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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Evaluation of a New Treatment Strategy for Patients With Microscopic Polyangiitis, Polyarteritis Nodosa or Eosinophilic Granulomatosis With Polyangiitis (Churg Strauss Syn

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%.

Detailed Summary: 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, a
Sponsor: Assistance Publique - Hôpitaux de Paris

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

Original Primary Outcome: combined rate of remission treatment failure and relapse at 24 months [ Time Frame: 24 months ]

Current Secondary Outcome:

  • initial remission rate (independently of subsequent relapse) [ Time Frame: 24 months ]
  • number of patients who have a minor or major relapse [ Time Frame: 24 months ]
  • number of serious treatment-related adverse effects [ Time Frame: 24 months ]
  • number of patients with at least one treatment-related adverse effect [ Time Frame: 24 months ]
  • 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 ]
  • number of deaths and causes [ Time Frame: 24 months ]
  • number of patients who could not be weaned of corticosteroids and dose required [ Time Frame: 24 months ]
  • area under the curve for corticosteroids [ Time Frame: 24 months ]
  • 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 ]
  • number of flares with or without asthma and/or eosinophilia (only for EGPA analysis) [ Time Frame: 24 months ]


Original Secondary Outcome:

  • initial remission rate (independently of subsequent relapse) [ Time Frame: 24 months ]
  • rates of adverse events and their severity according to the WHO toxicity grading system [ Time Frame: 24 months ]
  • number of deaths [ Time Frame: 24 months ]
  • number of patients who could not be weaned of corticosteroids [ Time Frame: 24 months ]
  • area under the curve for corticosteroids [ Time Frame: 24 months ]
  • 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 ]


Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: March 26, 2008
Date Started: May 2008
Date Completion:
Last Updated: October 6, 2015
Last Verified: October 2015