Brief Summary

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

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.

• Study Type: Interventional
• Study Design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
• Study Primary Completion Date: April 2004

Detailed Clinical Trial 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 Used in this Clinical Trial

• Drug: mycophenolate mofetil
  • MMF,1.0g/d

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: mycophenolate mofetil

Outcome Measures for this Clinical Trial

Primary Measures

• The efficacy of MMF compared to CTX in inducing remission and improving renal function in subjects with ANCA associated vasculitis.
  • Time Frame: 24 months
    Safety Issue?: Yes

Criteria for Participation in this Clinical Trial

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

• Lead Sponsor
  • Nanjing University School of Medicine
• Provider of Information About this Clinical Study
  • Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing University School of Medicine
• Overall Official(s)
  • Lei-Shi Li, M.D., Study Chair, Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine