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

This study is ongoing, but not recruiting participants.
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: December 31, 2014
Last verified: December 2014
  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: December 2014
Primary Completion Date: June 2014 (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 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

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

Locations
Netherlands
VU University Medical Centre
Amsterdam, Netherlands, 1081HV
Martini Hospital Groningen
Groningen, Netherlands, 9700RM
University Medical Centre Groningen
Groningen, Netherlands, 9700 RB
Medical Centre Leeuwarden
Leeuwarden, Netherlands, 8901BR
University Hospital Maastricht
Maastricht, Netherlands, 6229 HX
UMC St Radboud
Nijmegen, Netherlands, 6525GC
Erasmus Medical Centre
Rotterdam, Netherlands, 3000CA
University Medical Centre Utrecht
Utrecht, Netherlands, 3508GA
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: December 31, 2014
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:
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Vasculitis
Autoimmune Diseases
Cardiovascular Diseases
Immune System Diseases
Systemic Vasculitis
Vascular Diseases
Antibodies, Antineutrophil Cytoplasmic
Azathioprine
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on May 26, 2015