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

December 11, 2018 updated by: J.S.F. Sanders, University Medical Center Groningen

Prevention of Relapses in PR3-ANCA-associated Vasculitis, a Tailored Approach

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).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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

Enrollment (Actual)

131

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands, 1081HV
        • VU University Medical Centre
      • Groningen, Netherlands, 9700 RB
        • University Medical Centre Groningen
      • Groningen, Netherlands, 9700RM
        • Martini Hospital Groningen
      • Leeuwarden, Netherlands, 8901BR
        • Medical Centre Leeuwarden
      • Maastricht, Netherlands, 6229 HX
        • University Hospital Maastricht
      • Nijmegen, Netherlands, 6525GC
        • UMC St Radboud
      • Rotterdam, Netherlands, 3000CA
        • Erasmus Medical Centre
      • Utrecht, Netherlands, 3508GA
        • University Medical Centre Utrecht

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
disease free survival
Time Frame: four years after diagnosis
four years after diagnosis

Secondary Outcome Measures

Outcome Measure
Time Frame
cumulative organ damage
Time Frame: four years after diagnosis
four years after diagnosis
side-effects
Time Frame: up to four years after diagnosis
up to four years after diagnosis
cumulative dosages of cyclophosphamide, prednisolone and azathioprine
Time Frame: up to four years after diagnosis
up to four years after diagnosis
quality of life
Time Frame: four years after diagnosis
four years after diagnosis

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Groningen

Collaborators

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 and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2003

Primary Completion (Actual)

June 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

August 9, 2005

First Submitted That Met QC Criteria

August 9, 2005

First Posted (Estimate)

August 10, 2005

Study Record Updates

Last Update Posted (Actual)

December 13, 2018

Last Update Submitted That Met QC Criteria

December 11, 2018

Last Verified

December 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AZA-ANCA-1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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