ANCA Associated Systemic Vasculitis Including Wegener'sPhase 3NCT00307645
IMPROVE: Mycophenolate Mofetil Versus Azathioprine for Maintenance Therapy in ANCA Associated Systemic Vasculitis
A Phase 3 study testing Cyclophosphamide, Mycophenolate mofetil and Azathioprine in people with ANCA Associated Systemic Vasculitis Including Wegener's and Granulomatosis and Microscopic Polyangiitis and, run by Assistance Publique - Hôpitaux de Paris at 2 sites in 2 countries.
Trial summary
The aim of IMPROVE is to define the optimal maintenance therapy for ANCA-associated vasculitides (AASV) by comparing the AZA (standard regimen) with MMF in terms of efficacy, i.e. in preventing relapses. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ANCA Associated Systemic Vasculitis Including Wegener's, Granulomatosis and Microscopic Polyangiitis and, Renal Limited Vasculitis
- What is being tested?
- Cyclophosphamide, Mycophenolate mofetil and Azathioprine
- How many people
- 160 participants
- Where
- 2 sitesin 2 countries
- Study dates
- May 2003to Aug 2009
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Newly diagnosed patients with WG, MPA or renal-limited vasculitis.
- ANCA positivity. ANCA positivity requires PR3-ANCA or a typical cANCA pattern by indirect immunofluorescence (IIF), preferably confirmed by anti-PR3 ELISA. MPO-ANCA determined by ELISA requires demonstration of pANCA, and pANCA by IIF requires confirmation by anti-MPO ELISA. Optionally, central review of ANCA serology can be performed.
- Age 18 to 75 years
Who cannot join
- Any cytotoxic drug within previous year, unless started within one months of entry and according to the protocol design
- Co-existence of another systemic autoimmune disease, e.g. SLE
- Hepatitis B or Hepatitis C infection
- HIV positivity
- Failure to achieve remission after 6 months of CYC therapy
- Failure to control progressive disease with induction protocol
Show all 12Show fewer
- Malignancy (usually exclude unless agreed with trial co-ordinator)
- Pregnancy or inadequate contraception
- Age below 18 and above 75 years*
- Endstage renal failure unless active extrarenal disease requires treatment (temporal dependency of hemodialysis is not an exclusion criterion)
- Inability for informed consent
- After discussion with the trial administrator, patients less than 18 years may be incorporated on separate application according to the appropriate local ethic committee.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United Kingdom1 site
Addenbrooke's Hospital - Departement of Medecine
Cambridge, CB2 2SP
About this study
Official title: Mycophenolate Mofetil Versus Azathioprine for Maintenance Therapy in ANCA Associated Systemic Vasculitis
The aim of IMPROVE is to define the optimal maintenance therapy for ANCA-associated vasculitides (AASV) by comparing the AZA (standard regimen) with MMF in terms of efficacy, i.e. in preventing relapses.
HYPOTHESIS :
MMF might be more effective than azathioprine as maintenance drug in AASV patients, reducing by 50% relapse rate, with a same frequency of adverse effects
Read the detailed description
AASV, including Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) and renal limited vasculitis (RLV), are progressive, multisystem, autoimmune diseases which require the prescription of immunosuppressive therapy. Treatment using corticosteroids and cytotoxic drugs has been standardised (ECSYSVASTRIAL project), but relapse rate remains high and treatment-related toxicity is non negligible. The IMPROVE trial aims to reduce this relapse rate by using mycophenolate mofetil (MMF) for maintenance therapy. The potential benefit of MMF has been suggested in a published open and uncontrolled study. Patients with newly diagnosed systemic AASV will be randomly assigned to receive either MMF or reference treatment with azathioprine (AZA), once remission has been obtained with cyclophosphamide and prednisone. MMF and AZA will be continued for a total of 42 months of therapy with concomitant prednisone dose tapering. The study will last 48 months. Hence, within the last 6 months of the study duration, the patients will not receive any immunosuppressive drugs.
The primary end-point will the disease-free period, taken as the period of time from remission until relapse or study end; secondary end-points will be adverse events, cumulative damage (assessed using damage score VDI) and immunosuppressive drug cumulative dose.
- Conditions
- ANCA Associated Systemic Vasculitis Including Wegener's, Granulomatosis and Microscopic Polyangiitis and, Renal Limited Vasculitis
- Being tested
- Cyclophosphamide, Mycophenolate mofetil, Azathioprine, Prednisone (and methylprednisolone)
- Keywords
- ANCA associated systemic vasculitis, Maintenance therapy, Azathioprine, Mycophenolate mofetil
- Medical subject headings
- Microscopic Polyangiitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
AzathioprineDrug
Prednisone (and methylprednisolone)Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
the disease-free period, defined as the time between the beginning
of the maintenance therapy (AZA or MMF) and the first relapse (minor or major)
or the end of the protocol (at 48 months)
Secondary outcomes (5)
relapse rate
rate of side-effects and intolerance
cumulative doses (AZA, CS, MMF)
AUC for BVAS, SF-36 or VDI
Evolution of titers of ANCA and CRP
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2006 (estimated)
- Study startMay 2003
- Study completionAug 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ANCA Associated Systemic Vasculitis Including Wegener'sStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 160 participants
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Investigators
- Loïc GUILLEVIN, MD,PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00307645
- Sponsor's protocol ID
- P991003
- Status last verified
- Mar 2003
- First submitted
- 27 Mar 2006
- Last updated
- 10 Apr 2006
- Results posted
- No
Publications
Morgan MD, Szeto M, Walsh M, Jayne D, Westman K, Rasmussen N, Hiemstra TF, Flossmann O, Berden A, Hoglund P, Harper L; European Vasculitis Society. Negative anti-neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapse. Arthritis Res Ther. 2017 Jun 7;19(1):129. doi: 10.1186/s13075-017-1321-1.
PubMed 28592297Hiemstra TF, Walsh M, Mahr A, Savage CO, de Groot K, Harper L, Hauser T, Neumann I, Tesar V, Wissing KM, Pagnoux C, Schmitt W, Jayne DR; European Vasculitis Study Group (EUVAS). Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial. JAMA. 2010 Dec 1;304(21):2381-8. doi: 10.1001/jama.2010.1658. Epub 2010 Nov 8.
PubMed 21060104
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mycophenolate Mofetil Versus Azathioprine for Maintenance Therapy in ANCA Associated Systemic Vasculitis
- ClinicalTrials.gov ID
- NCT00307645
- Acronym / sponsor ID
- P991003
- Conditions
- ANCA Associated Systemic Vasculitis Including Wegener's, Granulomatosis and Microscopic Polyangiitis and, Renal Limited Vasculitis
- Keywords
- ANCA associated systemic vasculitis, Maintenance therapy, Azathioprine, Mycophenolate mofetil
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 160 participants
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- May 2003
- Study completion
- Aug 2009
- First posted
- 28 Mar 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.
The aim of IMPROVE is to define the optimal maintenance therapy for ANCA-associated vasculitides (AASV) by comparing the AZA (standard regimen) with MMF in terms of efficacy, i.e. in preventing relapses.
HYPOTHESIS :
MMF might be more effective than azathioprine as maintenance drug in AASV patients, reducing by 50% relapse rate, with a same frequency of adverse effects
Detailed description
AASV, including Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) and renal limited vasculitis (RLV), are progressive, multisystem, autoimmune diseases which require the prescription of immunosuppressive therapy. Treatment using corticosteroids and cytotoxic drugs has been standardised (ECSYSVASTRIAL project), but relapse rate remains high and treatment-related toxicity is non negligible. The IMPROVE trial aims to reduce this relapse rate by using mycophenolate mofetil (MMF) for maintenance therapy. The potential benefit of MMF has been suggested in a published open and uncontrolled study. Patients with newly diagnosed systemic AASV will be randomly assigned to receive either MMF or reference treatment with azathioprine (AZA), once remission has been obtained with cyclophosphamide and prednisone. MMF and AZA will be continued for a total of 42 months of therapy with concomitant prednisone dose tapering. The study will last 48 months. Hence, within the last 6 months of the study duration, the patients will not receive any immunosuppressive drugs.
The primary end-point will the disease-free period, taken as the period of time from remission until relapse or study end; secondary end-points will be adverse events, cumulative damage (assessed using damage score VDI) and immunosuppressive drug cumulative dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
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 patients with WG, MPA or renal-limited vasculitis.
- ANCA positivity. ANCA positivity requires PR3-ANCA or a typical cANCA pattern by indirect immunofluorescence (IIF), preferably confirmed by anti-PR3 ELISA. MPO-ANCA determined by ELISA requires demonstration of pANCA, and pANCA by IIF requires confirmation by anti-MPO ELISA. Optionally, central review of ANCA serology can be performed.
- Age 18 to 75 years
Key exclusion criteria (12 listed)
- Any cytotoxic drug within previous year, unless started within one months of entry and according to the protocol design
- Co-existence of another systemic autoimmune disease, e.g. SLE
- Hepatitis B or Hepatitis C infection
- HIV positivity
- Failure to achieve remission after 6 months of CYC therapy
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 |
|---|---|---|
| Cyclophosphamide | Drug | – |
| Mycophenolate mofetil | Drug | – |
| Azathioprine | Drug | – |
| Prednisone (and methylprednisolone) | Drug | – |
Primary outcome
the disease-free period, defined as the time between the beginning
of the maintenance therapy (AZA or MMF) and the first relapse (minor or major)
or the end of the protocol (at 48 months)
5 secondary outcomes
relapse rate
rate of side-effects and intolerance
cumulative doses (AZA, CS, MMF)
AUC for BVAS, SF-36 or VDI
Evolution of titers of ANCA and CRP
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 10 Apr 2006.
- Derived from this study: PubMed 28592297Morgan MD, Szeto M, Walsh M, Jayne D, Westman K, Rasmussen N, Hiemstra TF, Flossmann O, Berden A, Hoglund P, Harper L; European Vasculitis Society. Negative anti-neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapse. Arthritis Res Ther. 2017 Jun 7;19(1):129. doi: 10.1186/s13075-017-1321-1.
- Derived from this study: PubMed 21060104Hiemstra TF, Walsh M, Mahr A, Savage CO, de Groot K, Harper L, Hauser T, Neumann I, Tesar V, Wissing KM, Pagnoux C, Schmitt W, Jayne DR; European Vasculitis Study Group (EUVAS). Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial. JAMA. 2010 Dec 1;304(21):2381-8. doi: 10.1001/jama.2010.1658. Epub 2010 Nov 8.
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.
Loïc GUILLEVIN, MD,PhD principal investigator
Assistance Publique - Hôpitaux de Paris
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cyclophosphamide, Mycophenolate mofetil and Azathioprine in people with ANCA Associated Systemic Vasculitis Including Wegener's and Granulomatosis and Microscopic Polyangiitis and, run by Assistance Publique - Hôpitaux de Paris at 2 sites in 2 countries.
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 12 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 10 Apr 2006. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France, United Kingdom. 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?
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?
the disease-free period, defined as the time between the beginning. 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 NCT00307645, which also lists 2 linked publications.
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 Apr 2006; AzTrials last refreshed its copy on 7 Nov 2026.