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

This study has been terminated.
Sponsor:
Information provided by:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00307645
First received: March 27, 2006
Last updated: April 7, 2006
Last verified: March 2003
  Purpose

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


Condition Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Mycophenolate Mofetil Versus Azathioprine for Maintenance Therapy in ANCA Associated Systemic Vasculitis

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • 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:
  • 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

Estimated Enrollment: 160
Study Start Date: May 2003
Estimated Study Completion Date: August 2009
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00307645

Locations
France
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
Investigators
Principal Investigator: Loïc GUILLEVIN, MD,PhD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided by Assistance Publique - Hôpitaux de Paris

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00307645     History of Changes
Other Study ID Numbers: P991003
Study First Received: March 27, 2006
Last Updated: April 7, 2006
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
ANCA associated systemic vasculitis
Maintenance therapy
Azathioprine
Mycophenolate mofetil

Additional relevant MeSH terms:
Vasculitis
Systemic Vasculitis
Microscopic Polyangiitis
Vascular Diseases
Cardiovascular Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Autoimmune Diseases
Immune System Diseases
Azathioprine
Cyclophosphamide
Mycophenolate mofetil
Methylprednisolone Hemisuccinate
Prednisolone
Mycophenolic Acid
Prednisone
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 01, 2014