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

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: NCT03919825
Recruitment Status : Completed
First Posted : April 18, 2019
Last Update Posted : April 18, 2019
Information provided by (Responsible Party):
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) Drug: Glucocorticoids - Standard Dose Drug: Glucocorticoids - Reduced Dose 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 704 participants
Allocation: Randomized
Intervention Model: Parallel 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 [Glucocorticoids]
Actual Study Start Date : May 2010
Actual Primary Completion Date : August 2017
Actual Study Completion Date : August 31, 2017

Arm Intervention/treatment
Active Comparator: Glucocorticoids - Standard Dose
All subjects' patients will receive the same glucocorticoids dose for the first two weeks then the dose will decrease following a standard regimen.
Drug: Glucocorticoids - Standard Dose
Subjects will receive glucocorticoids at a standard dose and will decrease following a standard regimen.

Experimental: Glucocorticoids - Reduced Dose
All subjects' patients will receive the same glucocorticoids dose for the first two weeks then the dose will decrease following a reduced dose regimen.
Drug: Glucocorticoids - Reduced Dose
Subjects' will receive glucocorticoids at a reduced dose and will decrease following a reduced dose 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 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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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): NCT03919825

Sponsors and Collaborators
University of Pennsylvania
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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:
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Responsible Party: University of Pennsylvania Identifier: NCT03919825     History of Changes
Other Study ID Numbers: 5524
First Posted: April 18, 2019    Key Record Dates
Last Update Posted: April 18, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of Pennsylvania:
Additional relevant MeSH terms:
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Granulomatosis with Polyangiitis
Microscopic Polyangiitis
Systemic Vasculitis
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