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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00349674
Recruitment Status : Unknown
Verified October 2007 by Hospices Civils de Lyon.
Recruitment status was:  Active, not recruiting
First Posted : July 7, 2006
Last Update Posted : October 10, 2007
Information provided by:
Hospices Civils de Lyon

Brief Summary:
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 or disease Intervention/treatment 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  (Clinical Trial)
Enrollment : 126 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : January 1999

Primary Outcome Measures :
  1. Safety/Efficacy
  2. 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).
  3. 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 :
  1. Relapse-free survival rate.
  2. Cumulative event-free survival rate (adverse event- and relapse-free survival rate).
  3. Health quality assessment using HAQ and SF36.
  4. Efficacy of induction therapy with pulsed cyclophosphamide.
  5. Second evaluation of the same outcome parameters is planned 5 years after the last included patient has completed the assigned trial regimen.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00349674

Christian PAGNOUX
Paris, France, 75
Sponsors and Collaborators
Hospices Civils de Lyon
Principal Investigator: Jean-François CORDIER, MD Hospices Civils de Lyon

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00349674     History of Changes
Other Study ID Numbers: 97.129
First Posted: July 7, 2006    Key Record Dates
Last Update Posted: October 10, 2007
Last Verified: October 2007

Keywords provided by Hospices Civils de Lyon:
Wegener's granulomatosis,
microscopic polyangiitis,
ANCA-associated vasculitis,

Additional relevant MeSH terms:
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
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors