Prevention of Relapses in Proteinase 3 (PR3)-Anti-neutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis
- Registration Number
- NCT00128895
- Lead Sponsor
- University Medical Center Groningen
- Brief Summary
Treatment of patients with PR3-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. Currently, remission-maintenance therapy with azathioprine is stopped after approximately 18 months. However, the optimal duration of azathioprine maintenance therapy is unknown.
The investigators have found that patients with PR3-ANCA-associated vasculitis who remain cytoplasmic anti-neutrophil cytoplasmic autoantibody (C-ANCA) positive after induction of remission have an increased risk to experience relapse of disease. Therefore they will test whether relapse risk in these patients can be reduced by extending maintenance therapy at the cost of acceptable therapy related toxicity. After induction of stable remission, ANCA will be measured by immunofluorescence (IIF). C-ANCA positive patients will be randomized for either standard therapy with azathioprine (until 18 months after diagnosis), or longterm azathioprine maintenance therapy (until 48 months after diagnosis).
- Detailed Description
Treatment of patients with PR3-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. Currently, remission-maintenance therapy with azathioprine is stopped after approximately 18 months. However, the optimal duration of azathioprine maintenance therapy is unknown.
The investigators have found that patients with PR3-ANCA-associated vasculitis who remain C-ANCA positive after induction of remission have an increased risk to experience relapse of disease (MC Slot et al. Arthritis Rheum. 2004 15;51(2):269-73). Therefore they will test whether relapse risk in these patients can be reduced by extending maintenance therapy at the cost of acceptable therapy related toxicity. After induction of stable remission, ANCA will be measured by IIF. C-ANCA positive patients will be randomized for either standard therapy with azathioprine (until 18 months after diagnosis), or longterm azathioprine maintenance therapy (until 48 months after diagnosis).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 131
- Newly diagnosed ANCA-associated vasculitis
- PR3-ANCA antibodies present
- Indication for treatment with cyclophosphamide and prednisolone
- Intolerance or allergy to azathioprine
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description azathioprine, longterm azathioprine longterm maintenance with azathioprine upto four years after diagnosis, subsequently azathioprine will be tapered with 25 mg per 3 months azathioprine, standard azathioprine standard azathioprine maintenance upto one year after diagnosis, subsequently tapering of azathioprine with 25 mg per 3 months
- Primary Outcome Measures
Name Time Method disease free survival four years after diagnosis
- Secondary Outcome Measures
Name Time Method cumulative organ damage four years after diagnosis side-effects up to four years after diagnosis quality of life four years after diagnosis cumulative dosages of cyclophosphamide, prednisolone and azathioprine up to four years after diagnosis
Trial Locations
- Locations (8)
Erasmus Medical Centre
🇳🇱Rotterdam, Netherlands
VU University Medical Centre
🇳🇱Amsterdam, Netherlands
University Hospital Maastricht
🇳🇱Maastricht, Netherlands
University Medical Centre Groningen
🇳🇱Groningen, Netherlands
Martini Hospital Groningen
🇳🇱Groningen, Netherlands
UMC St Radboud
🇳🇱Nijmegen, Netherlands
Medical Centre Leeuwarden
🇳🇱Leeuwarden, Netherlands
University Medical Centre Utrecht
🇳🇱Utrecht, Netherlands