Anti-Neutrophil Cytoplasmic Antibody, Vasculitis
Conditions
Keywords
ANCA, vasculitis, mycophenolate mofetil, cyclophosphamide, treatment
Brief summary
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
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).
Interventions
DRUGmycophenolate mofetil
MMF,1.0g/d
Sponsors
Nanjing University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. A new diagnosis of ANCA associated vasculitis (eg. MPA or Wegener granulomatous, or renal limited vasculitis) proved by histology and serology. 2. 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 3. Serum ANCA positive by indirect immunofluorescence (IIF) and positivity in the anti-PR3 or anti-MPO by ELISA 4. Age 18\ 65 years
Exclusion criteria
1. 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 2. Co-existence of another multisystem autoimmune disease, e.g. SLE 3. Serum creatinine \> 500umol/l 4. Severe viral infection(HBV, HCV, CMV) within 3 months of first randomization or known HIV infection 5. Congenial or acquired immunodeficiency 6. Immediately life-threatening organ manifestations (e.g. lung haemorrhage or dialysis dependence) 7. Previous malignancy 8. Pregnancy or inadequate contraception if female 9. Anti-GBM antibody positivity 10. Cerebral infarction due to vasculitis 11. Rapidly progressive optic neuropathy or retinal vasculitis or orbital pseudotumour 12. Massive gastro-intestinal bleeding 13. Heart failure due to pericarditis or myocarditis 14. Liver dysfunction measured on at least 2 separate occasions 15. Age \< 18y or Age \> 65y
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The efficacy of MMF compared to CTX in inducing remission and improving renal function in subjects with ANCA associated vasculitis. | 24 months |
Countries
China
Outcome results
None listed