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

• Status: Completed
• Trial end date: 2017-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Pennsylvania
• Collaborators: Cambridge University Hospitals NHS Foundation Trust; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); University of Birmingham
• Treatments: Antibodies; Glucocorticoids

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