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

Osama O. Gaber, M. Roy First, Raymond J. Tesi, Robert S. Gaston, Robert Mendez, Laura L Mulloy, Jimmy A. Light, Lillian W. Gaber, Elizabeth Squiers, Rodney J. Taylor, John F. Neylan, Robert W. Steiner, Stuart Knechtle, Douglas J. Norman, Fuad Shihab, Giacomo Basadonna, Daniel C. Brennan, Ernest E. Hodge, Barry D. Kahan, Lawrence KahanaSteven Steinberg, E. Steve Woodle, Laurence Chan, John M. Ham, Robert J. Stratta, Erik Wahlstrom, Kathleen R. Lamborn, H. Rossiter Horn, Hana Berger Moran, Philippe Pouletty, Timothy J. Schroeder

Research output: Contribution to journalArticle

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Abstract

Background. Thymoglobulin, a rabbit anti-human thymocyte globulin, was compared with Atgam, a horse anti-human thymocyte globulin for the treatment of acute rejection after renal transplantation. Methods. A multicenter, double-blind, randomized trial with enrollment stratification based on standardized histology (Banff grading) was conducted. Subjects received 7-14 days of Thymoglobulin (1.5 mg/kg/day) or Atgam (15 mg/kg/day). The primary end point was rejection reversal (return of serum creatinine level to or below the day 0 baseline value). Results. A total of 163 patients were enrolled at 25 transplant centers in the United States. No differences in demographics or transplant characteristics were noted. Intent-to-treat analysis demonstrated that Thymoglobulin 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 percentage of baseline (Thymoglobulin 72% and At-gam 80%; P=0.43), and improvement in posttreatment biopsy results (Thymoglobulin 65% and Atgam 50%; P=0.15) were not statistically different. T-cell depletion was maintained more effectively with Thymoglobulin than Atgam both at the end of therapy (P=0.001) and at day 30 (P=0.016). Recurrent rejection, at 90 days after therapy, occurred less frequently with Thymoglobulin (17%) versus Atgam (36%) (P=O.011). A similar incidence of adverse events, post-therapy infections, and 1-year patient and graft survival rates were observed with both treatments. Conclusions. Thymoglobulin was found to be superior to Atgam in reversing acute rejection and preventing recurrent rejection after therapy in renal transplant recipients.

Original languageEnglish (US)
Pages (from-to)29-37
Number of pages9
JournalTransplantation
Volume66
Issue number1
DOIs
StatePublished - Jul 15 1998
Externally publishedYes

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Phase III Clinical Trials
Graft Rejection
Kidney Transplantation
Antilymphocyte Serum
Therapeutics
Graft Survival
Creatinine
Survival Rate
Transplants
thymoglobulin
Serum
Horses
Histology
Demography
Rabbits
T-Lymphocytes
Kidney
Biopsy

ASJC Scopus subject areas

  • Transplantation

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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. / Gaber, Osama O.; First, M. Roy; Tesi, Raymond J.; Gaston, Robert S.; Mendez, Robert; Mulloy, Laura L; Light, Jimmy A.; Gaber, Lillian W.; Squiers, Elizabeth; Taylor, Rodney J.; Neylan, John F.; Steiner, Robert W.; Knechtle, Stuart; Norman, Douglas J.; Shihab, Fuad; Basadonna, Giacomo; Brennan, Daniel C.; Hodge, Ernest E.; Kahan, Barry D.; Kahana, Lawrence; Steinberg, Steven; Woodle, E. Steve; Chan, Laurence; Ham, John M.; Stratta, Robert J.; Wahlstrom, Erik; Lamborn, Kathleen R.; Horn, H. Rossiter; Moran, Hana Berger; Pouletty, Philippe; Schroeder, Timothy J.

In: Transplantation, Vol. 66, No. 1, 15.07.1998, p. 29-37.

Research output: Contribution to journalArticle

Gaber, OO, First, MR, Tesi, RJ, Gaston, RS, Mendez, R, Mulloy, LL, Light, JA, Gaber, LW, Squiers, E, Taylor, RJ, Neylan, JF, Steiner, RW, Knechtle, S, Norman, DJ, Shihab, F, Basadonna, G, Brennan, DC, Hodge, EE, Kahan, BD, Kahana, L, Steinberg, S, Woodle, ES, Chan, L, Ham, JM, Stratta, RJ, Wahlstrom, E, Lamborn, KR, Horn, HR, Moran, HB, Pouletty, P & Schroeder, TJ 1998, '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', Transplantation, vol. 66, no. 1, pp. 29-37. https://doi.org/10.1097/00007890-199807150-00005
Gaber, Osama O. ; First, M. Roy ; Tesi, Raymond J. ; Gaston, Robert S. ; Mendez, Robert ; Mulloy, Laura L ; Light, Jimmy A. ; Gaber, Lillian W. ; Squiers, Elizabeth ; Taylor, Rodney J. ; Neylan, John F. ; Steiner, Robert W. ; Knechtle, Stuart ; Norman, Douglas J. ; Shihab, Fuad ; Basadonna, Giacomo ; Brennan, Daniel C. ; Hodge, Ernest E. ; Kahan, Barry D. ; Kahana, Lawrence ; Steinberg, Steven ; Woodle, E. Steve ; Chan, Laurence ; Ham, John M. ; Stratta, Robert J. ; Wahlstrom, Erik ; Lamborn, Kathleen R. ; Horn, H. Rossiter ; Moran, Hana Berger ; Pouletty, Philippe ; Schroeder, Timothy J. / 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. In: Transplantation. 1998 ; Vol. 66, No. 1. pp. 29-37.
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abstract = "Background. Thymoglobulin, a rabbit anti-human thymocyte globulin, was compared with Atgam, a horse anti-human thymocyte globulin for the treatment of acute rejection after renal transplantation. Methods. A multicenter, double-blind, randomized trial with enrollment stratification based on standardized histology (Banff grading) was conducted. Subjects received 7-14 days of Thymoglobulin (1.5 mg/kg/day) or Atgam (15 mg/kg/day). The primary end point was rejection reversal (return of serum creatinine level to or below the day 0 baseline value). Results. A total of 163 patients were enrolled at 25 transplant centers in the United States. No differences in demographics or transplant characteristics were noted. Intent-to-treat analysis demonstrated that Thymoglobulin 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 percentage of baseline (Thymoglobulin 72{\%} and At-gam 80{\%}; P=0.43), and improvement in posttreatment biopsy results (Thymoglobulin 65{\%} and Atgam 50{\%}; P=0.15) were not statistically different. T-cell depletion was maintained more effectively with Thymoglobulin than Atgam both at the end of therapy (P=0.001) and at day 30 (P=0.016). Recurrent rejection, at 90 days after therapy, occurred less frequently with Thymoglobulin (17{\%}) versus Atgam (36{\%}) (P=O.011). A similar incidence of adverse events, post-therapy infections, and 1-year patient and graft survival rates were observed with both treatments. Conclusions. Thymoglobulin was found to be superior to Atgam in reversing acute rejection and preventing recurrent rejection after therapy in renal transplant recipients.",
author = "Gaber, {Osama O.} and First, {M. Roy} and Tesi, {Raymond J.} and Gaston, {Robert S.} and Robert Mendez and Mulloy, {Laura L} and Light, {Jimmy A.} and Gaber, {Lillian W.} and Elizabeth Squiers and Taylor, {Rodney J.} and Neylan, {John F.} and Steiner, {Robert W.} and Stuart Knechtle and Norman, {Douglas J.} and Fuad Shihab and Giacomo Basadonna and Brennan, {Daniel C.} and Hodge, {Ernest E.} and Kahan, {Barry D.} and Lawrence Kahana and Steven Steinberg and Woodle, {E. Steve} and Laurence Chan and Ham, {John M.} and Stratta, {Robert J.} and Erik Wahlstrom and Lamborn, {Kathleen R.} and Horn, {H. Rossiter} and Moran, {Hana Berger} and Philippe Pouletty and Schroeder, {Timothy J.}",
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T1 - 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

AU - Gaber, Osama O.

AU - First, M. Roy

AU - Tesi, Raymond J.

AU - Gaston, Robert S.

AU - Mendez, Robert

AU - Mulloy, Laura L

AU - Light, Jimmy A.

AU - Gaber, Lillian W.

AU - Squiers, Elizabeth

AU - Taylor, Rodney J.

AU - Neylan, John F.

AU - Steiner, Robert W.

AU - Knechtle, Stuart

AU - Norman, Douglas J.

AU - Shihab, Fuad

AU - Basadonna, Giacomo

AU - Brennan, Daniel C.

AU - Hodge, Ernest E.

AU - Kahan, Barry D.

AU - Kahana, Lawrence

AU - Steinberg, Steven

AU - Woodle, E. Steve

AU - Chan, Laurence

AU - Ham, John M.

AU - Stratta, Robert J.

AU - Wahlstrom, Erik

AU - Lamborn, Kathleen R.

AU - Horn, H. Rossiter

AU - Moran, Hana Berger

AU - Pouletty, Philippe

AU - Schroeder, Timothy J.

PY - 1998/7/15

Y1 - 1998/7/15

N2 - Background. Thymoglobulin, a rabbit anti-human thymocyte globulin, was compared with Atgam, a horse anti-human thymocyte globulin for the treatment of acute rejection after renal transplantation. Methods. A multicenter, double-blind, randomized trial with enrollment stratification based on standardized histology (Banff grading) was conducted. Subjects received 7-14 days of Thymoglobulin (1.5 mg/kg/day) or Atgam (15 mg/kg/day). The primary end point was rejection reversal (return of serum creatinine level to or below the day 0 baseline value). Results. A total of 163 patients were enrolled at 25 transplant centers in the United States. No differences in demographics or transplant characteristics were noted. Intent-to-treat analysis demonstrated that Thymoglobulin 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 percentage of baseline (Thymoglobulin 72% and At-gam 80%; P=0.43), and improvement in posttreatment biopsy results (Thymoglobulin 65% and Atgam 50%; P=0.15) were not statistically different. T-cell depletion was maintained more effectively with Thymoglobulin than Atgam both at the end of therapy (P=0.001) and at day 30 (P=0.016). Recurrent rejection, at 90 days after therapy, occurred less frequently with Thymoglobulin (17%) versus Atgam (36%) (P=O.011). A similar incidence of adverse events, post-therapy infections, and 1-year patient and graft survival rates were observed with both treatments. Conclusions. Thymoglobulin was found to be superior to Atgam in reversing acute rejection and preventing recurrent rejection after therapy in renal transplant recipients.

AB - Background. Thymoglobulin, a rabbit anti-human thymocyte globulin, was compared with Atgam, a horse anti-human thymocyte globulin for the treatment of acute rejection after renal transplantation. Methods. A multicenter, double-blind, randomized trial with enrollment stratification based on standardized histology (Banff grading) was conducted. Subjects received 7-14 days of Thymoglobulin (1.5 mg/kg/day) or Atgam (15 mg/kg/day). The primary end point was rejection reversal (return of serum creatinine level to or below the day 0 baseline value). Results. A total of 163 patients were enrolled at 25 transplant centers in the United States. No differences in demographics or transplant characteristics were noted. Intent-to-treat analysis demonstrated that Thymoglobulin 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 percentage of baseline (Thymoglobulin 72% and At-gam 80%; P=0.43), and improvement in posttreatment biopsy results (Thymoglobulin 65% and Atgam 50%; P=0.15) were not statistically different. T-cell depletion was maintained more effectively with Thymoglobulin than Atgam both at the end of therapy (P=0.001) and at day 30 (P=0.016). Recurrent rejection, at 90 days after therapy, occurred less frequently with Thymoglobulin (17%) versus Atgam (36%) (P=O.011). A similar incidence of adverse events, post-therapy infections, and 1-year patient and graft survival rates were observed with both treatments. Conclusions. Thymoglobulin was found to be superior to Atgam in reversing acute rejection and preventing recurrent rejection after therapy in renal transplant recipients.

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