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

NCT ID: NCT00128895

Last Updated: 2018-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

131 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-06-30

Study Completion Date

2014-12-31

Brief Summary

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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

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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).

Conditions

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Vasculitis

Keywords

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Wegener's granulomatosis, ANCA, vasculitis, proteinase 3 ANCA-associated vasculitis ANCA

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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azathioprine, standard

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

Group Type ACTIVE_COMPARATOR

azathioprine

Intervention Type DRUG

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

azathioprine, longterm

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

Group Type EXPERIMENTAL

azathioprine

Intervention Type DRUG

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

Interventions

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azathioprine

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role collaborator

Dutch Arthritis Association

INDUSTRY

Sponsor Role collaborator

Dutch Kidney Foundation

OTHER

Sponsor Role collaborator

University Medical Center Groningen

OTHER

Sponsor Role lead

Responsible Party

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J.S.F. Sanders

dr JSF Sanders

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Coen A Stegeman, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Locations

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VU University Medical Centre

Amsterdam, , Netherlands

Site Status

University Medical Centre Groningen

Groningen, , Netherlands

Site Status

Martini Hospital Groningen

Groningen, , Netherlands

Site Status

Medical Centre Leeuwarden

Leeuwarden, , Netherlands

Site Status

University Hospital Maastricht

Maastricht, , Netherlands

Site Status

UMC St Radboud

Nijmegen, , Netherlands

Site Status

Erasmus Medical Centre

Rotterdam, , Netherlands

Site Status

University Medical Centre Utrecht

Utrecht, , Netherlands

Site Status

Countries

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Netherlands

References

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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.

Reference Type RESULT
PMID: 27242368 (View on PubMed)

Other Identifiers

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AZA-ANCA-1

Identifier Type: -

Identifier Source: org_study_id