title: 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.
abstract: 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.).
authors.affiliation: Department of Surgery, Wright State University, Dayton, OH.
authors.forename: R B
authors.initials: RB
authors.lastname: Stevens
authors.affiliation: Department of Surgery, Wright State University, Dayton, OH.
authors.forename: L E
authors.initials: LE
authors.lastname: Wrenshall
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE.
authors.forename: C D
authors.initials: CD
authors.lastname: Miles
authors.affiliation: Department of Surgery, Wake Forest University, Winston-Salem, NC.
authors.forename: A C
authors.initials: AC
authors.lastname: Farney
authors.affiliation: Department of Surgery, University of Arizona, Tucson, AZ.
authors.forename: T
authors.initials: T
authors.lastname: Jie
authors.affiliation: Department of Surgery, Wright State University, Dayton, OH.
authors.forename: J P
authors.initials: JP
authors.lastname: Sandoz
authors.affiliation: Department of Surgery, Wright State University, Dayton, OH.
authors.forename: T H
authors.initials: TH
authors.lastname: Rigley
authors.affiliation: Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX.
authors.forename: A
authors.initials: A
authors.lastname: Osama Gaber
mesh_terms: D000328:Adult; D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000188:drug therapy* / Q000209:etiology; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011817:Rabbits; D016896:Treatment Outcome
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; C512542:thymoglobulin