MMF vs. AZA for Kidney Transplantation (ATHENA)
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.
Drug: mycophenolate mofetil
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized, Prospective, Multicenter Trial to Compare the Effect on Chronic Allograft Nephropathy Prevention of Mycophenolate Mofetil Versus Azathioprine as the Sole Immunosuppressive Therapy for Kidney Transplant Recipients|
- Cumulative incidence of biopsy-proven CAN at 3 years follow-up in patients completing CsA withdrawal in the two treatment groups (end phase B). [ Time Frame: At 3 years follow-up. ] [ Designated as safety issue: Yes ]
- - To assess the overall incidence of acute rejections at 1 and 2 years. - To assess the overall incidence of CAN at 3 years. - To assess graft and patient survival at 4 years. [ Time Frame: At 1,2,3 and 4 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||May 2007|
|Estimated Study Completion Date:||September 2016|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
|Experimental: mycophenolate mofetil||
Drug: mycophenolate mofetil
Patients randomized in this group will receive 750 mg of MMF per os twice a day starting on the day of transplant. MMF dose will be reduced in case of white blood cell count lower than 2,000/mm3 and whenever deemed clinically appropriate.
Patients randomized in this group will receive 75 mg of AZA per os (or 125 mg if body weight > 75 kg) once a day starting on the day of transplant. AZA dose will be reduced in case of white blood cell count lower than 2,000/mm3 and whenever deemed clinically appropriate.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00494741
|Hospital "Azienda Ospedaliera Ospedali Riuniti di Bergamo" Unit of Neprology and Dialysis|
|Hospital "Spedali Civili" - Unit of Nephrology and Dialysis|
|Hospital "Niguarda Cà Granda"|
|Hospital "Azienda Ospedaliera di Padova" -|
|Hospital "Az. Ospedaliero-Univeristaria S. Maria della Misericordia|
|Study Director:||Norberto Perico, MD||Mario Negri Institute for Pharmacological Research|