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

At Diagnosis or Within the First 15 Days Following Initiation of Corticosteroids Clinical Trial

— CHUSPAN2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00647166
• Other study ID #: P 060243
• Status: Completed
• Phase: Phase 3
• First received: March 26, 2008
• Last updated: October 6, 2015
• Start date: May 2008
• Est. completion date: April 2015

Study information

• Verified date: October 2015
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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%.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: April 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• At Diagnosis or Within the First 15 Days Following Initiation of Corticosteroids
• Churg-Strauss Syndrome
• Microscopic Polyangiitis
• MPA
• PAN or EGPA With FFS=0
• Polyarteritis Nodosa
• Systemic Vasculitis
• Wegener Granulomatosis

Intervention

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
• 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

Locations

Country	Name	City	State
France	Hopital Cochin Pôle de Médecine UF Médecine Interne	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	combined rate of remission-treatment failures and minor or major relapses at 24 months		24 months	Yes
Secondary	initial remission rate (independently of subsequent relapse)		24 months	Yes
Secondary	number of patients who have a minor or major relapse		24 months	Yes
Secondary	number of serious treatment-related adverse effects		24 months	Yes
Secondary	number of patients with at least one treatment-related adverse effect		24 months	Yes
Secondary	severity of treatment-related effects according to the WHO toxicity grading system (grades 1 to 4; grades 3 and 4 for the severity)		24 months	Yes
Secondary	number of deaths and causes		24 months	Yes
Secondary	number of patients who could not be weaned of corticosteroids and dose required		24 months	Yes
Secondary	area under the curve for corticosteroids		24 months	Yes
Secondary	different scales, such as BVAS (activity of the disease), VDI (damage), HAQ, SF36, ADL and the evaluation of the need for health care facilities.		24 months	Yes
Secondary	number of flares with or without asthma and/or eosinophilia (only for EGPA analysis)		24 months	Yes