Efficacy Study of Two Treatments in the Remission of Vasculitis

NCT00748644 | Completed Phase 3 DMC

• 1 other identifier: P 070703
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 1

Brief Summary

Study of the efficacy of rituximab for maintenance treatment in systemic ANCA-associated vasculitis: prospective, multicenter, controlled, randomized comparative study of rituximab versus azathioprine

Conditions

Wegener Granulomatosis; Microscopic Polyangiitis

Keywords

Wegener's granulomatosis,; microscopic polyangiitis,; ANCA-associated vasculitis,; rituximab,; azathioprine

Outcome Measures

Primary Outcomes (1)

• Number of major relapse (BVAS>10) in each group at the end of the maintenance treatment (18 months treatment + 10 months follow-up)

  28 months

Secondary Outcomes (6)

• To assess the number of adverse events and their severity in each group

  28 months

• Number of patients with ANCA in each group

  28 months

• mortality rate in each group

  28 months

• number of minor relapse in each group

  28 months

• Cumulated dose and the length of corticosteroid treatment in each group at 28 months

  28 months

Study Arms (2)

1

EXPERIMENTAL

Experimental drug = rituximab for maintenance

Drug: Rituximab

2

ACTIVE COMPARATOR

Comparator drug = azathioprine for maintenance

Drug: Azathioprine

Interventions

Rituximab DRUG

rituximab infusion will be performed at J1, J15, M6, M12 and M18(i.e. a total of 5 infusions), at the dose of 500 mg at a fixed dosage. All patients received corticosteroids, starting from induction with prednisone (or equivalent) at a dose of 1 mg/kg/day with gradual tapering according to a regimen adjusted to body weight over a mean of 18 months since diagnosis.

1

Azathioprine DRUG

azathioprine (2 mg/kg/d) for 12 months, then progressively tapered until its discontinuation at month 22. All patients received corticosteroids, starting from induction with prednisone (or equivalent) at a dose of 1 mg/kg/day with gradual tapering according to a regimen adjusted to body weight over a mean of 18 months since diagnosis.

2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Wegener's granulomatosis Or microscopic polyangiitis complying Or kidney-limited disease With or without detectable ANCA (anti-neutrophil cytoplasmic antibodies) at the time of diagnosis or relapse, and at remission.
• Who have achieved remission using a treatment combining corticosteroids and an immunosuppressive agent according to current French guideline, including corticosteroids, cyclophosphamide IV or oral (the use of another immunosuppressant is allowed, according to the current French guidelines, as well as plasma exchanges and/or IV immunoglobulins).
• Interval of 1 month between the end of the immunosuppressant treatment and the randomization time
• Age \> 18 years and \< 75 years when the diagnosis is confirmed.
• Informed and having signed the consent form to take part in the study.

You may not qualify if:

• Other systemic vasculitis
• Secondary vasculitis (following neoplastic disease or an infection in particular)·
• Induction treatment with a regimen not corresponding to that recommended in France.
• Patient who has not achieved remission.·
• Patient who has already received a treatment by biological agents (monoclonal antibody - antiCD20 or antiTNFα).
• Incapacity or refusal to understand or sign the informed consent form.
• Incapacity or refusal to adhere to treatment or perform the follow-up examinations required by the study. Non-compliance·
• Allergy, documented hypersensitivity or contraindication to the study medication (cyclophosphamide, corticosteroids, azathioprine, rituximab),
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
• Patients receiving allopurinol cannot be included if the allopurinol must absolutely be maintained.
• Pregnancy, breastfeeding. Women of childbearing age must use a reliable method of contraception throughout the duration of immunosuppressive treatment up to 1 year after the last infusion of rituximab
• Infection by HIV, HCV or HBV
• Progressive, uncontrolled infection requiring a prolonged treatment (tuberculosis, HIV infection, etc.).
• Severe infection declared during the 3 months before randomization (CMV, HBV, HHV8, HCV, HIV, tuberculosis).
• Progressive cancer or malignant blood disease diagnosed during the 5 years before the diagnosis of vasculitis. Patients suffering from non-metastatic prostate cancer or those cured of a cancer or a malignant blood disorder for more than 5 years and not taking any antineoplastic agents for more than 5 years may be included.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Hopital Cochin

Paris, 75014, France

Location

Related Publications (4)

• Pugnet G, Pagnoux C, Terrier B, Perrodeau E, Puechal X, Karras A, Khouatra C, Aumaitre O, Cohen P, Maurier F, Decaux O, Ninet J, Gobert P, Quemeneur T, Blanchard-Delaunay C, Godmer P, Carron PL, Hatron PY, Limal N, Hamidou M, Ducret M, Daugas E, Papo T, Bonnotte B, Mahr A, Ravaud P, Mouthon L, Guillevin L; French Vasculitis Study Group. Rituximab versus azathioprine for ANCA-associated vasculitis maintenance therapy: impact on global disability and health-related quality of life. Clin Exp Rheumatol. 2016 May-Jun;34(3 Suppl 97):S54-9. Epub 2016 Mar 25.

  PMID: 27049404 RESULT

• Guillevin L, Pagnoux C, Karras A, Khouatra C, Aumaitre O, Cohen P, Maurier F, Decaux O, Ninet J, Gobert P, Quemeneur T, Blanchard-Delaunay C, Godmer P, Puechal X, Carron PL, Hatron PY, Limal N, Hamidou M, Ducret M, Daugas E, Papo T, Bonnotte B, Mahr A, Ravaud P, Mouthon L; French Vasculitis Study Group. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med. 2014 Nov 6;371(19):1771-80. doi: 10.1056/NEJMoa1404231.

  PMID: 25372085 RESULT

• Romand X, Paclet MH, Chuong MV, Gaudin P, Pagnoux C, Guillevin L, Terrier B, Baillet A. Serum calprotectin and renal function decline in ANCA-associated vasculitides: a post hoc analysis of MAINRITSAN trial. RMD Open. 2023 Oct;9(4):e003477. doi: 10.1136/rmdopen-2023-003477.

  PMID: 37903568 DERIVED

• Terrier B, Pagnoux C, Perrodeau E, Karras A, Khouatra C, Aumaitre O, Cohen P, Decaux O, Desmurs-Clavel H, Maurier F, Gobert P, Quemeneur T, Blanchard-Delaunay C, Bonnotte B, Carron PL, Daugas E, Ducret M, Godmer P, Hamidou M, Lidove O, Limal N, Puechal X, Mouthon L, Ravaud P, Guillevin L; French Vasculitis Study Group. Long-term efficacy of remission-maintenance regimens for ANCA-associated vasculitides. Ann Rheum Dis. 2018 Aug;77(8):1150-1156. doi: 10.1136/annrheumdis-2017-212768. Epub 2018 May 3.

  PMID: 29724729 DERIVED

Related Links

• Website of the French Vasculitis Study Group

MeSH Terms

Conditions

Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Interventions

Rituximab; Azathioprine

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Loic Guillevin, MD, PhD

  French Vasculitis Study Group

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: September 5, 2008
• First Posted: September 8, 2008
• Study Start: October 1, 2008
• Primary Completion: March 1, 2013
• Study Completion: June 1, 2013
• Last Updated: November 20, 2025

Record last verified: 2025-10

Locations

FR (1)