Plasma Exchange and Glucocorticoids for Treatment of Anti-Neutrophil Cytoplasm Antibody (ANCA) - Associated Vasculitis
PEXIVAS
3 other identifiers
interventional
704
15 countries
98
Brief Summary
The purpose of this study is to determine whether plasma exchange as well as immunosuppressive therapy are effective in reducing death and end-stage renal disease (ESRD). The trial will also study whether a reduced cumulative dosing regimen of glucocorticoids is as effective as a standard disease regimen. The FDA-OOPD is one of the funding sources for this study.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started May 2010
Longer than P75 for phase_3
98 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 23, 2009
CompletedFirst Posted
Study publicly available on registry
September 30, 2009
CompletedStudy Start
First participant enrolled
May 1, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2017
CompletedResults Posted
Study results publicly available
May 26, 2020
CompletedMay 26, 2020
May 1, 2020
7.3 years
September 23, 2009
October 31, 2018
May 19, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Composite of i) All-cause Mortality or ii) End-stage Renal Disease
The primary outcome was a composite of death from any cause or end-stage renal disease (ESRD), defined as ≥12 continuous weeks of renal replacement therapy.
Time frame varied by subject: minimum of 1 year - maximum of 7 years
Secondary Outcomes (5)
Number of Participants With Sustained Remission
Time frame varied by subject: minimum of 1 year - maximum of 7 years
Rate of Serious Infection Events
Time frame varied by subject: minimum of 1 year - maximum of 7 years
Health-related Quality of Life Using the SF-36 Physical Composite
12 months
Health-related Quality of Life Using the SF-36 Mental Composite
12 months
Health-related Quality of Life Using the EQ-5D Index Descriptive System
12 months
Study Arms (4)
Plasma Exchange with Standard Glucocorticoids
EXPERIMENTALParticipants in this arm undergo plasma exchange and take a standard glucocorticoid dose.
No Plasma Exchange with Standard Glucocorticoids
ACTIVE COMPARATORParticipants in this arm do not undergo plasma exchange and take a standard glucocorticoid dose.
Plasma Exchange with Reduced-Dose Glucocorticoids
EXPERIMENTALParticipants in this arm undergo plasma exchange and take a reduced glucocorticoid dose.
No Plasma Exchange with Reduced-Dose Glucocorticoids
ACTIVE COMPARATORParticipants in this arm do not undergo plasma exchange and take a reduced glucocorticoid dose.
Interventions
Plasma exchange is a procedure whereby blood is taken from the body and separated by a machine into blood cells and plasma, which is the liquid part of blood. The plasma is discarded and the blood cells are returned to the body with a plasma substitute.
No plasma exchange.
During the study, a standard glucocorticoids dose regimen will be compared to a reduced glucocorticoids dose regimen. All subjects' patients will receive the same glucocorticoids dose for the first two weeks then the dose will decrease following a standard regimen.
During the study, a standard glucocorticoids dose regimen will be compared to a reduced glucocorticoids dose regimen. All subjects' patients will receive the same glucocorticoids dose for the first two weeks then the dose will decrease following a reduced regimen.
Eligibility Criteria
You may qualify if:
- New or previous clinical diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis consistent with the Chapel-Hill consensus definitions
- AND
- Positive test for proteinase 3-ANCA or myeloperoxidase-ANCA
- AND
- Severe vasculitis defined by at least one of the following:
- Renal involvement characterized by both of the following:
- Renal biopsy demonstrating focal necrotizing glomerulonephritis or active urine sediment characterized by glomerular haematuria or red cell casts and proteinuria
- AND
- eGFR \<50 ml/min/1.73 m2
- Pulmonary hemorrhage due to active vasculitis defined by:
- A compatible chest x-ray or CT scan (diffuse pulmonary infiltrates)
- AND
- The absence of an alternative explanation for all pulmonary infiltrates (e.g. volume overload or pulmonary infection)
- AND
- At least one of the following:
- +5 more criteria
You may not qualify if:
- A diagnosis of vasculitis other than granulomatosis with polyangiitis or microscopic polyangiitis
- Positive serum anti-glomerular basement membrane antibody test or renal biopsy demonstrating linear glomerular immunoglobulin deposition
- Receipt of dialysis for \>21 days immediately prior to randomization or prior renal transplant
- Age \<15 years
- Pregnancy at time of study entry
- Treatment with \>1 IV dose of cyclophosphamide and/or \>14 days of oral cyclophosphamide and/or \>14 days of prednisone/prednisolone (\>30 mg/day) and/or \>1 dose of rituximab within the 28 days immediately prior to randomization
- A comorbidity that, in the opinion of the investigator, precludes the use of cyclophosphamide, glucocorticoids, or plasma exchange or absolutely mandates the use of plasma exchange
- Plasma exchange in 3 months prior to randomization
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (98)
Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
Boston University School of Medicine
Boston, Massachusetts, 02118, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Washington University School of Medicine
St Louis, Missouri, United States
University of North Carolina
Chapel Hill, North Carolina, 27599, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213, United States
University of Virginia
Charlottesville, Virginia, 22904, United States
Canberra Hospital
Garran, Australian Capital Territory, Australia
Concord Repatriation General Hospital
Concord, New South Wales, Australia
John Hunter Hospital,
New Lambton Heights, New South Wales, Australia
Prince of Wales Hospital
Randwick, New South Wales, Australia
Royal North Shore Hospital
St Leonards, New South Wales, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia
Nambour Hospital
Nambour, Queensland, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
Flinders Medical Centre,
Adelaide, South Australia, Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia
Royal Hobart Hospital
Hobart, Tasmania, Australia
Monash Medical Centre
Clayton, Victoria, Australia
St Vincent's Hospital
Fitzroy, Victoria, Australia
The Geelong Hospital
Geelong, Victoria, Australia
Austin Hospital
Heidelberg, Victoria, Australia
The Royal Melbourne Hospital
Parkville, Victoria, Australia
Fremantle Hospital,
Fremantle, Western Australia, Australia
Gold Coast Hospital
Southport, Australia
University Hospitals Leuven
Leuven, Belgium
University of Calgary
Calgary, Alberta, Canada
University of Alberta
Edmonton, Alberta, Canada
St Paul's Hospital
Vancouver, British Columbia, Canada
St Joseph's Hospital
Hamilton, Ontario, Canada
London Health Sciences Centre
London, Ontario, Canada
The Ottawa Hospital
Ottawa, Ontario, Canada
Mount Sinai Hospital
Toronto, Ontario, Canada
St Michael's Hospital
Toronto, Ontario, Canada
Hopital Saint-Luc
Montreal, Quebec, H2X 3J4, Canada
General Faculty Hospital
Prague, Czechia
Aarhus University Hospital
Aarhus, Denmark
Herlev Hospital
Copenhagen, Denmark
Rigshospitalet
Copenhagen, Denmark
Holstebro Hospital and University of Aarhus
Holstebro, Denmark
Centre Hospitalier de Boulogne
Boulogne-sur-Mer, France
CHRU Brest Hopital La Cavale Blanche
Brest, France
CHU Brest
Brest, France
CHU Caen - Nephrology Department
Caen, France
CHU Clermont-Ferrand
Clermont-Ferrand, France
Colmar Hospital - Nephrology
Colmar, France
CHU D'Angers
D'Angers, France
Centre Hospitalier Universitaire de Grenoble
Grenoble, France
Hopital Site Sainte Blandine
Metz, France
Centre Hospitalier de Mulhouse
Mulhouse, France
Hopital Bichat Claude Bernard
Paris, France
Hopital Cochin
Paris, France
Hopital Europeen Georges-Pompidou
Paris, France
Centre Hospitalier de la Region d'Annecy
Pringy, France
CHU De Toulouse-Hotel Dieu Saint Jacques
Toulouse, France
CHU Hopital Bretonneau
Tours, France
Centre Hospitalier de Valenciennes
Valenciennes, France
Hippokration Hospital
Thessaloniki, Greece
University of Brescia
Brescia, Italy
Azienda Ospedaliero Universitaria di Parma
Parma, Italy
University of Tsukuba
Tsukuba, Ibaraki, 305-8572, Japan
Kyoto University Hospital
Kyoto, 606-8507, Japan
University of Miyazaki Hospital
Miyazaki, Japan
Kitano Hospital
Osaka, Japan
Teikyo University Hospital
Tokyo, Japan
Tokyo Metropolitan Geriatric Hospital
Tokyo, Japan
Instituto Nacional de Enfermedades Respiratorias
Mexico City, Mexico
North Shore Hospital
Takapuna, Auckland, New Zealand
Dunedin Hospital
Dunedin, New Zealand
Waikato Hospital
Hamilton, 3204, New Zealand
University Hospital North Norway HF
Tromsø, Norway
St Olavs Hospital, Trondheim University Hospital
Trondheim, Norway
Linkoping University Hospital
Linköping, Sweden
Skane University Hospital
Malmo, Sweden
Karolinska Institute
Stockholm, Sweden
Western Infirmary
Glasgow, Scotland, United Kingdom
Aberdeen Royal Infirmary
Aberdeen, AB25 2, United Kingdom
Queen Elizabeth Hospital
Birmingham, B15 2TQ, United Kingdom
Brighton and Sussex University Hospitals
Brighton, BN2 5BE, United Kingdom
Addenbrooke's Hospital
Cambridge, CB22QQ, United Kingdom
Kent and Canterbury Hospital
Canterbury, United Kingdom
University Hospitals Coventry and Warwickshire NHS Trust
Coventry, CV2 2DX, United Kingdom
Royal Infirmary of Edinburgh
Edinburgh, EH16 4SA, United Kingdom
Royal Devon & Exeter Hospital (Wonford)
Exeter, United Kingdom
St James's University Hospital
Leeds, United Kingdom
Royal Liverpool University Hospital
Liverpool, L7 8XP, United Kingdom
Royal Free Hospital
London, NW3 2QG, United Kingdom
The Royal London Hospital
London, SE1 2PR, United Kingdom
St. George's Hospital
London, SW17 0QT, United Kingdom
Hammersmith Hospital
London, W12 0HS, United Kingdom
Manchester Royal Infirmary
Manchester, United Kingdom
Freeman Hospital
Newcastle, United Kingdom
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences
Oxford, OX3 7LD, United Kingdom
Churchill Hospital
Oxford, OX3 7LJ, United Kingdom
Royal Preston Hospital
Preston, PR2 9HT, United Kingdom
Royal Berkshire Hospital, Reading
Reading, RG1 5AQ, United Kingdom
Related Publications (4)
Walsh M, Merkel PA, Peh CA, Szpirt W, Guillevin L, Pusey CD, De Zoysa J, Ives N, Clark WF, Quillen K, Winters JL, Wheatley K, Jayne D; PEXIVAS Investigators. Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial. Trials. 2013 Mar 14;14:73. doi: 10.1186/1745-6215-14-73.
PMID: 23497590BACKGROUNDWalsh M, Merkel PA, Peh CA, Szpirt WM, Puechal X, Fujimoto S, Hawley CM, Khalidi N, Flossmann O, Wald R, Girard LP, Levin A, Gregorini G, Harper L, Clark WF, Pagnoux C, Specks U, Smyth L, Tesar V, Ito-Ihara T, de Zoysa JR, Szczeklik W, Flores-Suarez LF, Carette S, Guillevin L, Pusey CD, Casian AL, Brezina B, Mazzetti A, McAlear CA, Broadhurst E, Reidlinger D, Mehta S, Ives N, Jayne DRW; PEXIVAS Investigators. Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis. N Engl J Med. 2020 Feb 13;382(7):622-631. doi: 10.1056/NEJMoa1803537.
PMID: 32053298RESULTFussner LA, Flores-Suarez LF, Cartin-Ceba R, Specks U, Cox PG, Jayne DRW, Merkel PA, Walsh M; PEXIVAS Investigators. Alveolar Hemorrhage in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Results of an International Randomized Controlled Trial (PEXIVAS). Am J Respir Crit Care Med. 2024 May 1;209(9):1141-1151. doi: 10.1164/rccm.202308-1426OC.
PMID: 38346237DERIVEDJayne D, Walsh M, Merkel PA, Peh CA, Szpirt W, Puechal X, Fujimoto S, Hawley C, Khalidi N, Jones R, Flossmann O, Wald R, Girard L, Levin A, Gregorini G, Harper L, Clark W, Pagnoux C, Specks U, Smyth L, Ito-Ihara T, de Zoysa J, Brezina B, Mazzetti A, McAlear CA, Reidlinger D, Mehta S, Ives N, Brettell EA, Jarrett H, Wheatley K, Broadhurst E, Casian A, Pusey CD. Plasma exchange and glucocorticoids to delay death or end-stage renal disease in anti-neutrophil cytoplasm antibody-associated vasculitis: PEXIVAS non-inferiority factorial RCT. Health Technol Assess. 2022 Sep;26(38):1-60. doi: 10.3310/PNXB5040.
PMID: 36155131DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Michael Walsh
- Organization
- McMaster University, Hamilton, Ontario
Study Officials
- PRINCIPAL INVESTIGATOR
David Jayne, MD
Cambridge University Hospitals NHS Foundation Trust
- PRINCIPAL INVESTIGATOR
Peter Merkel, MD, MPH
University of Pennsylvania
- PRINCIPAL INVESTIGATOR
Michael Walsh, MD
McMaster University
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- FACTORIAL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
September 23, 2009
First Posted
September 30, 2009
Study Start
May 1, 2010
Primary Completion
August 1, 2017
Study Completion
August 1, 2017
Last Updated
May 26, 2020
Results First Posted
May 26, 2020
Record last verified: 2020-05