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

March 1, 2018 updated by: Assistance Publique - Hôpitaux de Paris

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

117

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75014
        • Hopital Cochin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Experimental drug = rituximab for maintenance
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.
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 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
28 months

Secondary Outcome Measures

Outcome Measure
Time Frame
To assess the number of adverse events and their severity in each group
Time Frame: 28 months
28 months
Number of patients with ANCA in each group
Time Frame: 28 months
28 months
mortality rate in each group
Time Frame: 28 months
28 months
number of minor relapse in each group
Time Frame: 28 months
28 months
Cumulated dose and the length of corticosteroid treatment in each group at 28 months
Time Frame: 28 months
28 months
same criteria with an analysis at 6 months after the end of maintenance treatment
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Study Director: Loic Guillevin, MD, PhD, French Vasculitis Study Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2008

Primary Completion (Actual)

March 1, 2013

Study Completion (Actual)

June 1, 2013

Study Registration Dates

First Submitted

September 5, 2008

First Submitted That Met QC Criteria

September 5, 2008

First Posted (Estimate)

September 8, 2008

Study Record Updates

Last Update Posted (Actual)

March 2, 2018

Last Update Submitted That Met QC Criteria

March 1, 2018

Last Verified

January 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P 070703

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Microscopic Polyangiitis

Clinical Trials on Rituximab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Türkiye

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe