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

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Unknown status

CT.gov ID

NCT00349674

Collaborator

(none)

126

Enrollment

Location

Study Details

Study Description

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 Design

Study Type:

Interventional

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 :

Jan 1, 1999

Outcome Measures

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. []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.