Evaluate the Remission MAINtenance Using Extended Administration of Prednisone in Systemic Anti-neutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis. (MAINEPSAN)

September 9, 2025 updated by: Hospices Civils de Lyon

A Prospective, Multicentric, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Remission MAINtenance Using Extended Administration of Prednisone in Systemic Anti-neutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis.

Immunosuppressive therapy of granulomatosis with polyangiitis (GPA, Wegener's) and microscopic polyangiitis (MPA) has transformed the outcome from death to a strong likelihood of disease control and temporary remission. However, most patients have recurrent relapses that lead to damage and require repeated treatment associated with long-term morbidity and death.

Rituximab has been shown to be as effective as cyclophosphamide to induce remission and maintenance of remission in severe GPA and MPA patients, with an acceptable safety profile . Although rituximab is becoming the standard of care for maintenance therapy in these patients, relapse still occurs and the optimal duration of prednisone therapy remains debated.

On the one hand, most US studies use early withdrawal (6-12 months) because of feared side effects. On the other hand, most European trials propose late withdrawal (>18 months) given a lower observed relapse rate on long-term low dose glucocorticoids treatment.

In a systematic review and meta-analysis, glucocorticoids regimen was the most significant variable explaining the variability between the proportions of ANCA-associated vasculitis patients with relapses. Nevertheless, it was an indirect estimation of treatment effect because of the absence of dedicated randomized trial. This meta-analysis concluded that combined longer-term (i.e. >12 months) use of low dose prednisone or nonzero glucocorticoids target is associated with a 20% reduction of relapse compared to early withdrawal (i.e. ≤12 months).

The relapse rate in patients with early glucocorticoids (10-12 months) withdrawal was provided in two studies and was of 37 and 34%, respectively. By contrast, the relapse rate in patients with late prednisone withdrawal (18-24 months) and receiving rituximab as maintenance treatment was 14% at 24 months in the MAINRITSAN trial. Of note, the decision to withdraw glucocorticoids after 18 months was left to physician's discretion in this study and two thirds of the nonsevere relapses occurred when patients were off prednisone.

The trial detailed here is the first prospective trial evaluating the length of glucocorticoid administration as remission adjunctive treatment for patients with GPA or MPA.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Immunosuppressive therapy of granulomatosis with polyangiitis (GPA, Wegener's) and microscopic polyangiitis (MPA) has transformed the outcome from death to a strong likelihood of disease control and temporary remission. However, most patients have recurrent relapses that lead to damage and require repeated treatment associated with long-term morbidity and death.

Rituximab has been shown to be as effective as cyclophosphamide to induce remission and maintenance of remission in severe GPA and MPA patients, with an acceptable safety profile. Although rituximab is becoming the standard of care for maintenance therapy in these patients, relapse still occurs and the optimal duration of prednisone therapy remains debated.

On the one hand, most US studies use early withdrawal (6-12 months) because of feared side effects. On the other hand, most European trials propose late withdrawal (>18 months) given a lower observed relapse rate on long-term low dose glucocorticoids treatment.

In a systematic review and meta-analysis, glucocorticoids regimen was the most significant variable explaining the variability between the proportions of ANCA-associated vasculitis patients with relapses. Nevertheless, it was an indirect estimation of treatment effect because of the absence of dedicated randomized trial. This meta-analysis concluded that combined longer-term (i.e. >12 months) use of low dose prednisone or nonzero glucocorticoids target is associated with a 20% reduction of relapse compared to early withdrawal (i.e. ≤12 months).

The relapse rate in patients with early glucocorticoids (10-12 months) withdrawal was provided in two studies and was of 37 and 34%, respectively. By contrast, the relapse rate in patients with late prednisone withdrawal (18-24 months) and receiving rituximab as maintenance treatment was 14% at 24 months in the MAINRITSAN trial. Of note, the decision to withdraw glucocorticoids after 18 months was left to physician's discretion in this study and two thirds of the nonsevere relapses occurred when patients were off prednisone.

The trial detailed here is the first prospective trial evaluating the length of glucocorticoid administration as remission adjunctive treatment for patients with GPA or MPA.

Study Type

Interventional

Enrollment (Estimated)

146

Phase

  • Not Applicable

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 Backup

Study Locations

  • France
      • Amiens, France, 80054
        • Recruiting
        • CHU Amiens-Hopital Nord
        • Contact:
        • Principal Investigator:
          • Jean SCHMIDT, MD
      • Angers, France, 49933
        • Recruiting
        • CHU Angers
        • Contact:
        • Principal Investigator:
          • Christian LAVIGNE, MD
      • Avignon, France, 84000
        • Not yet recruiting
        • Clinique Rhône-Durance
        • Contact:
        • Principal Investigator:
          • Pierre GOBERT, MD
      • Bar-le-Duc, France, 55000
        • Not yet recruiting
        • Hôpital Jeanne d'Arc
        • Contact:
          • Philippe EVON, MD
          • Phone Number: +33 3.29.45.88.03
          • Email: pevon@pssm.fr
        • Principal Investigator:
          • Philippe EVON, MD
      • Bobigny, France, 93009
        • Not yet recruiting
        • Hôpital Avicenne
        • Contact:
        • Principal Investigator:
          • Robin DHOTE, MD
      • Brest, France, 29200
        • Recruiting
        • Hôpital La Cavale Blanche
        • Contact:
        • Principal Investigator:
          • Claire DE MOREUIL, MD
      • Bron, France, 69500
        • Recruiting
        • Hôpital Louis Pradel
        • Contact:
        • Principal Investigator:
          • Vincent Cottin, Pr
      • Caen, France, 14033
        • Recruiting
        • CHU de Caen - Côte de Nacre
        • Contact:
        • Principal Investigator:
          • Nicolas MARTIN-SILVA, MD
      • Chartres, France, 28018
        • Not yet recruiting
        • Hopital Louis Pasteur
        • Contact:
        • Principal Investigator:
          • Richard DAMADE, MD
      • Clermont-Ferrand, France, 63003
        • Recruiting
        • Chu Estaing
        • Contact:
        • Principal Investigator:
          • Marc RUIVARD, Pr
      • Clermont-Ferrand, France, 63003
        • Recruiting
        • CHU Gabriel Montpied
        • Contact:
        • Principal Investigator:
          • Olivier AUMAITRE, Pr
      • Créteil, France, 94010
        • Not yet recruiting
        • CHIC Créteil
        • Contact:
        • Principal Investigator:
          • Antoine FROISSART, MD
      • Dijon, France, 21000
        • Not yet recruiting
        • CHRU François Mitterrand
        • Contact:
        • Principal Investigator:
          • Jean-Michel REBIBOU, Pr
      • Lille, France, 59037
        • Not yet recruiting
        • CHRU Lille - Hôpital Claude Huriez
        • Contact:
        • Principal Investigator:
          • Eric HACHULLA, Pr
      • Lyon, France, 69004
        • Recruiting
        • Centre Hospitalier Croix Rousse
        • Contact:
        • Principal Investigator:
          • Pascal SEVE, Pr
      • Lyon, France, 69137
        • Recruiting
        • Hopital Edouard Herriot
        • Contact:
        • Principal Investigator:
          • Arnaud HOT, Pr
      • Lyon, France, 69137
        • Not yet recruiting
        • Hopital Edouard Herriot
        • Contact:
        • Principal Investigator:
          • Laurent JULLIARD, Pr
      • Marseille, France, 13005
        • Not yet recruiting
        • Hôpital de la Conception
        • Contact:
        • Principal Investigator:
          • Noémie JOURDE CHICHE, Pr
      • Marseille, France, 13385
        • Not yet recruiting
        • Hôpital La Timone
        • Contact:
        • Principal Investigator:
          • Nicolas SCHLEINITZ, Pr
      • Metz, France, 57045
        • Not yet recruiting
        • HP Site Belle Isle
        • Contact:
        • Principal Investigator:
          • François MAURIER, MD
      • Nantes, France, 44093
        • Recruiting
        • CHU NANTES - Hôtel Dieu
        • Principal Investigator:
          • Antoine NEEL, MD
        • Contact:
      • Nice, France, 06001
        • Recruiting
        • CHU de Nice - Hôpital Pasteur 2
        • Contact:
        • Principal Investigator:
          • Nathalie TIEULIE, MD
      • Paris, France, 75014
        • Recruiting
        • Hopital Cochin
        • Contact:
        • Principal Investigator:
          • Xavier PUECHAL, Pr
      • Paris, France, 75013
        • Recruiting
        • Hôpital La Pitié Salpêtrière
        • Contact:
        • Principal Investigator:
          • Patrice CACOUB, Pr
      • Paris, France, 75475
        • Not yet recruiting
        • Hopital Saint Louis
        • Contact:
        • Principal Investigator:
          • Alfred MAHR, Pr
      • Paris, France, 75015
        • Not yet recruiting
        • Hopital Europeen G. Pompidou
        • Contact:
        • Principal Investigator:
          • Alexandre KARRAS, Pr
      • Pessac, France, 33600
        • Not yet recruiting
        • Hopital Haut Leveque
        • Contact:
        • Principal Investigator:
          • Jean-François VIALLARD, Pr
      • Pierre-Bénite, France, 69310
      • Pierre-Bénite, France, 69495
        • Recruiting
        • CH Lyon Sud
        • Contact:
        • Principal Investigator:
          • Jean Christophe LEGA, Pr
      • Poitiers, France, 86021
        • Not yet recruiting
        • Chu de Poitiers
        • Contact:
        • Principal Investigator:
          • Mathieu PUYADE, MD
      • Rennes, France, 35200
        • Recruiting
        • CHRU Rennes - Hôpital Sud
        • Contact:
        • Principal Investigator:
          • Thomas LE GALLOU, MD
      • Rouen, France, 76031
        • Recruiting
        • Hopital Charles Nicolle
        • Contact:
        • Principal Investigator:
          • Ygal BENHAMOU, MD
      • Strasbourg, France, 67000
        • Not yet recruiting
        • CHU Strasbourg
        • Contact:
        • Principal Investigator:
          • Vincent POINDRON, MD
      • Strasbourg, France, 67098
      • Strasbourg, France
        • Recruiting
        • Hopitaux Universaitaire de Strasbourg Hopitaux
        • Contact:
        • Principal Investigator:
          • Thierry KRUMMEL, MD
      • Suresnes, France, 92150
        • Not yet recruiting
        • Hopital Foch
        • Contact:
        • Principal Investigator:
          • Mathieu GROH, MD
      • Tours, France, 37044
        • Not yet recruiting
        • CHRU Bretonneau
        • Contact:
        • Principal Investigator:
          • Elisabeth DIOT, MD
      • Troyes, France, 10003
        • Recruiting
        • CH de Troyes
        • Contact:
        • Principal Investigator:
          • Pascale CHAUVEAU-JOUVE, MD
      • Valenciennes, France, 59322
        • Recruiting
        • Ch Valenciennes
        • Contact:
        • Principal Investigator:
          • Thomas QUEMENEUR, MD
      • Vandœuvre-lès-Nancy, France, 54511
        • Not yet recruiting
        • Hopitaux de Brabois
        • Contact:
        • Principal Investigator:
          • Rolland JAUSSAUD, MD
      • Vannes, France, 56017
      • Verdun, France, 55100
        • Not yet recruiting
        • CH de Verdun
        • Contact:
        • Principal Investigator:
          • Assetou DIARRASOUBA, MD

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

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with a diagnosis of MPA or GPA independently of ANCA status,
  • Patient aged of 18 years or older,
  • Patients with newly-diagnosed disease or relapsing disease at the time of screening, with an inactive disease defined as a BVAS = 0,
  • Patients receiving maintenance infusion of rituximab 500 mg at 6 and 12 months after the start of vasculitis induction
  • Patients receiving 5-10 mg/day of prednisone at screening,
  • Patient able to give written informed consent prior to participation in the study.
  • At Inclusion visit day, patient must be between 5 and 10 mg/day prednisone and at randomization visit day (D1), patient must be at 5 mg/day prednisone

Exclusion Criteria:

  • Patients with EGPA, or other vasculitides, defined by the ACR criteria and/or the Chapel Hill Consensus Conference,
  • Patients with vasculitis with active disease defined as a BVAS >0,
  • Patients with acute infections or chronic active infections (including HIV, HBV or HCV),
  • Patients with active cancer or recent cancer (<5 years), except basocellular carcinoma and prostatic cancer of low activity controlled by hormonal treatment,
  • Pregnant women and lactation. Patients with childbearing potential should have reliable contraception for the all duration of the study,
  • Patients with other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric diseases, that could interfere with participation in the trial according to the protocol,
  • Patients included in other investigational therapeutic study within the previous 3 months,
  • Patients suspected not to be observant to the proposed treatments,
  • Patients who have white blood cell count ≤4,000/mm3,
  • Patients who have platelet count ≤100,000/mm3,
  • Patients who have ALT or AST level greater than 3 times the upper limit of normal that cannot be attributed to underlying MPA-GPA disease,
  • Patients unable to give written informed consent prior to participation in the study.
  • Patients with contraindication to use rituximab,

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Prednisone 5mg/day extended of 12 additional months
Prednisone 5mg/day will be administered from Day 1 to Month 12
Drug: Prednisone 5mg/day extended of 12 additional months
Prednisone 5mg/day orally during 12 Month + 1 mg/week tapering until 0mg.
Placebo Comparator: Placebo 5mg/day extended of 12 additional months
Placebo 5mg/day will be administered from Day 1 to Month 12
Drug: Placebo 5mg/day extended of 12 additionnal months.
1mg/week orally tapering Prednisone until Month 1 + Placebo orally 5mg/day until Month 13

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relapse-free survival, relapse being defined as BVAS > 0.
Time Frame: from Screening to Month 30.
rate of relapse-free survival of patients continuing low-dose prednisone treatment until Month 10 VS those who will have prednisone treatment cessation at Month 1, on remission maintenance with Rituximab therapy, after achievement of remission of GPA or MPA, defined as a survival of patients maintaining a BVAS=0 at Month 30, in patient with newly-diagnosed or relapsing GPA or MPA and who will all have received glucocorticoids for 12 months after diagnosis or last flare before inclusion.
from Screening to Month 30.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Compare the rate of serious adverse events between Inclusion and Month 30 after randomization
Time Frame: from Day 1 to Month 30

Proportion of patients with at least one adverse event between inclusion and Month 30.

  • Percentage of patients with at least one serious adverse event between inclusion and Month 30, corresponding to any adverse event that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity or congenital anomaly/birth defect or any other adverse event considered "medically significant".
  • Number of deaths, whatever the cause at Month 30.
from Day 1 to Month 30
Compare the rate of predefined severe events related to glucocorticoids between inclusion and Month 30 including osteoporotic fracture and weight gain.
Time Frame: From Screening to Month 30

Percentage of patients with at least one predefined severe event corresponding to adverse events of grade 3 to 5 of the Common Terminology Criteria, including severe side effect related to glucocorticoids (infection requiring hospitalization or intravenous antibiotics, osteoporotic fracture, diabetes requiring medication, cardiovascular event, symptomatic osteonecrosis, psychiatric or mood disorder requiring drug administration, weight gain >10 kg) between inclusion and Month 30

- Weight gain between inclusion and Month 30
From Screening to Month 30
To compare the rate of vasculitis relapse at Month 30
Time Frame: from Day 1 to Month 30
Proportion of patients with minor or major vasculitis relapse between inclusion and Month 30 (BVAS >0) and time to first vasculitis relapse
from Day 1 to Month 30
To compare the prednisone use between inclusion and Month 30
Time Frame: from screening to Month 30
Prednisone area under the curve of administrated dose between inclusion and Month 30
from screening to Month 30
To compare variation of the Bone mineral density and markers between inclusion and Month 30
Time Frame: From Screening to Month 30

Variation of the Bone mineral density between inclusion and Month 30

- Variation of the Bone markers including C-terminal crosslinked telopeptide of type I collagen (CTX) and serum procollagen type 1 amino-terminal propeptide (P1NP) between inclusion and Month 30
From Screening to Month 30
To compare sequelae assessed by BVAS (vasculitis activity) at 30 months
Time Frame: From Screening to Month 30.

BVAS (vasculitis activity) at 30 months

- Variation of BVAS (Vasculitis activity)
From Screening to Month 30.
To compare sequelae assessed by the Vasculitis Damage Index (VDI) at 30 months
Time Frame: From screening to Month 30.
  • Vasculitis Damage Index at 30 months
  • Variation of VDI,
From screening to Month 30.
- To compare sequelae assessed by Combined Damage Assessment Index (CDA) at 30 months
Time Frame: From Screening to Month 30.
  • Combined Damage Assessment Index at 30 months
  • Variation of CDA (damage),
From Screening to Month 30.
- To compare functional disability at Month 30 after randomization (Day 1) in both arms
Time Frame: From Day 1 to Month 30.
Variation of HAQ (disability) between inclusion and at Month 30
From Day 1 to Month 30.
To compare quality of life at Month 30 after randomization (Day 1) in both arms
Time Frame: - From Day 1 to Month 30.
- Variation of SF-36 (quality of life) between inclusion and at Month 30
- From Day 1 to Month 30.
- To compare healthcare resource utilization at Month 30 after randomization (Day 1) in both arms
Time Frame: From Day 1 to Month 30.
- Healthcare resource utilization between inclusion and Month 30 being defined as the percentage of patients being hospitalized at least once except only for rituximab infusions
From Day 1 to Month 30.

Collaborators and Investigators

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

Sponsor

Hospices Civils de Lyon

Investigators

  • Principal Investigator: Jean-Christophe LEGA, Pr, Hospices Civils de Lyon

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)

August 20, 2019

Primary Completion (Estimated)

October 20, 2029

Study Completion (Estimated)

October 20, 2029

Study Registration Dates

First Submitted

August 24, 2017

First Submitted That Met QC Criteria

September 19, 2017

First Posted (Actual)

September 25, 2017

Study Record Updates

Last Update Posted (Estimated)

September 15, 2025

Last Update Submitted That Met QC Criteria

September 9, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 69HCL17_0020

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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