Prevention of Relapses in Proteinase 3 (PR3)-Anti-neutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis

University Medical Center Groningen (UMCG)

Status and phase: Terminated; Phase 4

Conditions: Vasculitis

Treatments: Drug: azathioprine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00128895

AZA-ANCA-1

Details and patient eligibility

About

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).

Full 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).

Enrollment: 131 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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131 participants in 2 patient groups

azathioprine, standard

Active Comparator group

Description:

standard azathioprine maintenance upto one year after diagnosis, subsequently tapering of azathioprine with 25 mg per 3 months

Treatment:

Drug: azathioprine

azathioprine, longterm

Experimental group

Description:

longterm maintenance with azathioprine upto four years after diagnosis, subsequently azathioprine will be tapered with 25 mg per 3 months

Treatment:

Drug: azathioprine