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Efficacy Study of Two Treatments in the Remission of Vasculitis (MAINRITSAN)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00748644
First received: September 5, 2008
Last updated: August 2, 2013
Last verified: January 2012

September 5, 2008
August 2, 2013
October 2008
March 2013   (final data collection date for primary outcome measure)
Number of major relapse (BVAS>10) in each group at the end of the maintenance treatment (18 months treatment + 10 months follow-up) [ Time Frame: 28 months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00748644 on ClinicalTrials.gov Archive Site
  • To assess the number of adverse events and their severity in each group [ Time Frame: 28 months ] [ Designated as safety issue: Yes ]
  • Number of patients with ANCA in each group [ Time Frame: 28 months ] [ Designated as safety issue: No ]
  • mortality rate in each group [ Time Frame: 28 months ] [ Designated as safety issue: No ]
  • number of minor relapse in each group [ Time Frame: 28 months ] [ Designated as safety issue: No ]
  • Cumulated dose and the length of corticosteroid treatment in each group at 28 months [ Time Frame: 28 months ] [ Designated as safety issue: No ]
  • same criteria with an analysis at 6 months after the end of maintenance treatment [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Efficacy Study of Two Treatments in the Remission of Vasculitis
MAINtenance of Remission Using RITuximab in Systemic ANCA-associated Vasculitis

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

Randomized, controlled, national, multicenter, prospective study to compare between azathioprine (conventional therapy) and rituximab in patients with systemic ANCA-associated vasculitis, in remission (achieved with an induction treatment combining corticosteroids and an immunosuppressant, mainly intravenous pulses of cyclophosphamide, and plasma exchanges and/or polyvalent immunoglobulins when indicated) after the first flare of the disease (new diagnosis) or after a relapse. It is planned to stratify patients by first flare (66% of the patients) or relapse (33% of the patients). Patients complying with the inclusion criteria may be included when they are in remission from their vasculitis. Patients who have already received biologics (antiCD20, antiTNFα) will not be included. Patients will be included at the time of remission and then randomized. They will receive maintenance treatment by azathioprine for 18 months or a rituximab infusion every 6 months until month 18 (i.e. a total of 4 infusions), at the dose of 375 mg/m2 (maximum dosage, 500 mg). ANCA status and CD19+ lymphocyte count will be monitored but will not be used to adjust therapy. After the 18 month length of maintenance phase, i.e. after stopping immunosuppressive maintenance therapy, patients will be followed for an additional 10 month period. Patients with Wegener's granulomatosis will be prescribed cotrimoxazole 160/800 tid (for 2 additional years).

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Wegener's Granulomatosis,
  • Microscopic Polyangiitis
  • Drug: Rituximab

    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.

  • Drug: Azathioprine

    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.

  • Experimental: 1
    Experimental drug = rituximab for maintenance
    Intervention: Drug: Rituximab
  • Active Comparator: 2
    Comparator drug = azathioprine for maintenance
    Intervention: Drug: Azathioprine
Guillevin L, Pagnoux C, Karras A, Khouatra C, Aumaître O, Cohen P, Maurier F, Decaux O, Ninet J, Gobert P, Quémeneur T, Blanchard-Delaunay C, Godmer P, Puéchal 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
117
June 2013
March 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • patients presenting a systemic disease receiving protocolized treatments (azathioprine, rituximab) which could have unexpected and inappropriate side effects.
  • Participation in another clinical research protocol during the 4 weeks before inclusion.
  • Any medical or psychiatric disorder which, in the investigator's opinion, may prevent the administration of treatment and patient follow-up according to the protocol, and/or which may expose the patient to a too greater risk of an adverse effect.
  • No social security
  • Churg and Strauss syndrome
  • viral, bacterial or fungic or mycobacterial infection uncontrolled in the 4 weeks before the inclusion
  • history of deep tissue infection (fasciitis, osteomyelitis, septic arthritis)in the first year before the inclusion
  • History of chronic and severe or recurrent infection or history of preexisting disease predisposing to severe infection
  • Severe immunodepression
  • Administration of live vaccine in the four weeks before inclusion
  • severe chronic obstructive pulmonary diseases (VEMS < 50 % or dyspnea grade III)
  • chronic heart failure stade III and IV (NYHA)
  • History of recent acute coronary syndrome
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00748644
P 070703
Yes
Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
Not Provided
Study Director: Loic Guillevin, MD, PhD French Vasculitis Study Group
Assistance Publique - Hôpitaux de Paris
January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP