MMF vs. AZA for Kidney Transplantation

NCT00494741 | Completed Phase 4

• 2 other identifiers: ATHENA2006-005604-14
• Study Type: interventional
• Target: 233
• Locations: 1 country
• Sites: 6

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.

Conditions

Kidney Transplant

Outcome Measures

Primary Outcomes (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).

  At 3 years follow-up.

Secondary Outcomes (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.

  At 1,2,3 and 4 years

Study Arms (2)

mycophenolate mofetil

EXPERIMENTAL

Drug: mycophenolate mofetil

azathioprine

EXPERIMENTAL

Drug: azathioprine

Interventions

mycophenolate mofetil DRUG

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.

mycophenolate mofetil

azathioprine DRUG

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.

azathioprine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females aged 18 years or more;
• First single or double kidney transplant from deceased donors;
• Written informed consent.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• Agenzia Italiana del Farmaco: collaborator

Study Sites (6)

Hospital "Azienda Ospedaliera Ospedali Riuniti di Bergamo" Unit of Neprology and Dialysis

Bergamo, Italy

Location

Hospital "Spedali Civili" - Unit of Nephrology and Dialysis

Brescia, Italy

Location

Hospital "Niguarda Cà Granda"

Milan, Italy

Location

Hospital "Azienda Ospedaliera di Padova" -

Padua, Italy

Location

Policlinico Gemelli

Roma, Italy

Location

Hospital "Az. Ospedaliero-Univeristaria S. Maria della Misericordia

Udine, Italy

Location

Related Publications (2)

• Ruggenenti P, Cravedi P, Gotti E, Plati A, Marasa M, Sandrini S, Bossini N, Citterio F, Minetti E, Montanaro D, Sabadini E, Tardanico R, Martinetti D, Gaspari F, Villa A, Perna A, Peraro F, Remuzzi G. Mycophenolate mofetil versus azathioprine in kidney transplant recipients on steroid-free, low-dose cyclosporine immunosuppression (ATHENA): A pragmatic randomized trial. PLoS Med. 2021 Jun 24;18(6):e1003668. doi: 10.1371/journal.pmed.1003668. eCollection 2021 Jun.

  PMID: 34166370 DERIVED

• Cravedi P, Mannon RB, Remuzzi G. Lymphocyte depletion for kidney transplantation: back to the past? Nat Clin Pract Nephrol. 2008 Oct;4(10):534-5. doi: 10.1038/ncpneph0914. Epub 2008 Aug 26. No abstract available.

  PMID: 18725917 DERIVED

MeSH Terms

Interventions

Mycophenolic Acid; Azathioprine

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Thionucleosides; Sulfur Compounds; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Norberto Perico, MD

  Mario Negri Institute for Pharmacological Research

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2007
• First Posted: July 2, 2007
• Study Start: May 1, 2007
• Primary Completion: July 1, 2016
• Study Completion: November 29, 2017
• Last Updated: December 13, 2017

Record last verified: 2017-12

Locations

IT (6)