Association Corticosteroid/Azathioprine in Microscopic Polyangiitis/ Polyarteritis NODOSA or Churg Strauss Syndrome (CHUSPAN2)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00647166
First received: March 26, 2008
Last updated: January 2, 2014
Last verified: January 2014
  Purpose

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 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 Intervention Phase
MPA
FFS=0
At Diagnosis or Within the First 15 Days Following
Initiation of Corticosteroids.
Drug: corticosteroid and azathioprine
Drug: corticosteroid and placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Evaluation of a New Treatment Strategy for Patients With Microscopic Polyangiitis, Polyarteritis NODOSA or Churg Strauss Syndrome Without Poor Prognosis Factors

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • combined rate of remission treatment failure and relapse at 24 months [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

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

Enrollment: 114
Study Start Date: May 2008
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Name: corticosteroid and azathioprine
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
Other Name: corticosteroid and placebo

Detailed Description:

Patients with new diagnosis of 1) microscopic polyangiitis, polyarteritis NODOSA or Churg Strauss syndrome, and 2) with no 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-blind 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 achieved sustained remission and who did 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 relapse can be estimated at 40% at 24 months. The primary hypothesis of the CHUSPAN 2 is a reduction of 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • male or female patients
  • aged over 18 years
  • new diagnosis of microscopic polyangiitis, polyarteritis NODOSA or 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
  • physical examination

Exclusion Criteria:

  • patients with microscopic polyangiitis, polyarteritis NODOSA or 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 receiving immunosuppressant
  • relapse of 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 therapeutic trial
  • no affiliation to any of the general French health care system
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00647166

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:
No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00647166     History of Changes
Other Study ID Numbers: P 060243
Study First Received: March 26, 2008
Last Updated: January 2, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Vasculitis
Polyarteritis NODOSA (PAN)
Microscopic polyangiitis (MPA)
Churg Strauss syndrome (CSS)
Azathioprine

Additional relevant MeSH terms:
Churg-Strauss Syndrome
Microscopic Polyangiitis
Polyarteritis Nodosa
Syndrome
Systemic Vasculitis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Arteritis
Autoimmune Diseases
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Disease
Granuloma
Immune System Diseases
Lymphatic Diseases
Lymphoproliferative Disorders
Nervous System Diseases
Pathologic Processes
Skin Diseases
Skin Diseases, Vascular
Vascular Diseases
Vasculitis
Azathioprine
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors

ClinicalTrials.gov processed this record on October 21, 2014