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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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,

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03290456
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

N/A
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Hospices Civils de Lyon
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Jean-Christophe LEGA, Pr
Principal Investigator Affiliation Hospices Civils de Lyon
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries France
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Granulomatosis With Polyangitis
Additional Details

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.

Arms & Interventions

Arms

Experimental: Prednisone 5mg/day extended of 12 additional months

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

Placebo Comparator: Placebo 5mg/day extended of 12 additional months

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

Interventions

Drug: - Prednisone 5mg/day extended of 12 additional months

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

Drug: - Placebo 5mg/day extended of 12 additionnal months.

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

CHU Amiens-Hôpital Nord, Amiens, France

Status

Recruiting

Address

CHU Amiens-Hôpital Nord

Amiens, , 80054

Site Contact

Jean SCHMIDT, MD

jean.schmidt@chu-amiens.fr

3 22 66 82 30 #+33

CHU Angers, Angers, France

Status

Recruiting

Address

CHU Angers

Angers, , 49933

Site Contact

Christian LAVIGNE, MD

chlavigne@chu-angers.fr

2 41 35 38 24 #+33

Clinique Rhône-Durance, Avignon, France

Status

Not yet recruiting

Address

Clinique Rhône-Durance

Avignon, , 84000

Site Contact

Pierre GOBERT, MD

pgobert@ch-avignon.fr

4 32 75 30 59 #+33

Hôpital Jeanne d'Arc, Bar-le-Duc, France

Status

Not yet recruiting

Address

Hôpital Jeanne d'Arc

Bar-le-Duc, , 55000

Site Contact

Philippe EVON, MD

pevon@pssm.fr

3.29.45.88.03 #+33

Hôpital Avicenne, Bobigny, France

Status

Not yet recruiting

Address

Hôpital Avicenne

Bobigny, , 93009

Site Contact

Robin DHOTE, MD

robin.dhote@avc.aphp.fr

1 48 95 58 70 #+33

Hôpital La Cavale Blanche, Brest, France

Status

Recruiting

Address

Hôpital La Cavale Blanche

Brest, , 29200

Site Contact

Claire DE MOREUIL, MD

claire.demoreuil@chu-brest.fr

2.98.34.73.36 #+33

Hôpital Louis Pradel, Bron, France

Status

Recruiting

Address

Hôpital Louis Pradel

Bron, , 69500

Site Contact

Vincent COTTIN, Pr

vincent.cottin@chu-lyon.fr

4 72 35 70 72 #+33

CHU de Caen - Cote de Nacre, Caen, France

Status

Recruiting

Address

CHU de Caen - Cote de Nacre

Caen, , 14033

Site Contact

Nicolas MARTIN-SILVA, MD

martinsilva.n@chu-caen.fr

2 31 06 57 32 #+33

Hôpital Louis Pasteur, Chartres, France

Status

Not yet recruiting

Address

Hôpital Louis Pasteur

Chartres, , 28018

Site Contact

Richard DAMADE, MD

rdamade@ch-chartres.fr

2 37 30 30 30 #+33

CHU Estaing, Clermont-Ferrand, France

Status

Recruiting

Address

CHU Estaing

Clermont-Ferrand, , 63003

Site Contact

Marc RUIVARD, Pr

mruivard@chu-clermontferrand.fr

4 73 75 00 85 #+33

CHU Gabriel Montpied, Clermont-Ferrand, France

Status

Recruiting

Address

CHU Gabriel Montpied

Clermont-Ferrand, , 63003

Site Contact

Olivier AUMAITRE, Pr

oaumaitre@chu-clermontferrand.fr

4 73 75 14 35 #+33

CHIC Créteil, Créteil, France

Status

Not yet recruiting

Address

CHIC Créteil

Créteil, , 94010

Site Contact

Antoine FROISSART, MD

antoine.froissart@chicreteil.fr

1 45 17 54 80 #+33

CHRU François Mitterrand, Dijon, France

Status

Not yet recruiting

Address

CHRU François Mitterrand

Dijon, , 21000

Site Contact

Bernard BONNOTTE, Pr

bernard.bonnotte@chu-dijon.fr

3 80 29 34 32 #+33

CHRU François Mitterrand, Dijon, France

Status

Not yet recruiting

Address

CHRU François Mitterrand

Dijon, , 21000

Site Contact

Jean-Michel REBIBOU, Pr

Jean-michel.rebibou@chu-dijon.fr

3 80 29 34 34 #+33

CHRU Lille - Hôpital Claude Huriez, Lille, France

Status

Not yet recruiting

Address

CHRU Lille - Hôpital Claude Huriez

Lille, , 59037

Site Contact

Eric HACHULLA, Pr

e-hachulla@chru-lille.fr

3 20 44 92 96 #+33

Centre Hospitalier Croix Rousse, Lyon, France

Status

Recruiting

Address

Centre Hospitalier Croix Rousse

Lyon, , 69004

Site Contact

Pascal SEVE, Pr

pascal.seve@chu-lyon.fr

4 26 73 26 36 #+33

Hôpital Edouard Herriot, Lyon, France

Status

Recruiting

Address

Hôpital Edouard Herriot

Lyon, , 69137

Site Contact

Arnaud HOT, Pr

arnaud.hot@chu-lyon.fr

4 72 11 75 68 #+33

Hôpital Edouard Herriot, Lyon, France

Status

Not yet recruiting

Address

Hôpital Edouard Herriot

Lyon, , 69137

Site Contact

Laurent JULLIARD, Pr

laurent.juillard@chu-lyon.fr

4 72 11 02 51 #+33

Hôpital de la Conception, Marseille, France

Status

Not yet recruiting

Address

Hôpital de la Conception

Marseille, , 13005

Site Contact

Gilles KAPLANSKI, Pr

Gilles.kaplanski@ap-hm.fr

4 91 38 35 01 #+33

Hôpital de la Conception, Marseille, France

Status

Not yet recruiting

Address

Hôpital de la Conception

Marseille, , 13005

Site Contact

Noémie JOURDE CHICHE, Pr

Noemie.jourde@ap-hm.fr

4 91 38 30 42 #+33

Hôpital La Timone, Marseille, France

Status

Not yet recruiting

Address

Hôpital La Timone

Marseille, , 13385

Site Contact

Nicolas SCHLEINITZ, Pr

nicolas.schleinitz@ap-hm.fr

4 91 38 87 62 #+33

HP Site Belle Isle, Metz, France

Status

Not yet recruiting

Address

HP Site Belle Isle

Metz, , 57045

Site Contact

François MAURIER, MD

francois.maurier@hp-metz.fr

3 57 84 15 01 #+33

CHU Nantes - Hôtel Dieu, Nantes, France

Status

Recruiting

Address

CHU Nantes - Hôtel Dieu

Nantes, , 44093

Site Contact

Antoine NEEL, MD

antoine.neel@chu-nantes.fr

2 40 08 77 65 #+33

CHU de Nice - Hôpital Pasteur 2, Nice, France

Status

Recruiting

Address

CHU de Nice - Hôpital Pasteur 2

Nice, , 06001

Site Contact

Nathalie TIEULIE, MD

tieulie.n@chu-nice.fr

4 92 03 54 77 #+33

Hôpital la Pitié Salpêtrière, Paris, France

Status

Recruiting

Address

Hôpital la Pitié Salpêtrière

Paris, , 75013

Site Contact

Patrice CACOUB, Pr

patrice.cacoub@psl.aphp.fr

1 42 17 80 27 #+33

Hôpital Cochin, Paris, France

Status

Recruiting

Address

Hôpital Cochin

Paris, , 75014

Site Contact

Xavier PUECHAL, Pr

xavier.puechal@aphp.fr

1 58 41 29 71 #+33

Hôpital Européen G. Pompidou, Paris, France

Status

Not yet recruiting

Address

Hôpital Européen G. Pompidou

Paris, , 75015

Site Contact

Alexandre KARRAS, Pr

alexandre.karras@egp.aphp.fr

1 56 09 37 60 #+33

Hôpital Saint Louis, Paris, France

Status

Not yet recruiting

Address

Hôpital Saint Louis

Paris, , 75475

Site Contact

Alfred MAHR, Pr

alfred.mahr@sls.aphp.fr

1 42 49 97 80 #+33

Hôpital Haut Lévêque, Pessac, France

Status

Not yet recruiting

Address

Hôpital Haut Lévêque

Pessac, , 33600

Site Contact

Jean-François VIALLARD, Pr

jean-francois.viallard@chu-bordeaux.fr

5 57 65 64 83 #+33

Centre Hospitalier Lyon Sud, Pierre-Bénite, France

Status

Recruiting

Address

Centre Hospitalier Lyon Sud

Pierre-Bénite, , 69310

Site Contact

Jean-Christophe LEGA, Pr

jean-christophe.lega@chu-lyon.fr

04.78.86.19.79

CH Lyon Sud, Pierre-Bénite, France

Status

Recruiting

Address

CH Lyon Sud

Pierre-Bénite, , 69495

Site Contact

Mathilde NOUVIER, Pr

mathilde.nouvier@chu-lyon.fr

4 72 67 87 01 #+33

CH Lyon Sud, Pierre-Bénite, France

Status

Recruiting

Address

CH Lyon Sud

Pierre-Bénite, , 69495

Site Contact

Jean Christophe LEGA, Pr

jean-christophe.lega@chu-lyon.fr

4.78.86.19.79 #+33

CHU de Poitiers, Poitiers, France

Status

Not yet recruiting

Address

CHU de Poitiers

Poitiers, , 86021

Site Contact

Mathieu PUYADE, MD

mathieu.puyade@chu-poitiers.fr

5 49 44 32 76 #+33

CHRU Rennes - Hôpital Sud, Rennes, France

Status

Recruiting

Address

CHRU Rennes - Hôpital Sud

Rennes, , 35200

Site Contact

Thomas LE GALLOU, MD

Thomas.LE.GALLOU@chu-rennes.fr

2 99 26 71 28 #+33

Hôpital Charles Nicolle, Rouen, France

Status

Recruiting

Address

Hôpital Charles Nicolle

Rouen, , 76031

Site Contact

Ygal BENHAMOU, MD

ygal.benhamou@chu-rouen.fr

2 32 88 90 14 #+33

CHU Strasbourg, Strasbourg, France

Status

Not yet recruiting

Address

CHU Strasbourg

Strasbourg, , 67000

Site Contact

Vincent POINDRON, MD

vincent.poindron@chru-strasbourg.fr

3 69 55 05 21 #+33

CHRU Hautepierre, Strasbourg, France

Status

Not yet recruiting

Address

CHRU Hautepierre

Strasbourg, , 67098

Site Contact

Jacques-Eric GOTTENBERG, Pr

jacques-eric.gottenberg@chru-strasbourg.fr

3 88 12 79 54 #+33

Strasbourg, France

Status

Recruiting

Address

Hopitaux Universaitaire de Strasbourg Hopitaux

Strasbourg, ,

Site Contact

Thierry KRUMMEL, MD

Thierry.krummel@chru-strasbourg.fr

3 69 55 13 22 #+33

Hôpital Foch, Suresnes, France

Status

Not yet recruiting

Address

Hôpital Foch

Suresnes, , 92150

Site Contact

Mathieu GROH, MD

je.kahn@hopital-foch.org

1 46 25 24 16 #+33

CHRU Bretonneau, Tours, France

Status

Not yet recruiting

Address

CHRU Bretonneau

Tours, , 37044

Site Contact

Elisabeth DIOT, MD

elisabeth.diot@chu-tours.fr

2 47 47 98 19 #+33

CH de Troyes, Troyes, France

Status

Recruiting

Address

CH de Troyes

Troyes, , 10003

Site Contact

Pascale CHAUVEAU-JOUVE, MD

pascale.chauveau-jouve@ch-troyes.fr

3 25 49 49 49 #+33

CH Valenciennes, Valenciennes, France

Status

Recruiting

Address

CH Valenciennes

Valenciennes, , 59322

Site Contact

Thomas QUEMENEUR, MD

quemeneur-t@ch-valenciennes.fr

3 27 14 30 89 #+33

Hôpitaux de Brabois, Vandœuvre-lès-Nancy, France

Status

Not yet recruiting

Address

Hôpitaux de Brabois

Vandœuvre-lès-Nancy, , 54511

Site Contact

Rolland JAUSSAUD, MD

r.jaussaud@chru-nancy.fr

3 83 15 40 60 #+33

CH Bretagne Atlantique, Vannes, France

Status

Recruiting

Address

CH Bretagne Atlantique

Vannes, , 56017

CH de Verdun, Verdun, France

Status

Not yet recruiting

Address

CH de Verdun

Verdun, , 55100

Site Contact

Assetou DIARRASOUBA, MD

adiarrassouba@ch-verdun.fr

3 29 83 64 42 #+33