NORAM 2005.

Methods	Study design: parallel RCT Duration of study: July 1995 to September 2000 Duration of follow‐up: 18 months
Participants	Country: Europe (10 countries) Setting: multicentre (26) Inclusion criteria: new diagnosis of WG or MPA in 1 or more organ systems; elevated ESR or CRP or both or ANCA positivity, or a non‐renal biopsy demonstrating small vessel vasculitis Number: treatment group (49); control group (46) Median age, range (years): treatment group (48.8, 18 to 72); control group (53.5, 22 to 78) Sex (M/F): treatment group (24/25); control group (20/36) Exclusion criteria: organ or life‐threatening vasculitis (severe haemoptysis with bilateral pulmonary infiltrates, cerebral infarction due to vasculitis, rapidly progressive neuropathy, orbital pseudotumour, massive GI bleeding, heart failure due to pericarditis or myocarditis; Cr > 150 µM, urinary red cell casts or proteinuria >1 g/day; skin vasculitis only; another multisystem autoimmune disease; malignancy; hepatitis B or HIV infection; < 18 years or >75 years
Interventions	Treatment group MTX: 15 mg/week oral MTX increasing to 2 5mg/week at week 12, continued to month 10 then tapered to stop at month 12 Control group Oral CPA: group: 2 mg/kg/day (max 150 mg/day) until remission, minimum of 3 months, maximum of 6 months. At remission, dose reduced to 1.5 mg/kg/day continued to month 10 then tapered to stop at month 12. Dose adjusted for age and low WCC Co‐interventions (both groups) Oral prednisolone: 1 mg/kg/day tapered to 15 mg/day at 12 weeks and 7.5 mg/day by 6 months, stopped at 12 months
Outcomes	Primary endpoint Remission at 6 months Secondary endpoints Disease relapse Adverse effects
Notes	Funding: Supported by the European Community Systemic Vasculitis Trial project (grants BMH1‐CT93‐1078 and CIPD‐CT94‐0307) and the Associated Vasculitis European randomised Trial project (grants BMH4‐CT97‐2328 and IC20‐CT97‐0019), which was funded by the European Union.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Centrally in blocks of 4 by country and stratified by diagnosis
Allocation concealment (selection bias)	Low risk	Centrally performed
Blinding of participants and personnel (performance bias) All outcomes	Low risk	States unblinded; unlikely to affect outcomes
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information to permit judgement
Incomplete outcome data (attrition bias) All outcomes	Low risk	Follow‐up losses all stated and counted as treatment failure
Selective reporting (reporting bias)	Low risk	Study and review outcomes reported
Other bias	Low risk	Funding source stated