Plasma Exchange and Glucocorticoids for Treatment of Anti-Neutrophil Cytoplasm Antibody (ANCA) - Associated Vasculitis (PEXIVAS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00987389
Recruitment Status : Completed
First Posted : September 30, 2009
Last Update Posted : March 16, 2018
Cambridge University Hospitals NHS Foundation Trust
University of Birmingham
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
Peter Merkel, University of Pennsylvania

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.

Condition or disease Intervention/treatment Phase
Granulomatosis With Polyangiitis (Wegener's) (GPA) Microscopic Polyangiitis (MPA) Procedure: Plasma Exchange Drug: Glucocorticoids Phase 3

Detailed Description:

Granulomatosis with polyangiitis (Wegener's) (WG) and microscopic polyangiitis (MPA) are syndromes of primary systemic vasculitis associated with anti-neutrophil cytoplasm antibodies (ANCA). Together, these syndromes are grouped as ANCA-associated systemic vasculitis (AAV).

Plasma exchange, a method of rapidly removing potentially pathogenic ANCA and other mediators of inflammation and coagulation, has shown promise as an adjunctive therapy in AAV to improve early disease control and improve rates of renal recovery in severe disease. Glucocorticoids (steroids) are a standard of care in the treatment of AAV. High doses of glucocorticoids early in disease, although reduce disease activity due to their anti-inflammatory and immunosuppressive properties, also increase the risk of infection, particularly in the elderly and in the presence of uremia. There is no randomized trial data to guide glucocorticoids dosing.

Patients with severe new or relapsing AAV and pulmonary hemorrhage and/or renal disease will be eligible for this trial.

Subjects participating in this study will be randomized to receive one of the following groups;

  1. Plasma exchange - 7 exchanges and, either standard or low-dose glucocorticoids or
  2. No plasma exchange and, either standard or low-dose glucocorticoids

All studies will receive standard remission-induction therapy with either cyclophosphamide or rituximab.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 704 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Plasma Exchange and Glucocorticoid Dosing in the Treatment of Anti-neutrophil Cytoplasm Antibody Associated Vasculitis: an International Randomized Controlled Trial
Actual Study Start Date : May 2010
Actual Primary Completion Date : August 2017
Actual Study Completion Date : August 2017

Arm Intervention/treatment
No Plasma Exchange
Participants in this arm do not undergo plasma exchange
Drug: Glucocorticoids
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 either a standard regimen or a reduced regimen.

Experimental: Plasma Exchange Procedure: Plasma Exchange
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.

Drug: Glucocorticoids
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 either a standard regimen or a reduced regimen.

Primary Outcome Measures :
  1. Composite of i) all-cause mortality or ii) End-stage renal disease [ Time Frame: 2 years after the final subject is enrolled ]

Secondary Outcome Measures :
  1. Sustained remission [ Time Frame: 2 years after the final subject is enrolled ]
    Remission that occurs before 6 months, and lasts without a first relapse until at least 12 months after randomization

  2. Rate of serious infections [ Time Frame: 12 months after first subject enrolled and at study end ]
  3. Health-related quality of life using the SF-36 Physical Composite, Mental Composite and EQ-5D Index Score [ Time Frame: 12 months after study enrollment is completed ]

Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

• New or previous clinical diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis consistent with the Chapel-Hill consensus definitions


• Positive test for proteinase 3-ANCA or myeloperoxidase-ANCA


  • Severe vasculitis defined by at least one of the following:

    1. Renal involvement with both:

      • Renal biopsy demonstrating focal necrotizing glomerulonephritis or active urine sediment characterized by glomerular haematuria or red cell casts and proteinuria


      • eGFR <50 ml/min/1.73 m2
    2. Pulmonary hemorrhage due to active vasculitis defined by:

      • A compatible chest x-ray or CT scan (diffuse pulmonary infiltrates)


      • The absence of an alternative explanation for all pulmonary infiltrates (e.g. volume overload or pulmonary infection)


    3. At least one of the following:

      • Evidence of alveolar hemorrhage on bronchoscopic examination or increasingly bloody returns with bronchoalveolar lavage
      • Observed hemoptysis
      • Unexplained anemia (<10 g/dL) or documented drop in hemoglobin >1 g/dL)
      • Increased diffusing capacity of carbon dioxide
  • Provision of informed consent by patient or a surrogate decision maker

Exclusion Criteria:

  • A diagnosis of vasculitis other than granulomatosis with polyangiitis or microscopic polyangiitis
  • Positive 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
  • Inability or unwillingness to comply with birth control/abstinence
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00987389

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United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
United States, Massachusetts
Boston University School of Medicine
Boston, Massachusetts, United States, 02118
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States
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University of North Carolina
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
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University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
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University of Virginia
Charlottesville, Virginia, United States, 22904
Australia, Australian Capital Territory
Canberra Hospital
Garran, Australian Capital Territory, Australia
Australia, New South Wales
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
Australia, Queensland
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia
Nambour Hospital
Nambour, Queensland, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
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Adelaide, South Australia, Australia
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Adelaide, South Australia, Australia
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Hobart, Tasmania, Australia
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Clayton, Victoria, Australia
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Fitzroy, Victoria, Australia
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Geelong, Victoria, Australia
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Heidelberg, Victoria, Australia
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Parkville, Victoria, Australia
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Aarhus, Denmark
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Boulogne-sur-Mer, France
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Brest, France
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Brest, France
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Caen, France
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Clermont Ferrand, France
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Colmar, France
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D'Angers, France
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Grenoble, France
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Metz, France
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Mulhouse, France
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Paris, France
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Pringy, France
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Toulouse, France
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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, Japan, 305-8572
Kyoto University Hospital
Kyoto, Japan, 606-8507
University of Miyazaki Hospital
Miyazaki, Japan
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Osaka, Japan
Teikyo University Hospital
Tokyo, Japan
Tokyo Metropolitan Geriatric Hospital
Tokyo, Japan
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Mexico City, Mexico
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Takapuna, Auckland, New Zealand
Dunedin Hospital
Dunedin, New Zealand
Waikato Hospital
Hamilton, New Zealand, 3204
University Hospital North Norway HF
Tromsø, Norway
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Trondheim, Norway
Linkoping University Hospital
Linkoping, Sweden
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Malmo, Sweden
Karolinska Institute
Stockholm, Sweden
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Glasgow, Scotland, United Kingdom
Aberdeen Royal Infirmary
Aberdeen, United Kingdom, AB25 2
Queen Elizabeth Hospital
Birmingham, United Kingdom, B15 2TQ
Brighton and Sussex University Hospitals
Brighton, United Kingdom, BN2 5BE
Addenbrooke's Hospital
Cambridge, United Kingdom, CB22QQ
Kent and Canterbury Hospital
Canterbury, United Kingdom
University Hospitals Coventry and Warwickshire NHS Trust
Coventry, United Kingdom, CV2 2DX
Royal Infirmary of Edinburgh
Edinburgh, United Kingdom, EH16 4SA
Royal Devon & Exeter Hospital (Wonford)
Exeter, United Kingdom
St James's University Hospital
Leeds, United Kingdom
Royal Liverpool University Hospital
Liverpool, United Kingdom, L7 8XP
Royal Free Hospital
London, United Kingdom, NW3 2QG
The Royal London Hospital
London, United Kingdom, SE1 2PR
St. George's Hospital
London, United Kingdom, SW17 0QT
Hammersmith Hospital
London, United Kingdom, W12 0HS
Manchester Royal Infirmary
Manchester, United Kingdom
Freeman Hospital
Newcastle, United Kingdom
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences
Oxford, United Kingdom, OX3 7LD
Churchill Hospital
Oxford, United Kingdom, OX3 7LJ
Royal Preston Hospital
Preston, United Kingdom, PR2 9HT
Royal Berkshire Hospital, Reading
Reading, United Kingdom, RG1 5AQ
Sponsors and Collaborators
University of Pennsylvania
Cambridge University Hospitals NHS Foundation Trust
University of Birmingham
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
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

Additional Information:
Responsible Party: Peter Merkel, Professor, University of Pennsylvania Identifier: NCT00987389     History of Changes
Other Study ID Numbers: PEXIVAS
R01FD00351604 ( Other Grant/Funding Number: Food and Drug Administration (FDA) )
2009-013220-24 ( EudraCT Number )
First Posted: September 30, 2009    Key Record Dates
Last Update Posted: March 16, 2018
Last Verified: March 2018

Keywords provided by Peter Merkel, University of Pennsylvania:
Microscopic Polyangiitis
Granulomatosis with Polyangiitis
ANCA-Associated Vasculitis
Plasma exchange

Additional relevant MeSH terms:
Microscopic Polyangiitis
Systemic Vasculitis
Granulomatosis with Polyangiitis
Vascular Diseases
Cardiovascular Diseases
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Autoimmune Diseases
Immune System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Immunologic Factors
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists