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

Vasculitis Clinical Trial

Official title:

Prevention of Relapses in PR3-ANCA-associated Vasculitis, a Tailored Approach

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00128895
• Other study ID #: AZA-ANCA-1
• Status: Terminated
• Phase: Phase 4
• Start date: June 2003
• Est. completion date: December 2014

Study information

• Verified date: December 2018
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Terminated
• Enrollment: 131
• Est. completion date: December 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
• Vasculitis

Intervention

Drug:
• azathioprine
azathioprine 2 mg/kg oral once daily, duration according to arm

Locations

Country	Name	City	State
Netherlands	VU University Medical Centre	Amsterdam
Netherlands	Martini Hospital Groningen	Groningen
Netherlands	University Medical Centre Groningen	Groningen
Netherlands	Medical Centre Leeuwarden	Leeuwarden
Netherlands	University Hospital Maastricht	Maastricht
Netherlands	UMC St Radboud	Nijmegen
Netherlands	Erasmus Medical Centre	Rotterdam
Netherlands	University Medical Centre Utrecht	Utrecht

Sponsors (4)

Lead Sponsor	Collaborator
University Medical Center Groningen	Dutch Arthritis Association, Dutch Kidney Foundation, ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

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-associ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	disease free survival		four years after diagnosis
Secondary	cumulative organ damage		four years after diagnosis
Secondary	side-effects		up to four years after diagnosis
Secondary	cumulative dosages of cyclophosphamide, prednisolone and azathioprine		up to four years after diagnosis
Secondary	quality of life		four years after diagnosis