of Surgery, Wake Forest University, Winston-Salem, NC 4 Department of Surgery, University of Arizona, Tucson, AZ 5 Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX *Corresponding author: R. Brian Stevens,
[email protected] This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD-rATG induction to be noninferior to DD-rATG induction in early tolerability and equivalent in 12-month safety. (Clinical Trials.gov #NCT00906204.) Abbreviations: BID, twice daily; CMV, cytomegalovirus; DD-rATG, divided-dose rabbit anti–thymocyte globulin; DGF, delayed graft function; FIO2, fraction of inspired oxygen; MMF, mycophenolate mofetil; MPA, mycophenolic acid; PO, orally; PRA, panel reactive antibody; rATG, rabbit anti–thymocyte globulin; SDrATG, single-dose rabbit anti–thymocyte globulin; SEM, standard error of the mean Received 09 October 2015, revised 11 November 2015 and accepted for publication 29 November 2015
Introduction A previous nonblinded, randomized, single-center renal transplantation trial of single-dose rabbit antithymocyte globulin induction (SD-rATG) showed improved efficacy compared with conventional divided-dose (DD-rATG) administration. The present multicenter, double-blind/double-dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD-rATG versus DD-rATG induction for noninferiority in early (7-day) safety and tolerability. Ninety-five patients (randomized 1:1) received 6 mg/kg SD-rATG or 1.5 mg/kg/dose DD-rATG, with tacrolimus-mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12-month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD-rATG induction (p = 0.6), and a conditional probability of
