Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial

Trials

David Jayne^1,11  Keith Wheatley⁴  Jeffrey L Winters²  Karen Quillen⁷  William F Clark⁸  Natalie Ives^1,12  Janak deZoysa⁹  Charles D Pusey^1,10  Loïc Guillevin³  Wladimir Szpirt¹  Chen Au Peh^1,13  Peter A Merkel⁵  Michael Walsh⁶ 

[1] Department of Nephrology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark;Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA;Höpital Cochin, Assistance Publique, Hopitaux de Paris, Universite Paris Descartes, Paris, France;Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, University of Birmingham, Birmingham, UK;Division of Rheumatology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA;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;Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA;London Health Sciences Centre, Western University, London, ON, Canada;Department of Renal Medicine, North Shore Hospital, Waitemata District Health Board, Auckland, New Zealand;Department of Medicine, Imperial College London, Hammersmith Hospital, London, UK;Lupus and Vasculitis Clinic, Addenbrooke's Hospital, Cambridge, UK;Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK;Department of Renal Medicine, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia

关键词: ANCA;    Microscopic polyangiitis;    Granulomatosis with polyangiitis;    Vasculitis;    Protocol;    Randomized controlled trial;    Factorial trial;   

Others  :  1094546
DOI  :  10.1186/1745-6215-14-73

 received in 2012-08-13, accepted in 2013-02-28,  发布年份 2013

【 摘 要 】

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 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).

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.

Trial registration

Current Controlled Trials:(ISRCTN07757494) and clinicaltrials.gov:(NCT00987389)

【 授权许可】

   
2013 Walsh et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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