title: Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial.
abstract: 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
  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 end-stage 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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Current Controlled Trials: (ISRCTN07757494) and clinicaltrials.gov: (NCT00987389).
authors.affiliation: Departments of Medicine and Clinical Epidemiology & Biostatistics, Marian Wing, Division of Nephrology, McMaster University, St, Joseph's Hospital, 50 Charlton Ave East, Hamilton, ON L8S 4A6, Canada. lastwalsh1975@gmail.com
authors.forename: Michael
authors.initials: M
authors.lastname: Walsh
authors.forename: Peter A
authors.initials: PA
authors.lastname: Merkel
authors.forename: Chen Au
authors.initials: CA
authors.lastname: Peh
authors.forename: Wladimir
authors.initials: W
authors.lastname: Szpirt
authors.forename: Loïc
authors.initials: L
authors.lastname: Guillevin
authors.forename: Charles D
authors.initials: CD
authors.lastname: Pusey
authors.forename: Janak
authors.initials: J
authors.lastname: De Zoysa
authors.forename: Natalie
authors.initials: N
authors.lastname: Ives
authors.forename: William F
authors.initials: WF
authors.lastname: Clark
authors.forename: Karen
authors.initials: K
authors.lastname: Quillen
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Winters
authors.forename: Keith
authors.initials: K
authors.lastname: Wheatley
authors.forename: David
authors.initials: D
authors.lastname: Jayne
mesh_terms: D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000628:therapy*; D002985:Clinical Protocols; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D010951:Plasma Exchange; D018401:Sample Size
chemical_list: D005938:Glucocorticoids