We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

IMPROVE: Mycophenolate Mofetil Versus Azathioprine for Maintenance Therapy in ANCA Associated Systemic Vasculitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00307645
Recruitment Status : Terminated
First Posted : March 28, 2006
Last Update Posted : April 10, 2006
Information provided by:
Assistance Publique - Hôpitaux de Paris

Brief 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.


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

Condition or disease Intervention/treatment Phase
ANCA Associated Systemic Vasculitis Including Wegener's Granulomatosis and Microscopic Polyangiitis and Renal Limited Vasculitis Drug: Cyclophosphamide Drug: Mycophenolate mofetil Drug: Azathioprine Drug: Prednisone (and methylprednisolone) Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Mycophenolate Mofetil Versus Azathioprine for Maintenance Therapy in ANCA Associated Systemic Vasculitis
Study Start Date : May 2003
Study Completion Date : August 2009

Primary Outcome Measures :
  1. the disease-free period, defined as the time between the beginning
  2. of the maintenance therapy (AZA or MMF) and the first relapse (minor or major)
  3. or the end of the protocol (at 48 months)

Secondary Outcome Measures :
  1. relapse rate
  2. rate of side-effects and intolerance
  3. cumulative doses (AZA, CS, MMF)
  4. AUC for BVAS, SF-36 or VDI
  5. Evolution of titers of ANCA and CRP

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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.

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): NCT00307645

Layout table for location information
Hopital Cochin
Paris, France, 75679
United Kingdom
Addenbrooke's Hospital - Departement of Medecine
Cambridge, United Kingdom, CB2 2SP
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Layout table for investigator information
Principal Investigator: Loïc GUILLEVIN, MD,PhD Assistance Publique - Hôpitaux de Paris
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
ClinicalTrials.gov Identifier: NCT00307645    
Other Study ID Numbers: P991003
First Posted: March 28, 2006    Key Record Dates
Last Update Posted: April 10, 2006
Last Verified: March 2003
Keywords provided by Assistance Publique - Hôpitaux de Paris:
ANCA associated systemic vasculitis
Maintenance therapy
Mycophenolate mofetil
Additional relevant MeSH terms:
Layout table for MeSH terms
Microscopic Polyangiitis
Systemic Vasculitis
Vascular Diseases
Cardiovascular Diseases
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Autoimmune Diseases
Immune System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents