Clinical trial NCT00103792: Mycophenolate Mofetil for Treatment of Relapses of Wegener's Disease or Microscopic Polyangiitis (MPA)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Wegener's Granulomatosis
Vasculitis
Keywords: Induction therapy
ANCA-associated vasculitis
Wegener's granulomatosis
microscopic polyangiitis
mycophenolate mofetil
cyclophosphamide
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2005-02-15
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: remission induction rate
timeFrame: 6 months
measure: disease free survival after 2 and 4 years
timeFrame: 2 and 4 years
Secondary outcomes:
measure: time to remission
timeFrame: 9 months
measure: cumulative organ damage
timeFrame: 4 years
measure: side-effects
timeFrame: 4 years
measure: ANCA titres over time
timeFrame: 4 years
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Centre Groningen
Study officials:
affiliation: UMCG Groningen
name: Coen Stegeman, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stegeman CA; Cohen Tervaert JW. Mycophenolate mofetil for remission induction in patients with active Wegener's Granulomatosis (WG) intolerant for cyclophosphamide. J Am Soc Nephrol(11):98A, 2000