Systemic Wegener's GranulomatosisPhase 3NCT00349674
WEGENT - Comparison of Methotrexate or Azathioprine as Maintenance Therapy for ANCA-Associated Vasculitides
A Phase 3 study testing Azathioprine: 2 mg/kg/day and methotrexate 0.3 mg/kg/week, to a maximum and optimal dose of 25 mg/week in people with Systemic Wegener's Granulomatosis, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Remission of ANCA-associated vasculitis can be obtained in approximately 80% of the patients with a combination of corticosteroids and cyclophosphamide. However, relapses are frequent. This point warrants the prescription of a maintenance treatment with a less toxic immunosuppressant for several months to years. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Systemic Wegener's Granulomatosis
- What is being tested?
- Azathioprine: 2 mg/kg/day and methotrexate 0.3 mg/kg/week, to a maximum and optimal dose of 25 mg/week
- How many people
- 126 participants
- Where
- 1 siteFrance
- Study dates
- Jan 1999to not given
- Phase
- Phase 3
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged over 18 years-old with newly diagnosed systemic Wegener's granulomatosis,
- microscopic polyangitis with at least one factor of poor prognosis according to the five factors score (proteinuria > 1 g/day, renal insufficiency defined as a serum creatininemia > 140 µmol/L, specific cardiomyopathy, gastrointestinal tract and/or CNS involvement).
Who cannot join
- MPA patients with no poor prognosis factor;
- localized WG;
- relapse of previously known WG or MPA;
- treatment with corticosteroids for more than 1 month prior to diagnosis and start of immunosuppressant;
- co-existence of another multi-system autoimmune disease;
- malignancy (unless considered in complete remission and with no therapy for at least 3 years);
- contra-indication to corticosteroids or study immunosuppressants; pregnancy or no use of contraception in non-menopaused women;
- infection with human immunodeficiency virus; mental or physical disturbances not permitting to give consent.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treatment of ANCA-Associated Vasculitides : Corticosteroids and Pulse Cyclophosphamide Followed by Maintenance Therapy With Methotrexate or Azathioprine: a Prospective Multicenter Randomized Trial
Remission of ANCA-associated vasculitis can be obtained in approximately 80% of the patients with a combination of corticosteroids and cyclophosphamide. However, relapses are frequent. This point warrants the prescription of a maintenance treatment with a less toxic immunosuppressant for several months to years. The optimal drug in this indication is not determine. We decided therefore to compare the 2 most used drugs in this indication. Induction therapy consists in the combination of corticosteroids and intravenous cyclophosphamide pulses. Corticotherapy consisted first in one daily methylprednisolone pulse, for 1 to 3 days, followed by oral prednisolone at the dose of 1 mg/kg/d for 3 weeks, then progressively tapered and stopped at the 18th month from the diagnosis. Cyclophosphamide is administered every 2 weeks for the first 3 bolus (0.6 g/m2 - D1, 15 and 30), then every 3 weeks (0.7 g/m2). Once remission is achieved, patients receive 3 additional bolus (0.7 g/m2). At that time, patients are randomized for a maintenance treatment with azathioprine (2 mg/kg/d, orally) or oral methotrexate (starting at the dose of 0.3 mg/kg/wk, then progressively increased every weeks by 2.5mg, if necessary, to a maximum and optimal dose of 25 mg/wk) for 12 months.
- Conditions
- Systemic Wegener's Granulomatosis
- Being tested
- Azathioprine: 2 mg/kg/day, methotrexate 0.3 mg/kg/week, to a maximum and optimal dose of 25 mg/week
- Keywords
- Wegener's granulomatosis,, microscopic polyangiitis,, ANCA-associated vasculitis,, methotrexate,, azathioprine
- Medical subject headings
- Granulomatosis with Polyangiitis, Microscopic 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.
Azathioprine: 2 mg/kg/dayDrug
methotrexate 0.3 mg/kg/week, to a maximum and optimal dose of 25 mg/weekDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety/Efficacy
Frequency of severe adverse events in each arm. Hypothesis based upon NIH data was a rate of 6% severe adverse event with methotrexate compared to 30% with azathioprine (24% in one study on RA and 46% in one study on Sjögren syndrome).
Evaluation was planned after the last included patient has completed the assigned trial regimen (after 12 months of maintenance regimen or because of drug withdrawal).
Secondary outcomes (5)
Relapse-free survival rate.
Cumulative event-free survival rate (adverse event- and relapse-free survival rate).
Health quality assessment using HAQ and SF36.
Efficacy of induction therapy with pulsed cyclophosphamide.
Second evaluation of the same outcome parameters is planned 5 years after the last included patient has completed the assigned trial regimen.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2006 (estimated)
- Study startJan 1999
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 Systemic Wegener's GranulomatosisStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe 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 3
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 126 participants
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Investigators
- Jean-François CORDIER, MD, Principal investigator, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00349674
- Sponsor's protocol ID
- 97.129
- Status last verified
- Oct 2007
- First submitted
- 6 Jul 2006
- Last updated
- 10 Oct 2007
- Results posted
- No
Publications
Pagnoux C, Mahr A, Hamidou MA, Boffa JJ, Ruivard M, Ducroix JP, Kyndt X, Lifermann F, Papo T, Lambert M, Le Noach J, Khellaf M, Merrien D, Puechal X, Vinzio S, Cohen P, Mouthon L, Cordier JF, Guillevin L; French Vasculitis Study Group. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med. 2008 Dec 25;359(26):2790-803. doi: 10.1056/NEJMoa0802311.
PubMed 19109574
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of ANCA-Associated Vasculitides : Corticosteroids and Pulse Cyclophosphamide Followed by Maintenance Therapy With Methotrexate or Azathioprine: a Prospective Multicenter Randomized Trial
- ClinicalTrials.gov ID
- NCT00349674
- Acronym / sponsor ID
- 97.129
- Conditions
- Systemic Wegener's Granulomatosis
- Keywords
- Wegener's granulomatosis,, microscopic polyangiitis,, ANCA-associated vasculitis,, methotrexate,, azathioprine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 126 participants
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- Jan 1999
- First posted
- 7 Jul 2006 (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.
Remission of ANCA-associated vasculitis can be obtained in approximately 80% of the patients with a combination of corticosteroids and cyclophosphamide. However, relapses are frequent. This point warrants the prescription of a maintenance treatment with a less toxic immunosuppressant for several months to years. The optimal drug in this indication is not determine. We decided therefore to compare the 2 most used drugs in this indication. Induction therapy consists in the combination of corticosteroids and intravenous cyclophosphamide pulses. Corticotherapy consisted first in one daily methylprednisolone pulse, for 1 to 3 days, followed by oral prednisolone at the dose of 1 mg/kg/d for 3 weeks, then progressively tapered and stopped at the 18th month from the diagnosis. Cyclophosphamide is administered every 2 weeks for the first 3 bolus (0.6 g/m2 - D1, 15 and 30), then every 3 weeks (0.7 g/m2). Once remission is achieved, patients receive 3 additional bolus (0.7 g/m2). At that time, patients are randomized for a maintenance treatment with azathioprine (2 mg/kg/d, orally) or oral methotrexate (starting at the dose of 0.3 mg/kg/wk, then progressively increased every weeks by 2.5mg, if necessary, to a maximum and optimal dose of 25 mg/wk) for 12 months.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients aged over 18 years-old with newly diagnosed systemic Wegener's granulomatosis,
- microscopic polyangitis with at least one factor of poor prognosis according to the five factors score (proteinuria > 1 g/day, renal insufficiency defined as a serum creatininemia > 140 µmol/L, specific cardiomyopathy, gastrointestinal tract and/or CNS involvement).
Key exclusion criteria (8 listed)
- MPA patients with no poor prognosis factor;
- localized WG;
- relapse of previously known WG or MPA;
- treatment with corticosteroids for more than 1 month prior to diagnosis and start of immunosuppressant;
- co-existence of another multi-system autoimmune disease;
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 |
|---|---|---|
| Azathioprine: 2 mg/kg/day | Drug | – |
| methotrexate 0.3 mg/kg/week, to a maximum and optimal dose of 25 mg/week | Drug | – |
Primary outcome
Safety/Efficacy
Frequency of severe adverse events in each arm. Hypothesis based upon NIH data was a rate of 6% severe adverse event with methotrexate compared to 30% with azathioprine (24% in one study on RA and 46% in one study on Sjögren syndrome).
Evaluation was planned after the last included patient has completed the assigned trial regimen (after 12 months of maintenance regimen or because of drug withdrawal).
5 secondary outcomes
Relapse-free survival rate.
Cumulative event-free survival rate (adverse event- and relapse-free survival rate).
Health quality assessment using HAQ and SF36.
Efficacy of induction therapy with pulsed cyclophosphamide.
Second evaluation of the same outcome parameters is planned 5 years after the last included patient has completed the assigned trial regimen.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2007.
- Derived from this study: PubMed 19109574Pagnoux C, Mahr A, Hamidou MA, Boffa JJ, Ruivard M, Ducroix JP, Kyndt X, Lifermann F, Papo T, Lambert M, Le Noach J, Khellaf M, Merrien D, Puechal X, Vinzio S, Cohen P, Mouthon L, Cordier JF, Guillevin L; French Vasculitis Study Group. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med. 2008 Dec 25;359(26):2790-803. doi: 10.1056/NEJMoa0802311.
- Related InfoLink provided by the sponsor.
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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.
Jean-François CORDIER, MD principal investigator
Hospices Civils de Lyon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Azathioprine: 2 mg/kg/day and methotrexate 0.3 mg/kg/week, to a maximum and optimal dose of 25 mg/week in people with Systemic Wegener's Granulomatosis, run by Hospices Civils de Lyon at 1 site in France.
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 2 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 10 Oct 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
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?
Safety/Efficacy. The study lists 3 primary outcomes in all. 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 NCT00349674, 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 10 Oct 2007.