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Background: Granulomatosis with polyangiitis (GPA, Wegener's) and microscopic polyangiitis (MPA) are small vessel vasculitides collectively referred to as anti-neutrophil cytoplasm antibody-associated vasculitis (AAV). AAV is associated with high rates of morbidity and mortality due to uncontrolled disease and treatment toxicity. Small randomized trials suggest adjunctive plasma exchange may improve disease control, while observational evidence suggests that current oral glucocorticoid doses are associated with severe infections in patients with AAV. A randomized study of both plasma exchange and glucocorticoids is required to evaluate plasma exchange and oral glucocorticoid dosing in patients with AAV. Methods/design: PEXIVAS is a two-by-two factorial randomized trial evaluating adjunctive plasma exchange and two oral glucocorticoid regimens in severe AAV. Five hundred patients are being randomized at centers across Europe, North America, Asia, and Australasia to receive plasma exchange or no plasma exchange, and to receive standard or reduced oral glucocorticoid dosing. All patients receive immunosuppression with either cyclophosphamide or rituximab. The primary outcome is the time to the composite of all-cause mortality and endstage renal disease. PEXIVAS is funded by the National Institute of Health Research (UK), the Food and Drug Administration (USA), the National Institutes of Health (USA), the Canadian Institute of Health Research (Canada), the National Health and Medical Research Council (Australia), and Assistance Publique (France). Additional in-kind supplies for plasma exchange are provided by industry partners (TerumoBCT, Gambro Australia, and Fresenius Australia). Discussion: This is the largest trial in AAV undertaken to date. PEXIVAS will inform the future standard of care for patients with severe AAV. The cooperation between investigators, funding agencies, and industry provides a model for conducting studies in rare diseases. [ABSTRACT FROM AUTHOR]