Clinical Trial of Mycophenolate Versus Cyclophosphamide in ANCA Vasculitis
Clinical Trial of Mycophenolate Versus Cyclophosphamide in ANCA Vasculitis
The purpose of this study is to investigate whether mycophenolate mofetil is effective as
 treatment for new cases of ANCA associated vasculitis.
There is a clear need for improved therapy in ANCA associated vasculitis where current
 treatments are toxic and contribute to poor outcomes. Conventional therapy combines
 cyclophosphamide with prednisolone but is associated with severe adverse events in 35%, early
 mortality, malignancy and infertility. Mycophenolate mofetil (MMF) is a newer
 immunosuppressive drug which has superior efficacy to azathioprine in solid organ
 transplantation. MMF is an effective alternative to cyclophosphamide in lupus nephritis. Open
 label studies and retrospective surveys point to the efficacy and low toxicity of MMF in
 vasculitis.

 We hypothesise that MMF not be less effective than cyclophosphamide for remission induction
 in AASV. 140 new patients will be randomised to MMF 3g/day or a European consensus
 intravenous cyclophosphamide regimen, with the same prednisolone dosing. Following a six
 month induction course all patients will receive consensus remission maintenance treatment
 with azathioprine and prednisolone. The primary end-point will be remission rate by six
 months, secondary end-points include relapse rate at 18 months and safety. The trial will be
 conducted in 10 countries by members of the European Vasculitis Study Group (EUVAS). The
 trial duration will be 42 months (24 months recruitment, 18 months follow up).
Inclusion Criteria:

 Inclusion (requires all):

 -  New diagnosis of AASV (WG or MPA) (within the previous six months)

 -  Active disease (defined by at least one major or three minor BVAS 2003 items, see
 appendix 1)

 -  ANCA positivity (c-ANCA and PR3-ANCA or p-ANCA and MPO-ANCA) or histology confirming
 active vasculitis from any organ (see appendix )

 -  Written informed consent

 Exclusion Criteria:

 -  Previous treatment with:

 -  MMF: more than two weeks ever.

 -  Cyclophosphamide: more than two weeks daily oral or more than 1 pulse of IV CYC
 (15mg/kg)

 -  Rituximab or high dose intravenous immunoglobulin within the last twelve months

 -  Active infection (including hepatitis B, C, HIV and tuberculosis).

 -  Known hypersensitivity to MMF, AZA or CYC.

 -  Cancer or an individual history of cancer (other than resected basal cell skin
 carcinoma).

 -  Females who are pregnant, breast feeding, or at risk of pregnancy and not using a
 medically acceptable form of contraception.

 -  Any condition judged by the investigator that would cause the study to be detrimental
 to the patient.

 -  Any other multi-system autoimmune disease including Churg Strauss angiitis, SLE, anti
 GBM disease and cryoglobulinaemia.