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

NCT00128895 | Terminated Phase 4

• 1 other identifier: AZA-ANCA-1
• Study Type: interventional
• Target: 131
• Locations: 1 country
• Sites: 8

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).

Conditions

Vasculitis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• disease free survival

  four years after diagnosis

Secondary Outcomes (4)

• 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

Study Arms (2)

azathioprine, standard

ACTIVE COMPARATOR

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

Drug: azathioprine

azathioprine, longterm

EXPERIMENTAL

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

Drug: azathioprine

Interventions

azathioprine DRUG

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

azathioprine, longterm; azathioprine, standard

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Intolerance or allergy to azathioprine

Sponsors & Collaborators

• University Medical Center Groningen: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator
• Dutch Arthritis Association: collaborator
• Dutch Kidney Foundation: collaborator

Study Sites (8)

VU University Medical Centre

Amsterdam, 1081HV, Netherlands

Location

University Medical Centre Groningen

Groningen, 9700 RB, Netherlands

Location

Martini Hospital Groningen

Groningen, 9700RM, Netherlands

Location

Medical Centre Leeuwarden

Leeuwarden, 8901BR, Netherlands

Location

University Hospital Maastricht

Maastricht, 6229 HX, Netherlands

Location

UMC St Radboud

Nijmegen, 6525GC, Netherlands

Location

Erasmus Medical Centre

Rotterdam, 3000CA, Netherlands

Location

University Medical Centre Utrecht

Utrecht, 3508GA, Netherlands

Location

Related 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-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.

  PMID: 27242368 RESULT

MeSH Terms

Conditions

Vasculitis; Granulomatosis with Polyangiitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Interventions

Azathioprine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Systemic Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Coen A Stegeman, MD, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: dr JSF Sanders

Study Record Dates

• First Submitted: August 9, 2005
• First Posted: August 10, 2005
• Study Start: June 1, 2003
• Primary Completion: June 1, 2014
• Study Completion: December 1, 2014
• Last Updated: December 13, 2018

Record last verified: 2018-12

Locations

NL (8)