Granulomatosis With Polyangiitis (Wegener'
Conditions
Interventions
Experimental plasma exchange (PLEX) in addition to standard immunosuppressive therapy and standard-dose glucocorticoids (GC) taper.
Standard immunosuppressive therapy and standard-dose GC taper witho
Sponsors
Cambridge University Hospitals NHS Foundation Trust, UK
European Vasculitis Study Group Vasculitis Clinical Research Consortium
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. New or previous clinical diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis consistent with the Chapel-Hill consensus definitions AND 2. Positive test, at any point in the subject's course, by ELISA, for proteinase 3-ANCA or myeloperoxidase-ANCA AND 3. Severe vasculitis defined by at least one of the following: a. Renal involvement with both: i. Renal biopsy demonstrating focal necrotizing glomerulonephritis or active urine sediment characterized by glomerular haematuria or red cell casts and proteinuria AND ii. eGFR <50 ml/min/1.73 m2 b. Pulmonary hemorrhage due to active vasculitis defined by: i. A compatible chest x-ray or CT scan (diffuse pulmonary infiltrates) AND ii. The absence of an alternative explanation for all pulmonary infiltrates (e.g. volume overload or pulmonary infection) AND iii. At least one of the following: 1)Evidence of alveolar hemorrhage on bronchoscopic examination or increasingly bloody returns with bronchoalveolar lavage 2)Observed hemoptysis 3)Unexplained anemia (<10 g/dL) or documented drop in hemoglobin >1 g/dL) 4)Increased diffusing capacity of carbon dioxide 4. Provision of informed consent by patient or a surrogate decision maker
Exclusion criteria
Exclusion criteria: 1. A diagnosis of vasculitis other than granulomatosis with polyangiitis or microscopic polyangiitis 2. Positive anti-glomerular basement membrane antibody test or renal biopsy demonstrating linear glomerular immunoglobulin deposition 3. Receipt of dialysis for >21 days immediately prior to randomization or prior renal transplant 4. Age <18 years 5. Pregnancy/Inability or unwillingness to comply with birth control 6. 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 7. A comorbidity or condition that, in the opinion of the investigator,precludes the use of cyclophosphamide/rituximab, glucocorticoids, or plasma exchange or absolutely mandates the use of plasma exchange 8. Plasma exchange in 3 months prior to randomization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Composite of i)all-cause mortality or ii) End-stage renal disease | — |
Secondary
| Measure | Time frame |
|---|---|
| *Sustained remission *Rate of serious infections *Health-related quality of life using the SF-36 Physical Composite, Mental Composite and EQ-5D Index Score | — |
Countries
Japan,North America,South America,Australia,Europe
Contacts
Public ContactToshiko Ito-Ihara
Kyoto University Hospital Institute for Advancement of Clinical and Translational Science
Outcome results
None listed