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MMF vs. AZA for Kidney Transplantation (ATHENA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00494741
Recruitment Status : Completed
First Posted : July 2, 2007
Last Update Posted : December 13, 2017
Agenzia Italiana del Farmaco
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research

Brief 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.

Condition or disease Intervention/treatment Phase
Kidney Transplant Drug: mycophenolate mofetil Drug: azathioprine Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 233 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : May 2007
Actual Primary Completion Date : July 2016
Actual Study Completion Date : November 29, 2017

Arm Intervention/treatment
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.

Experimental: azathioprine Drug: azathioprine
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.

Primary Outcome Measures :
  1. 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. ]

Secondary Outcome Measures :
  1. - 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 ]

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00494741

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Hospital "Azienda Ospedaliera Ospedali Riuniti di Bergamo" Unit of Neprology and Dialysis
Bergamo, Italy
Hospital "Spedali Civili" - Unit of Nephrology and Dialysis
Brescia, Italy
Hospital "Niguarda Cà Granda"
Milano, Italy
Hospital "Azienda Ospedaliera di Padova" -
Padova, Italy
Policlinico Gemelli
Roma, Italy
Hospital "Az. Ospedaliero-Univeristaria S. Maria della Misericordia
Udine, Italy
Sponsors and Collaborators
Mario Negri Institute for Pharmacological Research
Agenzia Italiana del Farmaco
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Study Director: Norberto Perico, MD Mario Negri Institute for Pharmacological Research
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Mario Negri Institute for Pharmacological Research Identifier: NCT00494741    
Other Study ID Numbers: ATHENA
2006-005604-14 ( EudraCT Number )
First Posted: July 2, 2007    Key Record Dates
Last Update Posted: December 13, 2017
Last Verified: December 2017
Additional relevant MeSH terms:
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Mycophenolic Acid
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents