The Mycophenolate Steroid Sparing (MYSS) study demonstrated that, in the setting of a
maintenance immunosuppressive regimen without steroids, mycophenolate mofetil (MMF) and
azathioprine (AZA) provided the same efficacy in preventing acute rejection episodes and
allograft dysfunction in kidney transplant recipients. Induction therapy with basiliximab
combined with low-dose thymoglobulin (RATG), through a transient depletion/inhibition of T
lymphocytes, allows further reducing the need for maintenance immunosuppression.
Aim of the present study is to assess whether under this induction strategy MMF and AZA are
equally effective in preventing acute rejection and chronic allograft nephropathy (CAN), even
after cyclosporine (CsA) withdrawal.
Two-hundred-twenty-four kidney transplant recipients from deceased donors given induction
therapy with two 20 mg basiliximab injections 4 days apart and a seven-day course of RATG
(0.5 mg/kg/day), will be randomly allocated on a 1:1 basis to 3-year treatment with low-dose
MMF or AZA, added-on CsA maintenance therapy. At 1 year, rejection-free patients with no
evidence of tubulitis at kidney biopsy will withdraw CsA and will have a kidney biopsy 3 year
post-transplant for evaluating the presence and severity of CAN. Should the cumulative
incidence of acute rejection exceed 15% during CsA withdrawal the study will be stopped.
Should the incidence differ by >30% between the two treatment arms, all patients will be
given the most effective treatment and the follow up will be continued. A final biopsy will
be repeated 4 years post-transplant.
Most patients are expected to be effectively maintained on single drug immunosuppression,
which implies less steroid- and CsA- related complications and treatment costs. MMF is
expected to prevent CAN more effectively than AZA. However, should AZA be more or as
effective compared to MMF, at study end all patients could be shifted to AZA, that is 15-fold
less expensive than MMF. Extended to clinical practice, these findings should translate in
improved patient care and major cost-savings for the Health Care System.
Phase:
Phase 4
Details
Lead Sponsor:
Mario Negri Institute for Pharmacological Research