Clinical trial NCT00751517: Cyclophosphamide Versus Methotrexate for Remission Maintenance in Systemic Necrotizing Vasculitides
Official title: Cyclophosphamide Versus Methotrexate for Remission Maintenance in Systemic Necrotizing Vasculitides. A Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Wegener's Granulomatosis
Churg-Strauss Syndrome
Microscopic Polyangiitis
Polyarteritis Nodosa
Keywords: Vasculitis
Cyclophosphamide
Methotrexate
Systemic Necrotizing Vasculitides
Lead sponsor: University of Parma
Sponsor class: OTHER
First posted: 2008-09-12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The Systemic Necrotizing Vasculitides (SNV) encompass a group of rare diseases which include Wegener's Granulomatosis (WG), Churg-Strauss Syndrome (CSS), Microscopic polyangiitis (MPA)and Polyarteritis nodosa (PAN). Common histological findings are inflammation with fibrinoid necrosis of the small vessels and sporadic or absent immune-deposits. The gold standard therapy for SNV is currently represented by the association of Cyclophosphamide and Prednisone. The limits of this approach are the high frequency of recurrent disease and an increased incidence of malignancy and infections. The aim of the present study is to compare the efficacy of Methotrexate vs Cyclophosphamide for Remission Maintenance in SNV.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of clinically active SNV
* Life-expectancy \> 1 year
* Written informed consent

Exclusion Criteria:

* Creatinine clearance \< 10 ml/min/1.73 mq
* Aminotransferase levels more than twice the upper limit of the normal range
* HBsAg positivity
* anti-HCV Ig and HCV-RNA positivity
* HIV positivity
* Active malignancies
* Coexistence of connective tissue disease
* Prednisolone, cyclophosphamide or methotrexate hypersensitivity
* Pregnancy

Primary outcomes:
measure: Time from remission to relapse
Secondary outcomes:
measure: Recurrence rate
measure: Therapy-related toxicity
measure: Hospitalization rate
measure: Mortality
Other outcomes:
Locations:
city: Parma
country: Italy
facility: Department of Clinical Medicine Nephrology and Health Science, Parma University Hospital
state: Italy/Parma
Study officials:
affiliation: University of Parma
name: Carlo Buzio, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, Rottem M, Fauci AS. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992 Mar 15;116(6):488-98. doi: 10.7326/0003-4819-116-6-488.
citation: Hoffman GS. Wegener's granulomatosis. Curr Opin Rheumatol. 1993 Jan;5(1):11-7. doi: 10.1097/00002281-199305010-00003.
citation: Gordon M, Luqmani RA, Adu D, Greaves I, Richards N, Michael J, Emery P, Howie AJ, Bacon PA. Relapses in patients with a systemic vasculitis. Q J Med. 1993 Dec;86(12):779-89.
citation: Falk RJ, Jennette JC. ANCA small-vessel vasculitis. J Am Soc Nephrol. 1997 Feb;8(2):314-22. doi: 10.1681/ASN.V82314. No abstract available.
citation: Talar-Williams C, Hijazi YM, Walther MM, Linehan WM, Hallahan CW, Lubensky I, Kerr GS, Hoffman GS, Fauci AS, Sneller MC. Cyclophosphamide-induced cystitis and bladder cancer in patients with Wegener granulomatosis. Ann Intern Med. 1996 Mar 1;124(5):477-84. doi: 10.7326/0003-4819-124-5-199603010-00003.
citation: Maritati F, Alberici F, Oliva E, Urban ML, Palmisano A, Santarsia F, Andrulli S, Pavone L, Pesci A, Grasselli C, Santi R, Tumiati B, Manenti L, Buzio C, Vaglio A. Methotrexate versus cyclophosphamide for remission maintenance in ANCA-associated vasculitis: A randomised trial. PLoS One. 2017 Oct 10;12(10):e0185880. doi: 10.1371/journal.pone.0185880. eCollection 2017.