RESULTS OF THE DOUBLE-BLIND, RANDOMIZED, MULTICENTER, PHASE-III CLINICAL-TRIAL OF THYMOGLOBULIN VERSUS ATGAM IN THE TREATMENT OF ACUTE GRAFT-REJECTION EPISODES AFTER RENAL-TRANSPLANTATION

Background Thymoglobulin, a rabbit anti-human thymocyte globulin, was compared with Atgam, a horse anti-human thymocyte globulin for the tre atment of acute rejection after renal transplantation. Methods. A mult icenter, double-blind, randomized trial with enrollment stratification based on standardized histology (Banff grading) was conducted. Subjec ts received 7-14 days of Thymoglobulin (1.5 mg/kg/ day) or Atgam (15 m g/kg/day). The primary end point was rejection reversal (return of ser um creatinine level to or below the day 0 baseline value). Results. A total of 163 patients were enrolled at 25 transplant centers in the Un ited States. No differences in demographics or transplant characterist ics were noted. Intent-to-treat analysis demonstrated that Thymoglobul in had a higher rejection reversal rate than Atgam (88% versus 76%, P= 0.027, primary end point). Day 30 graft survival rates (Thymoglobulin 94% and Atgam 90%, P=0.17), day 30 serum creatinine levels as a percen tage of baseline (Thymoglobulin 72% and Atgam 80%; P=0.43), and improv ement in posttreatment biopsy results (Thymoglobulin 65% and Atgam 50% ; P=0.15) were not statistically different. T-cell depletion was maint ained more effectively with Thymoglobulin than Atgam both at the end o f therapy (P=0.001) and at day 30 (P=0.016). Recurrent rejection, at 9 0 days after therapy, occurred less frequently with Thymoglobulin (17% ) versus Atgam (36%) (P=0.011). A similar incidence of adverse events, posttherapy infections, and 1-year patient and graft survival rates w ere observed with both treatments. Conclusions. Thymoglobulin was foun d to be superior to Atgam in reversing acute rejection and preventing recurrent rejection after therapy in renal transplant recipients.