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

NCT00307645 | Terminated Phase 3

• 1 other identifier: P991003
• Study Type: interventional
• Target: 160
• Locations: 2 countries
• Sites: 2

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. 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

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

Outcome Measures

Primary Outcomes (3)

• 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

Interventions

Cyclophosphamide DRUG

Mycophenolate mofetil DRUG

Azathioprine DRUG

Prednisone (and methylprednisolone) DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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\*
• 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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (2)

Hopital Cochin

Paris, 75679, France

Location

Addenbrooke's Hospital - Departement of Medecine

Cambridge, CB2 2SP, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 28592297 DERIVED

• Hiemstra 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.

  PMID: 21060104 DERIVED

MeSH Terms

Conditions

Microscopic Polyangiitis

Interventions

Cyclophosphamide; Mycophenolic Acid; Azathioprine; Prednisone; Methylprednisolone

Condition Hierarchy (Ancestors)

Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Thionucleosides; Sulfur Compounds; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Prednisolone; Pregnadienetriols

Study Officials

• Loïc GUILLEVIN, MD,PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 27, 2006
• First Posted: March 28, 2006
• Study Start: May 1, 2003
• Study Completion: August 1, 2009
• Last Updated: April 10, 2006

Record last verified: 2003-03

Locations

FR (1); GB (1)