MMF Versus CTX in the Induction Treatment of ANCA Associated Vasculitis

Study Overview
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Brief Summary
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The purpose of this study is to access the efficacy of MMF compared to CTX in inducing remission and improving renal function in subjects with ANCA associated vasculitis with renal involvement.

Detailed Description
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The ANCA-associated vasculitides can be life threatening. Glucocorticoids and cyclophosphamide therapy is effective in about 80% patients. However, the side effects such as bone marrow suppression, infection, cystitis, infertility, myelodysplasia preclude further use of cyclophosphamide in some patients and the relapse rate is high. Recent studies have shown that mycophenolic acid(MPA), the active metabolite of mycophenolate mofetil(MMF), could exhibit multifarious effects on endothelial cells, including inhibition of ICAM-1 expression, neutrophil attachment,IL-6 secretion, and the process of angiogenesis, which contribute to the efficacy of MMF in the treatment of vasculitic lesions such as lupus nephritis with vasculitic lesions. This study was a feasibility study to assess the safety and effectiveness of MMF in inducing remission in subjects with ANCA-associated SVV compared with pulse intravenous cyclophosphamide. After enrollment, subjects were followed longitudinally, and formal measurements of disease activity were determined using the Birmingham Vasculitis Activity Score (BVAS).

Official Title
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Mycophenolate Mofetil Versus Cyclophosphamide in the Induction Treatment of ANCA Associated Vasculitis

Conditions
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Vasculitis, Anti-Neutrophil Cytoplasmic Antibody

Intervention / Treatment
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* Drug: mycophenolate mofetil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A new diagnosis of ANCA associated vasculitis (eg. MPA or Wegener granulomatous, or renal limited vasculitis) proved by histology and serology. Renal involvement attributable to active ANCA associated vasculitis with at least one of the following: Elevated serum creatinine between 150 and 500 umol/l - renal biopsy Demonstrating paucin -immune necrotizing glomerulonephritis Red cell casts Haematuria with > 30 red blood cells/HPF and proteinuria > 1g/24h Serum ANCA positive by indirect immunofluorescence (IIF) and positivity in the anti-PR3 or anti-MPO by ELISA Age 18 65 years Exclusion Criteria: More than two weeks treatment with cyclophosphamide (CYC) or other cytotoxic drug within previous 6 months or with oral corticosteroids (OCS) for more than 4 weeks Co-existence of another multisystem autoimmune disease, e.g. SLE Serum creatinine > 500umol/l Severe viral infection(HBV, HCV, CMV) within 3 months of first randomization or known HIV infection Congenial or acquired immunodeficiency Immediately life-threatening organ manifestations (e.g. lung haemorrhage or dialysis dependence) Previous malignancy Pregnancy or inadequate contraception if female Anti-GBM antibody positivity Cerebral infarction due to vasculitis Rapidly progressive optic neuropathy or retinal vasculitis or orbital pseudotumour Massive gastro-intestinal bleeding Heart failure due to pericarditis or myocarditis Liver dysfunction measured on at least 2 separate occasions Age < 18y or Age > 65y

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

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> | Drug: mycophenolate mofetil<br>* MMF,1.0g/d<br>* Other names: MMF,cellcept,mycophenolate mofetil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The efficacy of MMF compared to CTX in inducing remission and improving renal function in subjects with ANCA associated vasculitis. |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ANCA, vasculitis, mycophenolate mofetil, cyclophosphamide, treatment