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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by University of Pennsylvania
Sponsor:
Collaborators:
Birmingham Clinical Trials Unit
Cambridge University Hospitals NHS Foundation Trust
Information provided by (Responsible Party):
Peter Merkel, University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00987389
First received: September 23, 2009
Last updated: December 3, 2013
Last verified: November 2013
  Purpose

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 is one of the funding sources for this study.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • All-cause mortality [ Time Frame: 2 years after the final subject is enrolled ] [ Designated as safety issue: Yes ]
  • End-stage renal disease [ Time Frame: 2 years after final subject is enrolled ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Sustained remission [ Time Frame: 2 years after the final subject is enrolled ] [ Designated as safety issue: No ]
    Remission that occurs before 6 months, and lasts without a first relapse until at least 12 months after randomization

  • Rate of serious infections [ Time Frame: 12 months after first subject enrolled and at study end ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 500
Study Start Date: May 2010
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00987389

  Show 72 Study Locations
Sponsors and Collaborators
University of Pennsylvania
Birmingham Clinical Trials Unit
Cambridge University Hospitals NHS Foundation Trust
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
  More Information

Additional Information:
No publications provided by University of Pennsylvania

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Peter Merkel, Professor, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00987389     History of Changes
Other Study ID Numbers: PEXIVAS, R01FD00351604
Study First Received: September 23, 2009
Last Updated: December 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:
Granulomatosis with Polyangiitis
Vasculitis
Microscopic Polyangiitis
Wegener's
ANCA-Associated Vasculitis
GPA
MPA
Treatment
Plasma exchange
Glucocorticoids
ANCA-Positive

Additional relevant MeSH terms:
Wegener Granulomatosis
Vasculitis
Systemic Vasculitis
Microscopic Polyangiitis
Vascular Diseases
Cardiovascular Diseases
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Autoimmune Diseases
Immune System Diseases
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014