Plasma Exchange and Glucocorticoids for Treatment of Anti-Neutrophil Cytoplasm Antibody (ANCA) - Associated Vasculitis
Condition: Granulomatosis With Polyangiitis (Wegener's) (GPA); Microscopic Polyangiitis (MPA)
MeSH terms: Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Vasculitis; Systemic Vasculitis
Intervention: Plasma Exchange; No Plasma Exchange; Glucocorticoids [Standard Dose]; Glucocorticoids [Reduced Dose]
Intervention description: 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.; No plasma exchange.; 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 a standard regimen.; 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 a reduced regimen.
Intervention MeSH terms: Glucocorticoids
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Enrollment: 704.0
Sex: All
Minimum age: 15 Years
Healthy volunteers: No
Keywords: Vasculitis; Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Wegener's; ANCA-Associated Vasculitis; GPA; MPA; Treatment; Plasma exchange; Glucocorticoids; ANCA-Positive

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.
    

Eligibility 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 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