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

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 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%.

Condition	Intervention	Phase
MPA PAN or EGPA With 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 Eosinophilic Granulomatosis With Polyangiitis (Churg Strauss Syndrome) Without Poor Prognosis Factors

Resource links provided by NLM:

Genetics Home Reference related topics: granulomatosis with polyangiitis pulmonary alveolar microlithiasis

MedlinePlus related topics: Granulomatosis with Polyangiitis Steroids Vasculitis

Drug Information available for: Azathioprine Azathioprine Sodium

Genetic and Rare Diseases Information Center resources: Granulomatosis With Polyangiitis Eosinophilic Granulomatosis With Polyangiitis Microscopic Polyangiitis Polyarteritis Nodosa Periarteritis Nodosa ANCA-associated Vasculitis

U.S. FDA Resources

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

Primary Outcome Measures:

combined rate of remission-treatment failures and minor or major relapses 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 ]
number of patients who have a minor or major relapse [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
number of serious treatment-related adverse effects [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
number of patients with at least one treatment-related adverse effect [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
number of deaths and causes [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
number of patients who could not be weaned of corticosteroids and dose required [ 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 ]
number of flares with or without asthma and/or eosinophilia (only for EGPA analysis) [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]


Enrollment:	114
Study Start Date:	May 2008
Study Completion Date:	April 2015
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
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

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
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 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

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


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:	October 6, 2015
Health Authority:	France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:


Vasculitis Polyarteritis nodosa (PAN) Microscopic polyangiitis (MPA)	Eosinophilic granulomatosis with polyangiitis (EGPA) Churg Strauss syndrome (CSS) Azathioprine

Additional relevant MeSH terms:


Syndrome Microscopic Polyangiitis Granulomatosis with Polyangiitis Polyarteritis Nodosa Churg-Strauss Syndrome Systemic Vasculitis Disease Pathologic Processes Cerebral Small Vessel Diseases Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Vascular Diseases Cardiovascular Diseases	Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Vasculitis Autoimmune Diseases Immune System Diseases Lung Diseases, Interstitial Lung Diseases Respiratory Tract Diseases Arteritis Skin Diseases, Vascular Skin Diseases Granuloma Lymphoproliferative Disorders Lymphatic Diseases Azathioprine Antimetabolites

ClinicalTrials.gov processed this record on September 29, 2016

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