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

Sponsor

University Medical Center Groningen (Other)

Overall Status

Terminated

CT.gov ID

NCT00128895

Collaborator

ZonMw: The Netherlands Organisation for Health Research and Development (Other), Dutch Arthritis Association (Industry), Dutch Kidney Foundation (Other)

131

Enrollment

Locations

Arms

138

Duration (Months)

16.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Vasculitis	Drug: azathioprine	Phase 4

Detailed Description

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

131 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2003

Actual Primary Completion Date :

Jun 1, 2014

Actual Study Completion Date :

Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: azathioprine, standard standard azathioprine maintenance upto one year after diagnosis, subsequently tapering of azathioprine with 25 mg per 3 months	Drug: azathioprine azathioprine 2 mg/kg oral once daily, duration according to arm
Experimental: azathioprine, longterm longterm maintenance with azathioprine upto four years after diagnosis, subsequently azathioprine will be tapered with 25 mg per 3 months	Drug: azathioprine azathioprine 2 mg/kg oral once daily, duration according to arm

Arm

Intervention/Treatment

Active Comparator: azathioprine, standard

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

Drug: azathioprine

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

Experimental: azathioprine, longterm

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

Drug: azathioprine

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

Outcome Measures

Primary Outcome Measures

disease free survival [four years after diagnosis]

Secondary Outcome Measures

cumulative organ damage [four years after diagnosis]
side-effects [up to four years after diagnosis]
cumulative dosages of cyclophosphamide, prednisolone and azathioprine [up to four years after diagnosis]
quality of life [four years after diagnosis]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	VU University Medical Centre	Amsterdam	Netherlands	1081HV
2	University Medical Centre Groningen	Groningen	Netherlands	9700 RB
3	Martini Hospital Groningen	Groningen	Netherlands	9700RM
4	Medical Centre Leeuwarden	Leeuwarden	Netherlands	8901BR
5	University Hospital Maastricht	Maastricht	Netherlands	6229 HX
6	UMC St Radboud	Nijmegen	Netherlands	6525GC
7	Erasmus Medical Centre	Rotterdam	Netherlands	3000CA
8	University Medical Centre Utrecht	Utrecht	Netherlands	3508GA