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

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

Tracking Information
First Submitted Date  ICMJE March 26, 2008
First Posted Date  ICMJE March 31, 2008
Last Update Posted Date October 7, 2015
Study Start Date  ICMJE May 2008
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 10, 2015)
combined rate of remission-treatment failures and minor or major relapses at 24 months [ Time Frame: 24 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 26, 2008)
combined rate of remission treatment failure and relapse at 24 months [ Time Frame: 24 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 10, 2015)
  • 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 Measures  ICMJE
 (submitted: March 26, 2008)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Association Corticosteroid/Azathioprine in Microscopic Polyangiitis/ Polyarteritis Nodosa or Eosinophilic Granulomatosis With Polyangiitis (Churg Strauss Syndrome)
Official Title  ICMJE 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
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 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • MPA
  • PAN or EGPA With FFS=0
  • At Diagnosis or Within the First 15 Days Following Initiation of Corticosteroids
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • Experimental: 1
    Drug: corticosteroid and azathioprine
    Intervention: Drug: corticosteroid and azathioprine
  • Placebo Comparator: 2
    Drug: corticosteroid and placebo
    Intervention: Drug: corticosteroid and placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 10, 2012)
114
Original Estimated Enrollment  ICMJE
 (submitted: March 26, 2008)
104
Actual Study Completion Date  ICMJE April 2015
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00647166
Other Study ID Numbers  ICMJE P 060243
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Loic Guillevin, MD, PhD French Vasculitis Study Group
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP