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

NCT ID: NCT00349674

Last Updated: 2007-10-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 126 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-01-31

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.

Conditions

Systemic Wegener's Granulomatosis

Keywords

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: NONE

Interventions

Azathioprine: 2 mg/kg/day

Intervention Type: DRUG

methotrexate 0.3 mg/kg/week, to a maximum and optimal dose of 25 mg/week

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Principal Investigators

Jean-François CORDIER, MD

Role: PRINCIPAL_INVESTIGATOR

Hospices Civils de Lyon

Locations

Christian PAGNOUX

Paris, , France

Countries

France

References

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, Puechal 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.

Reference Type: DERIVED

PMID: 19109574 (View on PubMed)

Other Identifiers

97.129

Identifier Type: -

Identifier Source: org_study_id