The purpose is to improve the treatment of a group of rare, multisystem diseases defined below in order to save lives and improve the quality of life for survivors.
Four RCTs will test new therapeutic approaches aiming at:
- improving disease control with intravenous immunoglobulin or sulfamethoxazole/ trimethoprim in addition to standard treatment.
- Lowering cyclophosphamide toxicity by replacing continuous oral treatment with pulsed intravenous administration
- reducing relapse rate by elimination of nasal carriage of Staphylococcus aureus
- reducing relapse rate by long-term, low dose azathioprine treatment in place of treatment withdrawal.
Anti-neutrophil cytoplasm autoantibody (ANCA)-associated systemic vasculitis (MSV) is a group of severe, multisystem, autoimmune diseases (e. g. Wegener's granulomatosis and microscopic polyangiitis), which cause marked incapacity and chronic morbidity due to irreversible organ damage, such as renal failure. The incidence of AASV is increasing, especially in the elderly, and exceeds 25/million/year. Care outside specialist centres is often fragmented and treatment suboptimal. The toxicity of current treatments contributes to incapacity through high cumulative exposure to steroid and cytotoxic drugs. This concerted action will improve the efficacy of treatment, reduce disease-induced damage and minimise drug toxicity by testing frontline theories on improvement of therapy based on recent concepts on pathogenesis.
The four RCTs described above will utilise innovative statistical techniques and trial methodology. Prognostic markers and surrogate end-points will be defined to optimise clinical decision making by identifying patient subgroups and will contribute to the design of a further series of RCTs to test new drugs currently in pilot studies.
Previous European, multidisciplinary collaboration has standardised ANCA assays and diagnostic criteria (EC/BCR, 7 centres 1990-1994) and has designed scoring tools and harmonised treatment through a series of RCTs comparing existing regimens (BIOMED 1, ECSYSVASTRIAL, 18 centres 1994, 90 centres in 15 countries 1996). Increasing participation has maximised the dissemination of the results obtained to routine clinical pratice. Industrial collaboration for the present RCTs has been agreed with four pharmaceutical companies. Central facilities, dependent on reinforced concertation, will be made available for the quality control of serology and histopathology for RCT administration and central database and for training of participants in disease scoring and trial methodology. They will develop into Eurofacilities to support future studies, including public health research, systematic reviews, meta-analysis and the targeted training of young researchers.