Mycophenolate Mofetil for Treatment of Relapses of Wegener's Disease or Microscopic Polyangiitis (MPA)

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy and safety of a new drug, mycophenolate mofetil, for the treatment of relapses of ANCA-associated vasculitis (Wegener's granulomatosis or microscopic polyangiitis). Therefore, we compare the standard therapy with cyclophosphamide to mycophenolate mofetil. The investigators expect mycophenolate mofetil to be less toxic and almost equally effective as cyclophosphamide.

Detailed Description
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Treatment of ANCA-associated vasculitis consists of two phases: remission induction with highly effective, but also relatively toxic drugs, and, secondly, after remission is achieved, maintenance therapy with less toxic drugs. The standard induction therapy of a relapse of Wegener's granulomatosis or microscopic polyangiitis consists of the combination of cyclophosphamide and prednisolone. Although this induction therapy is very effective, it is very toxic as well. Searching for an alternative for cyclophosphamide, we will test the efficacy and safety of a new combination therapy with mycophenolate mofetil and prednisolone. We will compare the effect and safety of the standard induction therapy with the new therapy. When relapses occur, patients will be randomized for either the standard therapy with cyclophosphamide or for mycophenolate mofetil.

Official Title
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Comparative Study of the Efficacy of Induction Therapy With Cyclophosphamide or Mycophenolate Mofetil for Non-Life-Threatening Relapses of PR3- or MPO-ANCA Associated Vasculitis

Conditions
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Wegener's Granulomatosis, 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: First or second relapse ANCA-associated vasculitis PR3- or MPO-ANCA antibodies present or histological proof of relapse Adult Exclusion Criteria: Severe alveolar bleeding or (imminent) respiratory failure Renal failure (serum creatinine >500 umol/L or dialysis) Maintenance therapy before start of study consisting of: cyclophosphamide > 100 mg/day or prednisolone >25 mg/day Intolerance or allergy for cyclophosphamide, mycophenolate mofetil or azathioprine Gravidity or inadequate anticonception

Ages Eligible for Study
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Minimum Age: 18 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: 1<br>mycophenolate and steroids as remission induction, followed by azathioprine maintenance therapy | Drug: mycophenolate mofetil<br>* 2000 mg mycophenolate per day combined with steroids for induction remission, followed by azathioprine standard maintenance therapy<br>|
| Active Comparator: 2<br>cyclophosphamide | Drug: cyclophosphamide<br>* 2 mg/kg/d, combined with steroids, for remission induction, followed by standard azathioprine maintenance therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| remission induction rate |  | 6 months | 
| disease free survival after 2 and 4 years |  | 2 and 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to remission |  | 9 months | 
| cumulative organ damage |  | 4 years | 
| side-effects |  | 4 years | 
| ANCA titres over time |  | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Induction therapy, ANCA-associated vasculitis, Wegener's granulomatosis, microscopic polyangiitis, mycophenolate mofetil, cyclophosphamide