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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2011 by University Medical Centre Groningen.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
ZonMw: The Netherlands Organisation for Health Research and Development
Dutch Arthritis Association
Dutch Kidney Foundation
Information provided by (Responsible Party):
J.S.F. Sanders, University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT00128895
First received: August 9, 2005
Last updated: November 1, 2011
Last verified: November 2011
  Purpose

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 Intervention Phase
Vasculitis
Drug: azathioprine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prevention of Relapses in PR3-ANCA-associated Vasculitis, a Tailored Approach

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:
  • disease free survival [ Time Frame: four years after diagnosis ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • cumulative organ damage [ Time Frame: four years after diagnosis ] [ Designated as safety issue: No ]
  • side-effects [ Time Frame: up to four years after diagnosis ] [ Designated as safety issue: Yes ]
  • cumulative dosages of cyclophosphamide, prednisolone and azathioprine [ Time Frame: up to four years after diagnosis ] [ Designated as safety issue: No ]
  • quality of life [ Time Frame: four years after diagnosis ] [ Designated as safety issue: No ]

Estimated Enrollment: 180
Study Start Date: June 2003
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: azathioprine, standard
standard azathioprine maintenance upto one year after diagnosis, subsequently tapering of azathioprine with 35 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

Detailed 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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00128895

Contacts
Contact: Coen A Stegeman, MD, PhD +31503616161 c.a.stegeman@int.umcg.nl
Contact: Jan-Stephan F Sanders, MD +31503616161 j.sanders@int.umcg.nl

Locations
Netherlands
VU University Medical Centre Recruiting
Amsterdam, Netherlands, 1081HV
Contact: A Voskuyl, MD, PhD    31204444444    ae.voskuyl@vumc.nl   
University Medical Centre Groningen Recruiting
Groningen, Netherlands, 9700 RB
Contact: Coen A Stegeman, MD, PhD    +31503616161    c.a.stegeman@int.umcg.nl   
Principal Investigator: Coen A Stegeman, MD, PhD         
Sub-Investigator: Jan-Stephan F Sanders, MD         
Martini Hospital Groningen Recruiting
Groningen, Netherlands, 9700RM
Contact: W D Kloppenburg, MD, PhD    31505245245    w.d.kloppenburg@mzh.nl   
Medical Centre Leeuwarden Recruiting
Leeuwarden, Netherlands, 8901BR
Contact: J Broekroelofs, MD, PhD    31582866666    J.Broekroelofs@znb.nl   
University Hospital Maastricht Recruiting
Maastricht, Netherlands, 6229 HX
Contact: JW Cohen Tervaert, MD, PhD    +31-43-3876543    Jw.Cohentervaert@immuno.unimaas.nl   
Principal Investigator: JW Cohen Tervaert, MD, PhD         
UMC St Radboud Recruiting
Nijmegen, Netherlands, 6525GC
Contact: R de Sevaux, MD, PhD    310243611111    r.desevaux@nier.umcn.nl   
Erasmus Medical Centre Recruiting
Rotterdam, Netherlands, 3000CA
Contact: P Van Daele, MD, PhD    31104639222    p.l.a.vandaele@erasmusmc.nl   
University Medical Centre Utrecht Recruiting
Utrecht, Netherlands, 3508GA
Contact: R Hene, MD, PhD    31302509111      
Sponsors and Collaborators
University Medical Centre Groningen
ZonMw: The Netherlands Organisation for Health Research and Development
Dutch Arthritis Association
Dutch Kidney Foundation
Investigators
Principal Investigator: Coen A Stegeman, MD, PhD University Medical Centre Groningen
  More Information

No publications provided

Responsible Party: J.S.F. Sanders, dr JSF Sanders, University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT00128895     History of Changes
Other Study ID Numbers: AZA-ANCA-1
Study First Received: August 9, 2005
Last Updated: November 1, 2011
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by University Medical Centre Groningen:
Wegener's granulomatosis, ANCA, vasculitis, proteinase 3
ANCA-associated vasculitis
ANCA

Additional relevant MeSH terms:
Vasculitis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Vascular Diseases
Cardiovascular Diseases
Systemic Vasculitis
Autoimmune Diseases
Immune System Diseases
Azathioprine
Antibodies, Antineutrophil Cytoplasmic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 18, 2014