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

Assistance Publique - Hôpitaux de Paris

Status and phase

Completed

Phase 3

Conditions

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

PAN or EGPA With FFS=0

MPA

Treatments

Drug: corticosteroid and placebo

Drug: corticosteroid and azathioprine

Study type

Interventional

Funder types

Other

Identifiers

NCT00647166

P 060243

Details and patient eligibility

About

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%.

Full 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.

Enrollment

114 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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