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

 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 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