MMF vs. AZA for Kidney Transplantation (ATHENA)
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Kidney Transplant |
Drug: mycophenolate mofetil Drug: azathioprine |
Phase 4 |
| Study Type: | Interventional |
| 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 ]
| Estimated Enrollment: | 224 |
| Study Start Date: | May 2007 |
| Estimated Study Completion Date: | September 2016 |
| Estimated Primary Completion Date: | May 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| 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.
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years to 75 Years |
| Genders Eligible for Study: | Both |
| 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.
Contacts and Locations| Italy | |
| 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 | |
| Study Director: | Norberto Perico, MD | Mario Negri Institute for Pharmacological Research |
More Information
No publications provided by Mario Negri Institute for Pharmacological Research
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Mario Negri Institute for Pharmacological Research |
| ClinicalTrials.gov Identifier: | NCT00494741 History of Changes |
| Other Study ID Numbers: | ATHENA, 2006-005604-14 |
| Study First Received: | June 29, 2007 |
| Last Updated: | February 22, 2013 |
| Health Authority: | Italy: Ministry of Health |
Additional relevant MeSH terms:
|
Azathioprine Mycophenolate mofetil Mycophenolic Acid Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antimetabolites, Antineoplastic Antineoplastic Agents |
Therapeutic Uses Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antibiotics, Antineoplastic Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 23, 2013