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Trial record 13 of 49 for:    "Microscopic polyangiitis"

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

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ClinicalTrials.gov Identifier: NCT00987389
Recruitment Status : Completed
First Posted : September 30, 2009
Last Update Posted : March 16, 2018
Sponsor:
Collaborators:
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 ]


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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
Criteria

Inclusion Criteria:

• 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:

    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

      AND

      • 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)

      AND

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

      AND

    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 ClinicalTrials.gov identifier (NCT number): NCT00987389


  Show 98 Study Locations
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)
Investigators
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:
Publications:
Responsible Party: Peter Merkel, Professor, University of Pennsylvania
ClinicalTrials.gov 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
Vasculitis
Granulomatosis with Polyangiitis
Wegener's
ANCA-Associated Vasculitis
GPA
MPA
Treatment
Plasma exchange
Glucocorticoids
ANCA-Positive

Additional relevant MeSH terms:
Microscopic Polyangiitis
Vasculitis
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
Antibodies
Glucocorticoids
Immunologic Factors
Physiological Effects of Drugs
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists