Clinical trial NCT00128895: Prevention of Relapses in Proteinase 3 (PR3)-Anti-neutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis
Official title: Prevention of Relapses in PR3-ANCA-associated Vasculitis, a Tailored Approach
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Vasculitis
Keywords: Wegener's granulomatosis, ANCA, vasculitis, proteinase 3
ANCA-associated vasculitis
ANCA
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
name: Dutch Arthritis Association
name: Dutch Kidney Foundation
First posted: 2005-08-10
Enrollment: 131
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: 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).

Eligibility criteria: Inclusion Criteria:

* Newly diagnosed ANCA-associated vasculitis
* PR3-ANCA antibodies present
* Indication for treatment with cyclophosphamide and prednisolone

Exclusion Criteria:

* Intolerance or allergy to azathioprine

Primary outcomes:
measure: disease free survival
timeFrame: four years after diagnosis
Secondary outcomes:
measure: cumulative organ damage
timeFrame: four years after diagnosis
measure: side-effects
timeFrame: up to four years after diagnosis
measure: cumulative dosages of cyclophosphamide, prednisolone and azathioprine
timeFrame: up to four years after diagnosis
measure: quality of life
timeFrame: four years after diagnosis
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: VU University Medical Centre
city: Groningen
country: Netherlands
facility: University Medical Centre Groningen
city: Groningen
country: Netherlands
facility: Martini Hospital Groningen
city: Leeuwarden
country: Netherlands
facility: Medical Centre Leeuwarden
city: Maastricht
country: Netherlands
facility: University Hospital Maastricht
city: Nijmegen
country: Netherlands
facility: UMC St Radboud
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Centre
city: Utrecht
country: Netherlands
facility: University Medical Centre Utrecht
Study officials:
affiliation: University Medical Center Groningen
name: Coen A Stegeman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sanders JS, de Joode AA, DeSevaux RG, Broekroelofs J, Voskuyl AE, van Paassen P, Kallenberg CG, Tervaert JW, Stegeman CA. Extended versus standard azathioprine maintenance therapy in newly diagnosed proteinase-3 anti-neutrophil cytoplasmic antibody-associated vasculitis patients who remain cytoplasmic anti-neutrophil cytoplasmic antibody-positive after induction of remission: a randomized clinical trial. Nephrol Dial Transplant. 2016 Sep;31(9):1453-9. doi: 10.1093/ndt/gfw211. Epub 2016 May 30.