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
A previous nonblinded, randomized, single center renal transplantation trial of single dose rabbit anti thymocyte 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 <1.73% of continued enrollment producing a significant difference (futility analysis) leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point 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.
American journal of transplantation official journal of the American Society of Transplantation and the American Society of Transplant Surgeons