MMF vs. AZA for Kidney Transplantation

• Status: Completed
• Trial end date: 2017-11-29
• Target enrollment: 0
• Participant gender: All

Summary

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
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mario Negri Institute for Pharmacological Research
• Collaborator: Agenzia Italiana del Farmaco
• Treatments: Azathioprine; Mycophenolate mofetil; Mycophenolic Acid

Criteria

Inclusion Criteria:

• Males and females aged 18 years or more;

• First single or double kidney transplant from deceased donors;

• Written informed consent.

Exclusion Criteria:

• Specific contraindications to RATG therapy such as severe leucopenia (WBC<2000/mm3);

• High immunological risk - such as second transplant recipients or those who have a panel reactivity > 10%;

• History of malignancy (except non metastatic basal or squamous cell carcinoma of the skin that has been treated successfully;

• Evidence of active hepatitis C virus, hepatitis B virus or human acquired immunodeficiency virus infection;

• Any chronic clinical conditions that may affect completion of the trial or confound data interpretation;

• Pregnancy or lactating;

• Women of childbearing potential without following a scientifically accepted form of contraception;

• Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequence of the trial;

• Evidence of an uncooperative attitude;

• Any evidence that patient will not be able to complete the trial follow-up.