Comparison Study of Two Rituximab Regimens in the Remission of ANCA Associated Vasculitis (MAINRITSAN 2)
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ClinicalTrials.gov Identifier: NCT01731561 |
Recruitment Status :
Completed
First Posted : November 22, 2012
Last Update Posted : March 2, 2018
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Condition or disease | Intervention/treatment | Phase |
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Granulomatosis With Polyangiitis Microscopic Polyangiitis Renal Limited Forms | Drug: Rituximab (Arm B) Drug: Rituximab (Arm A) | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 166 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | MAINtenance of Remission Using RITuximab in Systemic ANCA-associated Vasculitis II |
Actual Study Start Date : | November 16, 2012 |
Actual Primary Completion Date : | April 5, 2016 |
Actual Study Completion Date : | April 5, 2016 |

Arm | Intervention/treatment |
---|---|
Experimental: Rituximab infusion according biological parameters
Rituximab infusion based on ANCA and CD19 lymphocytes
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Drug: Rituximab (Arm B)
Rituximab infusion will be performed at D1 then ANCA status and CD19+ lymphocyte count will be monitored every 3 months, and patients will receive new 500 mg rituximab infusions either if CD19 are > to 0/mm3, or if ANCA are positive again or if ANCA titer significantly raises. 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: Systematic rituximab infusion
Semestrial rituximab infusion until 18 months
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Drug: Rituximab (Arm A)
Rituximab infusion will be performed at D1, D15, 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. |
- Number of relapses [ Time Frame: at 28 months ]Number of relapses (BVAS>0) majors and minors in each group at the end of the maintenance treatment (18 months treatment + 10 months follow-up)
- Number of patients with ANCA (Anti-Neutrophil Cytoplasmatic Antibodies) [ Time Frame: at 28 months ]Number of patients with ANCA in each group
- Number of adverse events [ Time Frame: at 28 months ]To assess the number of adverse events and their severity in each group
- Mortality rate [ Time Frame: at 28 months ]To assess mortality rate in each group
- Number of minor relapse [ Time Frame: at 28 months ]number of minor relapse in each group
- Cumulated dose of corticosteroid treatment [ Time Frame: at 28 months ]Cumulated dose of corticosteroid treatment in each group at 28 months
- Number and severity of damages [ Time Frame: at 28 months ]Number and severity of damages in each group
- Evolution of ANCA and the link of the clinical events [ Time Frame: at 28 months ]Evolution of ANCA in each group and the link of the clinical events
- Distribution of events by severity [ Time Frame: at 28 months ]Distribution of events by severity and it will be assigned to the drug and its mode of administration and/or the severity of the disease (in each group).
- Length of corticosteroid treatment [ Time Frame: at 28 months ]The length of corticosteroid treatment in each group at 28 months
- Rate of B-Lymphocytes CD-19 and the link of the clinical events [ Time Frame: at 28 months ]The rate of B-Lymphocytes CD-19 and the link of the clinical events
- Evolution of gammaglobulins [ Time Frame: at 28 months ]
- Quality of life : SF36 (The Short Form (36) Health Survey) [ Time Frame: at 28 months ]
- Functional capacities : HAQ (Health Assessment Questionnaire) [ Time Frame: at 28 months ]

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Granulomatosis with Polyangiitis 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, 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, or rituximab).
- Interval of 1 month between the end of the immunosuppressant treatment and the randomization time if cyclophosphamide or methotrexate were used, interval between 4 and 6 months if rituximab was used
- Age > 18 years without age limit higher 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.
- 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.
- 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.
- 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, unrelated to vasculitis

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01731561
France | |
Cochin Hospital | |
Paris, France, 75014 |
Study Chair: | Loic Guillevin, MD, PhD | Cochin Hospital, Paris, France | |
Study Chair: | Pierre Charles, MD | Institut mutualiste, Paris, France |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Assistance Publique - Hôpitaux de Paris |
ClinicalTrials.gov Identifier: | NCT01731561 |
Other Study ID Numbers: |
P110146 2012-001963-66 ( EudraCT Number ) |
First Posted: | November 22, 2012 Key Record Dates |
Last Update Posted: | March 2, 2018 |
Last Verified: | February 2018 |
Granulomatosis with Polyangiitis Microscopic polyangiitis Renal limited forms ANCA-associated vasculitis Rituximab |
Granulomatosis with Polyangiitis Microscopic Polyangiitis Vasculitis Systemic Vasculitis Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Vascular Diseases Cardiovascular Diseases Lung Diseases, Interstitial Lung Diseases Respiratory Tract Diseases Autoimmune Diseases Immune System Diseases |
Cerebral Small Vessel Diseases Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Rituximab Antineoplastic Agents, Immunological Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents |