VasculitisPhase 4NCT00128895
Prevention of Relapses in Proteinase 3 (PR3)-Anti-neutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis
A Phase 4 study testing azathioprine in people with Vasculitis, run by University Medical Center Groningen at 8 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Vasculitis
- What is being tested?
- azathioprine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 131 participants
- Where
- 8 sitesNetherlands
- Study dates
- Jun 2003to Dec 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Newly diagnosed ANCA-associated vasculitis
- PR3-ANCA antibodies present
- Indication for treatment with cyclophosphamide and prednisolone
Who cannot join
- Intolerance or allergy to azathioprine
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Netherlands8 sites
VU University Medical Centre
Amsterdam, 1081HV
University Medical Centre Groningen
Groningen, 9700 RB
Martini Hospital Groningen
Groningen, 9700RM
Medical Centre Leeuwarden
Leeuwarden, 8901BR
University Hospital Maastricht
Maastricht, 6229 HX
UMC St Radboud
Nijmegen, 6525GC
Erasmus Medical Centre
Rotterdam, 3000CA
University Medical Centre Utrecht
Utrecht, 3508GA
About this study
Official title: 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).
Read the 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).
- Conditions
- Vasculitis
- Being tested
- azathioprine
- Keywords
- Wegener's granulomatosis, ANCA, vasculitis, proteinase 3, ANCA-associated vasculitis, ANCA
- Medical subject headings
- Vasculitis, Granulomatosis with Polyangiitis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
azathioprineDrug
azathioprine 2 mg/kg oral once daily, duration according to arm
| Study group | Role | What they receive |
|---|---|---|
| azathioprine, standard | Active comparator | standard azathioprine maintenance upto one year after diagnosis, subsequently tapering of azathioprine with 25 mg per 3 months Receives: 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 Receives: Drug: azathioprine |
What is being measured
The primary outcome is the main question the study is designed to answer.
disease free survival
Measured: four years after diagnosis
Secondary outcomes (4)
cumulative organ damage
Measured: four years after diagnosis
side-effects
Measured: up to four years after diagnosis
cumulative dosages of cyclophosphamide, prednisolone and azathioprine
Measured: up to four years after diagnosis
quality of life
Measured: four years after diagnosis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2005 (estimated)
- Study startJun 2003
- Primary completionJun 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for VasculitisStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 131 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development, Dutch Arthritis Association, Dutch Kidney Foundation
- Responsible party
- Principal investigator, J.S.F. Sanders, University Medical Center Groningen
- Investigators
- Coen A Stegeman, MD, PhD, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00128895
- Sponsor's protocol ID
- AZA-ANCA-1
- Status last verified
- Dec 2018
- First submitted
- 9 Aug 2005
- Last updated
- 13 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 27242368
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Relapses in PR3-ANCA-associated Vasculitis, a Tailored Approach
- ClinicalTrials.gov ID
- NCT00128895
- Acronym / sponsor ID
- AZA-ANCA-1
- Conditions
- Vasculitis
- Keywords
- Wegener's granulomatosis, ANCA, vasculitis, proteinase 3, ANCA-associated vasculitis, ANCA
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 131 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development, Dutch Arthritis Association, Dutch Kidney Foundation
- Study start
- Jun 2003
- Primary completion
- Jun 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 10 Aug 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| azathioprine, standard | Active comparator | Drug: azathioprinestandard azathioprine maintenance upto one year after diagnosis, subsequently tapering of azathioprine with 25 mg per 3 months |
| azathioprine, longterm | Experimental | Drug: azathioprinelongterm maintenance with azathioprine upto four years after diagnosis, subsequently azathioprine will be tapered with 25 mg per 3 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Newly diagnosed ANCA-associated vasculitis
- PR3-ANCA antibodies present
- Indication for treatment with cyclophosphamide and prednisolone
Key exclusion criteria (1 listed)
- Intolerance or allergy to azathioprine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| azathioprineazathioprine 2 mg/kg oral once daily, duration according to arm | Drug | azathioprine, longterm, azathioprine, standard |
Primary outcome
disease free survival
Time frame: four years after diagnosis
4 secondary outcomes
cumulative organ damage
Time frame: four years after diagnosis
side-effects
Time frame: up to four years after diagnosis
cumulative dosages of cyclophosphamide, prednisolone and azathioprine
Time frame: up to four years after diagnosis
quality of life
Time frame: four years after diagnosis
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2018.
- Results publication: PubMed 27242368Sanders 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Coen A Stegeman, MD, PhD principal investigator
University Medical Center Groningen
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing azathioprine in people with Vasculitis, run by University Medical Center Groningen at 8 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
disease free survival (time frame: four years after diagnosis). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00128895, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2018.