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

April 7, 2006 updated by: Assistance Publique - Hôpitaux de Paris

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment

160

Phase

  • Phase 3

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

  • France
      • Paris, France, 75679
        • Hôpital COCHIN
  • United Kingdom
      • Cambridge, United Kingdom, CB2 2SP
        • Addenbrooke's Hospital - Departement of Medecine

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

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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 Outcome Measures

Outcome Measure
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

Collaborators and Investigators

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

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Loïc GUILLEVIN, MD,PhD, Assistance Publique - Hôpitaux de Paris

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

May 1, 2003

Study Completion

August 1, 2009

Study Registration Dates

First Submitted

March 27, 2006

First Submitted That Met QC Criteria

March 27, 2006

First Posted (Estimate)

March 28, 2006

Study Record Updates

Last Update Posted (Estimate)

April 10, 2006

Last Update Submitted That Met QC Criteria

April 7, 2006

Last Verified

March 1, 2003

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P991003

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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