The US multicenter double-blind, randomized, phase III trial of thymoglobulin versus atgam in the treatment of acute graft rejection episodes following renal transplantation: rationale for study design.

Overview

In this study intended to establish equivalence between two antibody therapies for acute rejection in kidney transplant recipients, it was important to develop a rigorous protocol. Assurance of the presence of acute rejection was imperative. Therefore, due to the lack of literature support for clinical assessment of renal dysfunction, histologic diagnosis of acute rejection was required for enrollment in the study. Likewise, supportive literature for a correlation between response to anti-rejection therapy and the severity of rejection lead to the decision that the study should be stratified by a measurement of rejection severity for which Banff criteria were used. Finally, quantification of the response to therapy was also measured against the available literature and a large, newly developed international database of kidney transplant rejection episodes (the Efficacy Endpoints database) where serum creatinine, expressed as a percentage of the baseline level at the time of rejection was shown to be the most effective, available clinical marker of rejection response. Therefore, the US Multicenter Phase III Trial for comparing Thymoglobulin to Atgam in the treatment of acute rejection exhibits a unique and detailed study design that could be implemented in future trials as well as in clinical practice to improve assessment of outcomes.