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

The recruitment status of this study is unknown because the information has not been verified recently.
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
  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:


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
Genders Eligible for Study:   Both
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
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

Additional Information:
No publications provided by Hospices Civils de Lyon

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00349674     History of Changes
Other Study ID Numbers: 97.129
Study First Received: July 6, 2006
Last Updated: October 9, 2007
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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

Additional relevant MeSH terms:
Vasculitis
Wegener Granulomatosis
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
Azathioprine
Methotrexate
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on April 14, 2014