Tacrolimus/Everolimus Versus Tacrolimus/Enteric-Coated Mycophenolate Sodium
Status:
Completed
Trial end date:
2014-12-01
Target enrollment:
Participant gender:
Summary
A recent therapeutic strategy following renal transplantation includes simultaneous use of
reduced calcineurin inhibitor (CNI) dosing and maximized use of a non-nephrotoxic,
antiproliferative drug (inosine monophosphate dehydrogenase (IMPDH) or TOR inhibitor), with
the goals of reducing/avoiding CNI nephrotoxicity, the incidence of acute rejection, and
chronic allograft injury (CAI) (i.e., interstitial fibrosis/tubular atrophy), leading to more
favorable longer-term patient and graft survival.1-7 Early corticosteroid withdrawal has also
been used in the attempt to avoid well-known side effects while maintaining favorable patient
and graft survival.8-10 While the investigators center and numerous other centers have also
included single agent, antibody induction utilizing the lymphodepleting polyclonal antibody
rabbit anti-human thymocyte globulin (ATG), nondepleting human anti-interleukin-2 receptor
(CD25) monoclonal antibody daclizumab (Dac) or basiliximab, or lymphodepleting humanized
anti-CD52 monoclonal antibody alemtuzumab,11-17 evidence now suggests that an even more
effective induction strategy may include the combined use of more than one induction agent
(each with fewer doses than if used alone), with the goal of bringing the kidney transplant
recipient even closer (through more effectively timed lymphodepletion) to an optimally
immunosuppressed state, allowing further reduction in long-term maintenance drug dosing.18-25
The investigators have now successfully used dual ATG/Dac induction therapy in both
kidney-alone23-24 and simultaneous kidney-pancreas (SPK) transplantation,18-20 and a recent
report from the investigators center of kidney-alone and SPK recipients shows that the
addition of anti-CD25 to ATG for induction therapy more effectively delays the return of
peripheral blood CD25+ cells.25 In the kidney-alone recipient study 3 doses of ATG were
combined with 2 doses of Dac for induction,23-24 vs. the investigators previous studies
utilizing single agent induction with 7 doses of ATG or 5 doses of Dac.4,16,17 Successful
combination of ATG/basiliximab as dual induction in kidney transplantation has also been
reported elsewhere,21-22 along with equivalency in clinical outcomes using daclizumab vs.
basiliximab.13