Clinical Trial of Mycophenolate Versus Cyclophosphamide in ANCA Vasculitis

Study Overview
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Brief Summary
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The purpose of this study is to investigate whether mycophenolate mofetil is effective as treatment for new cases of ANCA associated vasculitis.

Detailed Description
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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).

Official Title
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A Randomised Clinical Trial of Mycophenolate Mofetil Versus Cyclophosphamide for Remission Induction in ANCA Associated Vasculitis.

Conditions
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Vasculitis

Intervention / Treatment
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* Drug: mycophenolate mofetil
* Drug: cyclophosphamide


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mycophenolate mofetil<br>Mycophenolate mofetil for 3-6 months until in stable remission, dose 2-3g/day | Drug: mycophenolate mofetil<br>* 2-3g/day for 3-6 months, in tablet, capsule or liquid form<br>* Other names: Cellcept;|
| Active Comparator: cyclophosphamide<br>pulsed intravenous cyclophosphamide 15mg/kg for 3-6 months (6-10 doses)until in stable remission | Drug: cyclophosphamide<br>* intravenous cyclophosphamide, 15mg/kg with dose reductions according to age and renal function, for 3-6 months (6-10 doses total)<br>* Other names: cytoxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission rates at 6 months | Assessed by BVAS score of zero on 2 consecutive assessments | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vasculitis, ANCA, mycophenolate mofetil, cyclophosphamide, Anti neutrophil cytoplasm antibody associated vasculitis