Association Corticosteroid/Azathioprine in Microscopic Polyangiitis/ Polyarteritis Nodosa or Eosinophilic Granulomatosis With Polyangiitis (Churg Strauss Syndrome) (CHUSPAN2)

• ClinicalTrials.gov Identifier: NCT00647166
• Recruitment Status: Completed
• First Posted: March 31, 2008
• Last Update Posted: October 7, 2015
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

Brief Summary:

To determine whether a combination of corticosteroids and azathioprine can achieve a higher remission rate and a lower subsequent relapse rate in patients with newly-diagnosed microscopic polyangiitis, polyarteritis nodosa or eosinophilic granulomatosis with polyangiitis (Churg Strauss syndrome) with no poor prognosis factor (FFS=0), and without significantly increasing the rate of adverse events, as compared to corticosteroids alone. The study hypothesis is a reduction of the absolute risk of treatment failure or relapse within the first 24 months following initiation of therapy of least 25%.

Condition or disease	Intervention/treatment	Phase
MPA; PAN or EGPA With FFS=0; At Diagnosis or Within the First 15 Days Following Initiation of Corticosteroids	Drug: corticosteroid and azathioprine; Drug: corticosteroid and placebo	Phase 3

Detailed Description:

Patients with new diagnosis of 1) microscopic polyangiitis, polyarteritis nodosa or eosinophilic granulomatosis with polyangiitis (Churg Strauss syndrome) and 2) without any factor of poor prognosis according to the French five factors score (FFS - including creatininemia >140µmol/l, proteinuria >1 g/24 h, specific gastro-intestinal involvement, specific cardiomyopathy, and CNS involvement) can be included at diagnosis or within the first 15 days following initiation of corticosteroids. Treatment is randomly assigned, centrally, and received in a double-blinded fashion. It consists in a combination of azathioprine (2 mg/kg/day) and corticosteroids (starting at 1 mg/kg/day for 3 weeks then progressively tapered over a mean of 50 weeks, varying according to patient's weight) or, for the control group, the same corticosteroid therapy plus placebo. Duration of azathioprine or placebo is 12 months, and patients are followed for 12 additional months, yielding in a total duration of the protocol of 24 months after entry for each patient. End point is the number of patients who achieve sustained remission and who do not suffer a relapse during the 24 months of the study protocol. Based on the results of the early CHUSPAN trial for similar patients treated with corticosteroids alone, the cumulative rate of failures and relapses can be estimated at 40% at 24 months. The primary hypothesis of the CHUSPAN 2 is a reduction by at least 25% for the rate of this combined parameter of remission-treatment failure and relapse at 24 months. Based on this hypothesis, using a bilateral test, with a significance level of 5%, a beta level of 80% and an estimated 5% of lost-of-follow-up, 104 patients must be included. Secondary end points include the initial remission rate (independently of subsequent relapses), rate of adverse events and their severity according to the WHO toxicity grading system, number of deaths, number of patients who could not be weaned of corticosteroids, area under the curve for corticosteroids, and different scales, such as BVAS (activity of the disease), VDI (damage), HAQ, SF36, ADL and the evaluation of the need for health care facilities.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 114 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Evaluation of a New Treatment Strategy for Patients With Microscopic Polyangiitis, Polyarteritis Nodosa or Eosinophilic Granulomatosis With Polyangiitis (Churg Strauss Syndrome) Without Poor Prognosis Factors
• Study Start Date: May 2008
• Actual Primary Completion Date: March 2015
• Actual Study Completion Date: April 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; Drug: corticosteroid and azathioprine	Drug: corticosteroid and azathioprine; Corticosteroid 1 mg/kg/day with a conventional decrease dose; Azathioprine : 2 mg/kg/day during one year in 2 to 3 times a day by oral route
Placebo Comparator: 2; Drug: corticosteroid and placebo	Drug: corticosteroid and placebo; Corticosteroid 1 mg/kg/day with a conventional decrease dose; Placebo : 2 mg/kg/day during one year in 2 to 3 times a day by oral route

Outcome Measures

Primary Outcome Measures :

1. combined rate of remission-treatment failures and minor or major relapses at 24 months [ Time Frame: 24 months ]

Secondary Outcome Measures :

1. initial remission rate (independently of subsequent relapse) [ Time Frame: 24 months ]
2. number of patients who have a minor or major relapse [ Time Frame: 24 months ]
3. number of serious treatment-related adverse effects [ Time Frame: 24 months ]
4. number of patients with at least one treatment-related adverse effect [ Time Frame: 24 months ]
5. severity of treatment-related effects according to the WHO toxicity grading system (grades 1 to 4; grades 3 and 4 for the severity) [ Time Frame: 24 months ]
6. number of deaths and causes [ Time Frame: 24 months ]
7. number of patients who could not be weaned of corticosteroids and dose required [ Time Frame: 24 months ]
8. area under the curve for corticosteroids [ Time Frame: 24 months ]
9. different scales, such as BVAS (activity of the disease), VDI (damage), HAQ, SF36, ADL and the evaluation of the need for health care facilities. [ Time Frame: 24 months ]
10. number of flares with or without asthma and/or eosinophilia (only for EGPA analysis) [ Time Frame: 24 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• male or female patients
• aged over 18 years
• new diagnosis of microscopic polyangiitis, polyarteritis nodosa or eosinophilic granulomatosis with polyangiitis (Churg Strauss syndrome), satisfying ACR 1990 and/or Chapel Hill Nomenclature criteria (positive biopsy is not mandatory providing those criteria are fulfilled)
• with no factor of poor prognosis according to the French five factors score (FFS=0)
• at diagnosis or within the first 21 days following initiation of corticosteroids
• signed information and consent form
• patients covered by Health Insurance
• having had a baseline physical examination

Exclusion Criteria:

• patients with microscopic polyangiitis, polyarteritis nodosa or eosinophilic granulomatosis with polyangiitis (Churg Strauss syndrome) with one or more factor(s) of poor prognosis according to the French five factors score (FFS ≥ 1)
• patients with polyarteritis nodosa with ANCA, not satisfying the criteria for microscopic polyangiitis
• patients with clinically overt alveolar hemorrhage or respiratory distress syndrome
• patient treated with corticosteroids for more than 15 days or already receiving another immunosuppressant
• relapsing vasculitis
• other vasculitis, especially secondary vasculitides
• vasculitis secondary or associated with a viral infection, such as hepatitis B or C virus, or HIV
• malignancy
• pregnancy and breast feeding,women of child-bearing age not willing or with contra-indication to receive contraception
• contra-indication to any of the study agents
• need to continue allopurinol for those patients taking allopurinol
• consent deny or inability to receive information and give consent
• participation in another concomitant therapeutic trial
• no affiliation to any of the general French health care system

Contacts and Locations

Locations

France

Hopital Cochin Pôle de Médecine UF Médecine Interne

Paris, France, 75014

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

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

More Information

Additional Information:

Website of the French Vasculitis Study Group 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Puéchal X, Pagnoux C, Baron G, Lifermann F, Geffray L, Quémeneur T, Saraux JL, Wislez M, Cottin V, Ruivard M, Limal N, Aouba A, Bonnotte B, Néel A, Agard C, Cohen P, Terrier B, Le Jeunne C, Mouthon L, Ravaud P, Guillevin L; French Vasculitis Study Group investigators. Non-severe eosinophilic granulomatosis with polyangiitis: long-term outcomes after remission-induction trial. Rheumatology (Oxford). 2019 May 5. pii: kez139. doi: 10.1093/rheumatology/kez139. [Epub ahead of print]

Puéchal X, Pagnoux C, Baron G, Quémeneur T, Néel A, Agard C, Lifermann F, Liozon E, Ruivard M, Godmer P, Limal N, Mékinian A, Papo T, Ruppert AM, Bourgarit A, Bienvenu B, Geffray L, Saraux JL, Diot E, Crestani B, Delbrel X, Sailler L, Cohen P, Le Guern V, Terrier B, Groh M, Le Jeunne C, Mouthon L, Ravaud P, Guillevin L; French Vasculitis Study Group. Adding Azathioprine to Remission-Induction Glucocorticoids for Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss), Microscopic Polyangiitis, or Polyarteritis Nodosa Without Poor Prognosis Factors: A Randomized, Controlled Trial. Arthritis Rheumatol. 2017 Nov;69(11):2175-2186. doi: 10.1002/art.40205. Epub 2017 Oct 15.

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT00647166 History of Changes
• Other Study ID Numbers: P 060243
• First Posted: March 31, 2008
• Last Update Posted: October 7, 2015
• Last Verified: October 2015

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Vasculitis; Polyarteritis nodosa (PAN); Microscopic polyangiitis (MPA); Eosinophilic granulomatosis with polyangiitis (EGPA); Churg Strauss syndrome (CSS); Azathioprine

Additional relevant MeSH terms:

Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Systemic Vasculitis; Churg-Strauss Syndrome; Polyarteritis Nodosa; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Autoimmune Diseases; Immune System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Granuloma; Lymphoproliferative Disorders; Lymphatic Diseases; Arteritis; Skin Diseases, Vascular; Skin Diseases; Azathioprine; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antineoplastic Agents