Maintenance of Remission With Rituximab Versus Azathioprine for Newly-diagnosed or Relapsing Eosinophilic Granulomatosis With Polyangiitis. (MAINRITSEG)

November 17, 2025 updated by: Assistance Publique - Hôpitaux de Paris

MAINtenance of Remission With RITuximab Versus Azathioprine for Patients With Newly-diagnosed or Relapsing Eosinophilic Granulomatosis With Polyangiitis. A Prospective, Randomized, Controlled, Double-blind Study: the MAINRITSEG Trial

The purpose of this study is to investigate, after achievement of remission, the efficacy of rituximab compared with azathioprine maintenance therapy on duration of remission, in patients with relapsing or newly-diagnosed Eosinophilic granulomatosis with polyangiitis EPGA receiving standard of care therapy including glucocorticoid therapy reduction/withdrawal.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Rituximab, an anti-CD20 monoclonal antibody, has been shown to be as effective as cyclophosphamide to induce GPA and MPA remission, with an acceptable safety profile, leading to its registration by the FDA and EMA as remission-induction therapy in these patients.

In addition, the MAINRITSAN trial has demonstrated that 500 mg rituximab given every 6 months for 18 months was significantly more effective than azathioprine standard of care to maintain remission in patients with GPA or MPA, with a similar profile of tolerance.

EGPA patients were excluded from these trials. Long-term studies have shown that only 29% of EGPA patients achieved long-term remission and that relapses occurred in more than 40% of them, leading to high cumulative morbidity and damage. Moreover, most patients cannot be weaned off corticosteroids due to asthma and rhino-sinusal manifestations, even after vasculitis remission.

However, recent retrospective series indicated that rituximab may also be an effective remission induction and maintenance agent in refractory or relapsing EGPA. REOVAS, the first randomized controlled trial with rituximab as induction therapy in EGPA, has started within the French Vasculitis Study Group network.

The MAINRITSEG trial is a phase III, comparative, multicenter, randomized, double-blind, double-dummy and superiority trial, comparing pre-emptive low-dose rituximab-based regimen with azathioprine standard therapy, for the remission maintenance in newly-diagnosed or relapsing EGPA.

Patients, with newly diagnosed or relapsing EGPA, after achievement of remission, will be randomized in a 1:1 ratio to receive:

  • Standard regimen: maintenance oral azathioprine (2 mg/kg/day) for 24 months. This control group will receive conventional therapy plus 4 infusions of placebo-rituximab (every 6 months for 18 months)
  • Experimental regimen: pre-emptive 500-mg fixed-dose of rituximab every 6 months for 18 months (4 infusions). This group will receive intravenous rituximab plus orally placebo-azathioprine for 24 months.

All patients will receive standard of care therapy including glucocorticoid therapy reduction/withdrawal.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
98

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • France
    • Paris
      • Paris, Paris, France, 75014
        • Hôpital 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • patients with a diagnosis of EGPA according to Lanham and/or ACR 1990 criteria and/or Revised Chapel Hill Nomenclature and/or MIRRA study inclusion criteria
  • 18 years of age or more
  • with newly-diagnosed EGPA or after a vasculitis flare and remission achieved within the past year
  • independently of ANCA status
  • within 30-360 days following achievement of vasculitis remission (corresponding to a Birmingham Vasculitis Activity Score (BVAS)=0) achieved with an induction regimen including the one used in the REOVAS trial: either CS alone or in association with CYC (total dose ranging from 4.5-10 g for patients <65 years old and from 3-10g for patients ≥65 years old) or RTX (2 x 1g (D1, D15) or 4 weekly 375 mg/m2).
  • with a stable prednisone dose for 30 days or no more prednisone
  • after oral immunosuppressive drug cessation if started at remission.
  • Patients included in the REOVAS trial and achieving remission can be included at month 12 visit if they fulfil the other criteria
  • Patients able to give written informed consent prior to participation in the study.
  • Affiliation with a mode of social security (profit or being entitled).

Exclusion Criteria:

  • patients with GPA, MPA or other vasculitides
  • patients with vasculitis not in remission defined as a BVAS >0
  • acute or chronic active infections (including HIV, HBV or HCV)
  • active or recent cancer ( <5 years), except basocellular carcinoma and low activity prostatic cancer controlled by hormonal treatment
  • severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
  • pregnant women and lactation
  • patients with childbearing potential will have reliable contraception for all the duration of the study and another 12 months after. Women are considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient
  • men who refuse to use effective method of contraception (condom) from the date of consent through the end of the study
  • patients who had already been treated with rituximab before the last relapse/flare
  • patients who have been treated with rituximab with a different induction regimen than 2 x 1g (D1, D14) or 4 weekly 375 mg/m2 infusions
  • hypersensitivity to a monoclonal antibody or biologics
  • contraindication to rituximab or azathioprine
  • other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric diseases, that could interfere with participation
  • patients included in other investigational therapeutic study within the previous 3 months except in the REOVAS trial, after which patients achieving remission can be included if they fulfil the other criteria
  • patients suspected not to be observant to the proposed treatments
  • white blood cell count ≤4,000/mm3
  • platelet count ≤100,000/mm3
  • ALT or AST level >3 times the upper limit of normal
  • patients not able to stop allopurinol and febuxostat which may enhance azathioprine toxicity
  • patients unable to give written informed consent prior to participation in the study.

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: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Rituximab
  • pre-emptive 500-mg fixed-dose of IV rituximab every 6 months (total duration of 18 months = 4 infusions)
  • plus orally placebo-azathioprine for 24 months
Drug: Rituximab
pre-emptive 500-mg fixed-dose of IV rituximab every 6 months (total duration of 18 months = 4 infusions)
Drug: Placebo-azathioprine
oral tablets for 24 months
Active Comparator: Azathioprine
  • standard maintenance oral azathioprine therapy (2 mg/kg/day) for 24 months
  • plus 4 placebo-rituximab infusions given every 6 months for 18 months
Drug: Azathioprine
oral tablets : 2 mg/kg/day for 24 months
Drug: Placebo-rituximab
4 infusions for 18 months

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Duration of remission in weeks
Time Frame: 28 months
accrued number of weeks where a patient remains in remission with BVAS=0 and prednisone dose ≤7.5 mg/day
28 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
proportion of patients remaining in remission with a BVAS=0 and prednisone dose ≤7.5 mg/day
Time Frame: 28 months
28 months
proportion of patients with at least one vasculitis relapse (major, minor, either)
Time Frame: 28 months
28 months
proportion of patients with at least one clinically significant asthma/rhino-sinusal exacerbation
Time Frame: 28 months
defined as a worsening of asthma/rhino-sinusal disease leading to the doubling (or more) of the existing maintenance dose of corticosteroids for 3 or more days or hospital admission or an emergency department visit.
28 months
time to first vasculitis relapse
Time Frame: 28 months
28 months
time to first clinically significant asthma/rhino-sinusal exacerbation
Time Frame: 28 months
defined as a worsening of asthma/rhino-sinusal disease leading to the doubling (or more) of the existing maintenance dose of corticosteroids for 3 or more days or hospital admission or an emergency department visit.
28 months
variation of the obstructive pulmonary disease
Time Frame: 28 months
assessed by change of FEV1 at pulmonary function tests after use of a bronchodilator
28 months
prednisone dose at months 6, 12, 18, 24 and 28, and area under the curve over the 28 month study period
Time Frame: 28 months
28 months
proportion of patients with adverse events
Time Frame: 28 months
28 months
proportion of patients with serious adverse events
Time Frame: 28 months
28 months
proportion of patients with selected severe adverse events including grade 3 or 4 adverse effects (Common Terminology Criteria for Adverse Events)
Time Frame: 28 months
necessitating hospitalization, all cause deaths, cancers or infusion reactions (within 24 hours of infusion) that contraindicated further infusions
28 months
number and causes of deaths over the 28 month study period
Time Frame: 28 months
28 months
damage assessed by the mean variation of the Vasculitis Damage Index (VDI)
Time Frame: 28 months
28 months
quality of life assessed by the mean variation of the SF-36
Time Frame: 28 months
28 months
disability assessed by the mean variation of the Health Assessment Questionnaire (HAQ)
Time Frame: 28 months
28 months
number of days of hospitalization
Time Frame: 28 months
28 months
Accrued number of weeks where a patient remains in remission with BVAS=0 and prednisone dose ≤4 mg/day
Time Frame: 28 months
28 months
proportion of patients remaining in remission with a BVAS=0 over the 28 months study period
Time Frame: 28 months
28 months
proportion of participants who achieved remission of vasculitis (BVAS = 0) while receiving prednisone at a dose of 4.0 mg or less per day at month 6
Time Frame: 6 months
6 months
proportion of participants who achieved remission of vasculitis (BVAS = 0) while receiving prednisone at a dose of 4.0 mg or less per day at month 12
Time Frame: 12 months
12 months
proportion of participants who achieved remission of vasculitis (BVAS = 0) while receiving prednisone at a dose of 4.0 mg or less per day at month 18
Time Frame: 18 months
18 months
proportion of participants who achieved remission of vasculitis (BVAS = 0) while receiving prednisone at a dose of 4.0 mg or less per day at month 28
Time Frame: 28 months
28 months

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
URC-CIC Paris Descartes Necker Cochin
French Vasculitis Study Group

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Benjamin Terrier, National Referral Center for Rare Systemic Autoimmune Diseases - Hôpital Cochin

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 7, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 23, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 23, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 22, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 22, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 23, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 20, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 17, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P150922
  • 2016-000627-53 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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.

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