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History of Changes for Study: NCT00748644
Efficacy Study of Two Treatments in the Remission of Vasculitis (MAINRITSAN)
Latest version (submitted March 1, 2018) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 September 5, 2008 None (earliest Version on record)
2 December 1, 2008 Recruitment Status, Study Status, Contacts/Locations and Eligibility
3 April 1, 2009 Study Status, Eligibility and Arms and Interventions
4 September 29, 2009 Study Status and Study Identification
5 February 19, 2010 Study Status and Arms and Interventions
6 February 9, 2011 Recruitment Status, Contacts/Locations, Study Status and Study Design
7 March 29, 2011 Study Status, Eligibility and Sponsor/Collaborators
8 January 25, 2012 Sponsor/Collaborators and Study Status
9 August 2, 2013 Recruitment Status, Study Status and Study Design
10 March 1, 2018 Study Status and Conditions
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Study NCT00748644
Submitted Date:  September 5, 2008 (v1)

Open or close this module Study Identification
Unique Protocol ID: P 070703
Brief Title: Efficacy Study of Two Treatments in the Remission of Vasculitis (MAINRITSAN)
Official Title: MAINtenance of Remission Using RITuximab in Systemic ANCA-Associated Vasculitis
Secondary IDs:
Open or close this module Study Status
Record Verification: August 2008
Overall Status: Not yet recruiting
Study Start: October 2008
Primary Completion: March 2013 [Anticipated]
Study Completion: June 2013 [Anticipated]
First Submitted: September 5, 2008
First Submitted that
Met QC Criteria:
September 5, 2008
First Posted: September 8, 2008 [Estimate]
Last Update Submitted that
Met QC Criteria:
September 5, 2008
Last Update Posted: September 8, 2008 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Assistance Publique - Hôpitaux de Paris
Responsible Party:
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
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
Detailed Description: 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).
Open or close this module Conditions
Conditions: Wegener's Granulomatosis,
Microscopic Polyangiitis
Keywords: Wegener's granulomatosis,
microscopic polyangiitis,
ANCA-associated vasculitis,
rituximab,
azathioprine
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 112 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: 1
Experimental drug = rituximab for maintenance
Drug: Rituximab

rituximab infusion every 6 months starting from remission until month 18 (i.e. a total of 4 infusions), at the dose of 375 mg/m2 (maximum dosage, 500 mg).

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.

Active Comparator: 2
Comparator drug = azathioprine for maintenance
Drug: Azathioprine

azathioprine (2 mg/kg/d) for 12 months, then progressively tapered until its discontinuation at month 18.

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.

Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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 ]

Secondary Outcome Measures:
1. To assess the number of adverse events and their severity in each group
[ Time Frame: 28 months ]

2. Number of patients with ANCA in each group
[ Time Frame: 28 months ]

3. mortality rate in each group
[ Time Frame: 28 months ]

4. number of minor relapse in each group
[ Time Frame: 28 months ]

5. Cumulated dose and the length of corticosteroid treatment in each group at 28 months
[ Time Frame: 28 months ]

6. same criteria with an analysis at 6 months after the end of maintenance treatment
[ Time Frame: 24 months ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 75 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

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).
  • Age > 18 years and < 75 years.
  • 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.
  • Patient with another systemic disease for which the treatments used may cause unforeseeable 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
  • Primitive or secondary Immunodeficiency (active or inactive)
  • Administration of live vaccine in the four weeks before inclusion
  • all treatments responsible of lymphopenia
  • 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
Open or close this module Contacts/Locations
Central Contact Person: Loic Guillevin, MD, PhD
Telephone: 0033158411321
Email: loic.guillevin@cch.aphp.fr
Central Contact Backup: Christian Pagnoux, MD
Telephone: 0033158411461
Email: christian.pagnoux@cch.aphp.fr
Study Officials: Loic Guillevin, MD, PhD
Study Director
French Vasculitis Study Group
Locations: France
Hopital Cochin Pole de Medecine
Paris, France, 75014
Contact:Contact: Loic Guillevin, MD, PhD 0033158411321 loic.guillevin@cch.aphp.fr
Contact:Contact: Raphaƫl Serreau, MD, PhD 0033158411180 raphael.serreau@cch.aphp.fr
Contact:Principal Investigator: Loic Guillevin, MD, PhD
Contact:Sub-Investigator: Christian Pagnoux, MD
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links: Description: Website of the French Vasculitis Study Group
Available IPD/Information:

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