WEGENT - Comparison of Methotrexate or Azathioprine as Maintenance Therapy for ANCA-Associated Vasculitides

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.

Verified October 2007 by Hospices Civils de Lyon.
Recruitment status was: Active, not recruiting

Sponsor:

Information provided by:

Hospices Civils de Lyon

ClinicalTrials.gov Identifier:

NCT00349674

First received: July 6, 2006

Last updated: October 9, 2007

Last verified: October 2007

History of Changes

Purpose

Remission of ANCA-associated vasculitis can be obtained in approximately 80% of the patients with a combination of corticosteroids and cyclophosphamide. However, relapses are frequent. This point warrants the prescription of a maintenance treatment with a less toxic immunosuppressant for several months to years. The optimal drug in this indication is not determine. We decided therefore to compare the 2 most used drugs in this indication. Induction therapy consists in the combination of corticosteroids and intravenous cyclophosphamide pulses. Corticotherapy consisted first in one daily methylprednisolone pulse, for 1 to 3 days, followed by oral prednisolone at the dose of 1 mg/kg/d for 3 weeks, then progressively tapered and stopped at the 18th month from the diagnosis. Cyclophosphamide is administered every 2 weeks for the first 3 bolus (0.6 g/m2 - D1, 15 and 30), then every 3 weeks (0.7 g/m2). Once remission is achieved, patients receive 3 additional bolus (0.7 g/m2). At that time, patients are randomized for a maintenance treatment with azathioprine (2 mg/kg/d, orally) or oral methotrexate (starting at the dose of 0.3 mg/kg/wk, then progressively increased every weeks by 2.5mg, if necessary, to a maximum and optimal dose of 25 mg/wk) for 12 months.

Condition	Intervention	Phase
Systemic Wegener's Granulomatosis	Drug: Azathioprine: 2 mg/kg/day Drug: methotrexate 0.3 mg/kg/week, to a maximum and optimal dose of 25 mg/week	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label
Official Title:	Treatment of ANCA-Associated Vasculitides : Corticosteroids and Pulse Cyclophosphamide Followed by Maintenance Therapy With Methotrexate or Azathioprine: a Prospective Multicenter Randomized Trial

Resource links provided by NLM:

Genetics Home Reference related topics: granulomatosis with polyangiitis

MedlinePlus related topics: Vasculitis

Drug Information available for: Methotrexate Azathioprine Methotrexate sodium Azathioprine Sodium

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

U.S. FDA Resources

Further study details as provided by Hospices Civils de Lyon:

Primary Outcome Measures:

Safety/Efficacy
Frequency of severe adverse events in each arm. Hypothesis based upon NIH data was a rate of 6% severe adverse event with methotrexate compared to 30% with azathioprine (24% in one study on RA and 46% in one study on Sjögren syndrome).
Evaluation was planned after the last included patient has completed the assigned trial regimen (after 12 months of maintenance regimen or because of drug withdrawal).

Secondary Outcome Measures:

Relapse-free survival rate.
Cumulative event-free survival rate (adverse event- and relapse-free survival rate).
Health quality assessment using HAQ and SF36.
Efficacy of induction therapy with pulsed cyclophosphamide.
Second evaluation of the same outcome parameters is planned 5 years after the last included patient has completed the assigned trial regimen.


Estimated Enrollment:	126
Study Start Date:	January 1999

Eligibility


Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients aged over 18 years-old with newly diagnosed systemic Wegener's granulomatosis,
microscopic polyangitis with at least one factor of poor prognosis according to the five factors score (proteinuria > 1 g/day, renal insufficiency defined as a serum creatininemia > 140 µmol/L, specific cardiomyopathy, gastrointestinal tract and/or CNS involvement).

Exclusion Criteria:

MPA patients with no poor prognosis factor;
localized WG;
relapse of previously known WG or MPA;
treatment with corticosteroids for more than 1 month prior to diagnosis and start of immunosuppressant;
co-existence of another multi-system autoimmune disease;
malignancy (unless considered in complete remission and with no therapy for at least 3 years);
contra-indication to corticosteroids or study immunosuppressants; pregnancy or no use of contraception in non-menopaused women;
infection with human immunodeficiency virus; mental or physical disturbances not permitting to give consent.

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00349674

Locations


France
Christian PAGNOUX
Paris, France, 75

Sponsors and Collaborators

Hospices Civils de Lyon

Investigators


Principal Investigator:	Jean-François CORDIER, MD	Hospices Civils de Lyon

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Pagnoux C, Mahr A, Hamidou MA, Boffa JJ, Ruivard M, Ducroix JP, Kyndt X, Lifermann F, Papo T, Lambert M, Le Noach J, Khellaf M, Merrien D, Puéchal X, Vinzio S, Cohen P, Mouthon L, Cordier JF, Guillevin L; French Vasculitis Study Group. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med. 2008 Dec 25;359(26):2790-803. doi: 10.1056/NEJMoa0802311.


ClinicalTrials.gov Identifier:	NCT00349674 History of Changes
Other Study ID Numbers:	97.129
Study First Received:	July 6, 2006
Last Updated:	October 9, 2007

Keywords provided by Hospices Civils de Lyon:


Wegener's granulomatosis, microscopic polyangiitis, ANCA-associated vasculitis, methotrexate, azathioprine

Additional relevant MeSH terms:


Vasculitis Granulomatosis with Polyangiitis Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Vascular Diseases Cardiovascular Diseases Lung Diseases, Interstitial Lung Diseases Respiratory Tract Diseases Systemic Vasculitis Autoimmune Diseases Immune System Diseases Methotrexate Azathioprine Abortifacient Agents, Nonsteroidal	Abortifacient Agents Reproductive Control Agents Physiological Effects of Drugs Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunosuppressive Agents Immunologic Factors Antirheumatic Agents Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on June 23, 2017

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