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

NCT ID: NCT03290456

Last Updated: 2025-09-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

146 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-20

Study Completion Date

2029-10-20

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Granulomatosis With Polyangitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Prednisone 5mg/day extended of 12 additional months

Prednisone 5mg/day will be administered from Day 1 to Month 12

Group Type EXPERIMENTAL

Prednisone 5mg/day extended of 12 additional months

Intervention Type DRUG

Prednisone 5mg/day orally during 12 Month + 1 mg/week tapering until 0mg.

Placebo 5mg/day extended of 12 additional months

Placebo 5mg/day will be administered from Day 1 to Month 12

Group Type PLACEBO_COMPARATOR

Placebo 5mg/day extended of 12 additionnal months.

Intervention Type DRUG

1mg/week orally tapering Prednisone until Month 1 + Placebo orally 5mg/day until Month 13

Interventions

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Prednisone 5mg/day extended of 12 additional months

Prednisone 5mg/day orally during 12 Month + 1 mg/week tapering until 0mg.

Intervention Type DRUG

Placebo 5mg/day extended of 12 additionnal months.

1mg/week orally tapering Prednisone until Month 1 + Placebo orally 5mg/day until Month 13

Intervention Type DRUG

Eligibility Criteria

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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,
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospices Civils de Lyon

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean-Christophe LEGA, Pr

Role: PRINCIPAL_INVESTIGATOR

Hospices Civils de Lyon

Locations

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CHU Amiens-Hôpital Nord

Amiens, , France

Site Status RECRUITING

CHU Angers

Angers, , France

Site Status RECRUITING

Clinique Rhône-Durance

Avignon, , France

Site Status NOT_YET_RECRUITING

Hôpital Jeanne d'Arc

Bar-le-Duc, , France

Site Status NOT_YET_RECRUITING

Hôpital Avicenne

Bobigny, , France

Site Status NOT_YET_RECRUITING

Hôpital La Cavale Blanche

Brest, , France

Site Status RECRUITING

Hôpital Louis Pradel

Bron, , France

Site Status RECRUITING

CHU de Caen - Cote de Nacre

Caen, , France

Site Status RECRUITING

Hôpital Louis Pasteur

Chartres, , France

Site Status NOT_YET_RECRUITING

CHU Estaing

Clermont-Ferrand, , France

Site Status RECRUITING

CHU Gabriel Montpied

Clermont-Ferrand, , France

Site Status RECRUITING

CHIC Créteil

Créteil, , France

Site Status NOT_YET_RECRUITING

CHRU François Mitterrand

Dijon, , France

Site Status NOT_YET_RECRUITING

CHRU François Mitterrand

Dijon, , France

Site Status NOT_YET_RECRUITING

CHRU Lille - Hôpital Claude Huriez

Lille, , France

Site Status NOT_YET_RECRUITING

Centre Hospitalier Croix Rousse

Lyon, , France

Site Status RECRUITING

Hôpital Edouard Herriot

Lyon, , France

Site Status RECRUITING

Hôpital Edouard Herriot

Lyon, , France

Site Status NOT_YET_RECRUITING

Hôpital de la Conception

Marseille, , France

Site Status NOT_YET_RECRUITING

Hôpital de la Conception

Marseille, , France

Site Status NOT_YET_RECRUITING

Hôpital La Timone

Marseille, , France

Site Status NOT_YET_RECRUITING

HP Site Belle Isle

Metz, , France

Site Status NOT_YET_RECRUITING

CHU Nantes - Hôtel Dieu

Nantes, , France

Site Status RECRUITING

CHU de Nice - Hôpital Pasteur 2

Nice, , France

Site Status RECRUITING

Hôpital la Pitié Salpêtrière

Paris, , France

Site Status RECRUITING

Hôpital Cochin

Paris, , France

Site Status RECRUITING

Hôpital Européen G. Pompidou

Paris, , France

Site Status NOT_YET_RECRUITING

Hôpital Saint Louis

Paris, , France

Site Status NOT_YET_RECRUITING

Hôpital Haut Lévêque

Pessac, , France

Site Status NOT_YET_RECRUITING

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status RECRUITING

CH Lyon Sud

Pierre-Bénite, , France

Site Status RECRUITING

CH Lyon Sud

Pierre-Bénite, , France

Site Status RECRUITING

CHU de Poitiers

Poitiers, , France

Site Status NOT_YET_RECRUITING

CHRU Rennes - Hôpital Sud

Rennes, , France

Site Status RECRUITING

Hôpital Charles Nicolle

Rouen, , France

Site Status RECRUITING

CHU Strasbourg

Strasbourg, , France

Site Status NOT_YET_RECRUITING

CHRU Hautepierre

Strasbourg, , France

Site Status NOT_YET_RECRUITING

Hopitaux Universaitaire de Strasbourg Hopitaux

Strasbourg, , France

Site Status RECRUITING

Hôpital Foch

Suresnes, , France

Site Status NOT_YET_RECRUITING

CHRU Bretonneau

Tours, , France

Site Status NOT_YET_RECRUITING

CH de Troyes

Troyes, , France

Site Status RECRUITING

CH Valenciennes

Valenciennes, , France

Site Status RECRUITING

Hôpitaux de Brabois

Vandœuvre-lès-Nancy, , France

Site Status NOT_YET_RECRUITING

CH Bretagne Atlantique

Vannes, , France

Site Status RECRUITING

CH de Verdun

Verdun, , France

Site Status NOT_YET_RECRUITING

Countries

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France

Central Contacts

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Jean-Christophe LEGA, Pr

Role: CONTACT

04.78.86.19.79

Xavier Puéchal, Dr

Role: CONTACT

01.58.41.32.41

Facility Contacts

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Jean SCHMIDT, MD

Role: primary

3 22 66 82 30 ext. +33

Christian LAVIGNE, MD

Role: primary

2 41 35 38 24 ext. +33

Pierre GOBERT, MD

Role: primary

4 32 75 30 59 ext. +33

Philippe EVON, MD

Role: primary

3.29.45.88.03 ext. +33

Robin DHOTE, MD

Role: primary

1 48 95 58 70 ext. +33

Claire DE MOREUIL, MD

Role: primary

2.98.34.73.36 ext. +33

Vincent COTTIN, Pr

Role: primary

4 72 35 70 72 ext. +33

Nicolas MARTIN-SILVA, MD

Role: primary

2 31 06 57 32 ext. +33

Richard DAMADE, MD

Role: primary

2 37 30 30 30 ext. +33

Marc RUIVARD, Pr

Role: primary

4 73 75 00 85 ext. +33

Olivier AUMAITRE, Pr

Role: primary

4 73 75 14 35 ext. +33

Antoine FROISSART, MD

Role: primary

1 45 17 54 80 ext. +33

Bernard BONNOTTE, Pr

Role: primary

3 80 29 34 32 ext. +33

Jean-Michel REBIBOU, Pr

Role: primary

3 80 29 34 34 ext. +33

Eric HACHULLA, Pr

Role: primary

3 20 44 92 96 ext. +33

Pascal SEVE, Pr

Role: primary

4 26 73 26 36 ext. +33

Arnaud HOT, Pr

Role: primary

4 72 11 75 68 ext. +33

Laurent JULLIARD, Pr

Role: primary

4 72 11 02 51 ext. +33

Gilles KAPLANSKI, Pr

Role: primary

4 91 38 35 01 ext. +33

Noémie JOURDE CHICHE, Pr

Role: primary

4 91 38 30 42 ext. +33

Nicolas SCHLEINITZ, Pr

Role: primary

4 91 38 87 62 ext. +33

François MAURIER, MD

Role: primary

3 57 84 15 01 ext. +33

Antoine NEEL, MD

Role: primary

2 40 08 77 65 ext. +33

Nathalie TIEULIE, MD

Role: primary

4 92 03 54 77 ext. +33

Patrice CACOUB, Pr

Role: primary

1 42 17 80 27 ext. +33

Xavier PUECHAL, Pr

Role: primary

1 58 41 29 71 ext. +33

Alexandre KARRAS, Pr

Role: primary

1 56 09 37 60 ext. +33

Alfred MAHR, Pr

Role: primary

1 42 49 97 80 ext. +33

Jean-François VIALLARD, Pr

Role: primary

5 57 65 64 83 ext. +33

Jean-Christophe LEGA, Pr

Role: primary

04.78.86.19.79

Mathilde NOUVIER, Pr

Role: primary

4 72 67 87 01 ext. +33

Jean Christophe LEGA, Pr

Role: primary

4.78.86.19.79 ext. +33

Mathieu PUYADE, MD

Role: primary

5 49 44 32 76 ext. +33

Thomas LE GALLOU, MD

Role: primary

2 99 26 71 28 ext. +33

Ygal BENHAMOU, MD

Role: primary

2 32 88 90 14 ext. +33

Vincent POINDRON, MD

Role: primary

3 69 55 05 21 ext. +33

Jacques-Eric GOTTENBERG, Pr

Role: primary

3 88 12 79 54 ext. +33

Thierry KRUMMEL, MD

Role: primary

3 69 55 13 22 ext. +33

Mathieu GROH, MD

Role: primary

1 46 25 24 16 ext. +33

Elisabeth DIOT, MD

Role: primary

2 47 47 98 19 ext. +33

Pascale CHAUVEAU-JOUVE, MD

Role: primary

3 25 49 49 49 ext. +33

Thomas QUEMENEUR, MD

Role: primary

3 27 14 30 89 ext. +33

Rolland JAUSSAUD, MD

Role: primary

3 83 15 40 60 ext. +33

Pascal GODMER, MD

Role: primary

2 97 01 41 45 ext. +33

Assetou DIARRASOUBA, MD

Role: primary

3 29 83 64 42 ext. +33

Other Identifiers

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69HCL17_0020

Identifier Type: -

Identifier Source: org_study_id

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