PMID- 23497590
OWN - NLM
STAT- MEDLINE
DCOM- 20130909
LR  - 20220330
IS  - 1745-6215 (Electronic)
IS  - 1745-6215 (Linking)
VI  - 14
DP  - 2013 Mar 14
TI  - Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil 
      cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized 
      controlled trial.
PG  - 73
LID - 10.1186/1745-6215-14-73 [doi]
AB  - 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).
FAU - Walsh, Michael
AU  - Walsh M
AD  - 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
FAU - Merkel, Peter A
AU  - Merkel PA
FAU - Peh, Chen Au
AU  - Peh CA
FAU - Szpirt, Wladimir
AU  - Szpirt W
FAU - Guillevin, Loic
AU  - Guillevin L
FAU - Pusey, Charles D
AU  - Pusey CD
FAU - De Zoysa, Janak
AU  - De Zoysa J
FAU - Ives, Natalie
AU  - Ives N
FAU - Clark, William F
AU  - Clark WF
FAU - Quillen, Karen
AU  - Quillen K
FAU - Winters, Jeffrey L
AU  - Winters JL
FAU - Wheatley, Keith
AU  - Wheatley K
FAU - Jayne, David
AU  - Jayne D
CN  - PEXIVAS Investigators
LA  - eng
SI  - ISRCTN/ISRCTN07757494
SI  - ClinicalTrials.gov/NCT00987389
GR  - MC_PC_15016/MRC_/Medical Research Council/United Kingdom
GR  - CAPMC/CIHR/Canada
GR  - U54AR057319/AR/NIAMS NIH HHS/United States
GR  - R01FD003516/FD/FDA HHS/United States
GR  - 08/56/04/DH_/Department of Health/United Kingdom
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20130314
PL  - England
TA  - Trials
JT  - Trials
JID - 101263253
RN  - 0 (Glucocorticoids)
SB  - IM
MH  - Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/*therapy
MH  - *Clinical Protocols
MH  - Glucocorticoids/*administration & dosage
MH  - Humans
MH  - *Plasma Exchange
MH  - Sample Size
PMC - PMC3607855
EDAT- 2013/03/19 06:00
MHDA- 2013/09/10 06:00
PMCR- 2013/03/14
CRDT- 2013/03/19 06:00
PHST- 2012/08/13 00:00 [received]
PHST- 2013/02/28 00:00 [accepted]
PHST- 2013/03/19 06:00 [entrez]
PHST- 2013/03/19 06:00 [pubmed]
PHST- 2013/09/10 06:00 [medline]
PHST- 2013/03/14 00:00 [pmc-release]
AID - 1745-6215-14-73 [pii]
AID - 10.1186/1745-6215-14-73 [doi]
PST - epublish
SO  - Trials. 2013 Mar 14;14:73. doi: 10.1186/1745-6215-14-73.