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

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ClinicalTrials.gov Identifier: NCT00128895
Recruitment Status : Terminated
First Posted : August 10, 2005
Last Update Posted : December 13, 2018
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 Center Groningen

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:

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).


Study Type : Interventional  (Clinical Trial)
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 : June 2003
Actual Primary Completion Date : June 2014
Actual Study Completion Date : December 2014


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




Primary Outcome Measures :
  1. disease free survival [ Time Frame: four years after diagnosis ]

Secondary Outcome Measures :
  1. cumulative organ damage [ Time Frame: four years after diagnosis ]
  2. side-effects [ Time Frame: up to four years after diagnosis ]
  3. cumulative dosages of cyclophosphamide, prednisolone and azathioprine [ Time Frame: up to four years after diagnosis ]
  4. quality of life [ Time Frame: four years after diagnosis ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00128895


Locations
Netherlands
VU University Medical Centre
Amsterdam, Netherlands, 1081HV
University Medical Centre Groningen
Groningen, Netherlands, 9700 RB
Martini Hospital Groningen
Groningen, Netherlands, 9700RM
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 Center 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 Center Groningen

Publications of Results:
Responsible Party: J.S.F. Sanders, dr JSF Sanders, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT00128895     History of Changes
Other Study ID Numbers: AZA-ANCA-1
First Posted: August 10, 2005    Key Record Dates
Last Update Posted: December 13, 2018
Last Verified: December 2018

Keywords provided by J.S.F. Sanders, University Medical Center 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
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents