ANCA associated vasculitis Circulatory System ANCA associated vasculitis
Conditions
Interventions
Drug regimens:
1. Rituximab regimen: rituximab, 375 mg/m2 IV once a week for four weeks (i.e. four doses total), with two doses of cyclophosphamide 15 mg/kg, two weeks apart given with the first and t
Sponsors
Cambridge University Hospitals NHS Foundation Trust (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. A new diagnosis of Wegener's Granulomatosis (WG), Microscopic Polyangiitis (MP) or Renal-Limited Vasculitis (RLV) 2. Renal involvement attributable to active WG, MP or RLV with at least one of the following: 2.1. Biopsy demonstrating necrotizing glomerulonephritis 2.2. Red cell casts on urine microscopy or =++ haematuria 3. Anti-Neutrophilic Cytoplasmic Antibodies (ANCA) positivity; ANCA positivity requires either: 3.1. Proteinase 3 anti-neutrophilic cytoplasmic antibody (PR3-ANCA) by Enzyme-Linked Immunosorbent Assay (ELISA) or a typical antineutrophil cytoplasmic antibody (cANCA) pattern by indirect immunofluorescence (IIF), or both 3.2. Myeloperoxidase- anti-neutrophilic cytoplasmic antibody (MPO-ANCA) by ELISA. A positive perinuclear anti-neutrophilic cytoplasmic antibody (pANCA) by IIF requires confirmation by MPO-ANCA ELISA 4. Written informed consent
Exclusion criteria
Exclusion criteria: 1. Previous cyclophosphamide, (greater than two weeks of an oral or intravenous [IV] pulse cyclophosphamide regimen) 2. Co-existence of another multisystem autoimmune disease, e.g. SLE, Churg Strauss syndrome, Henoch Schonlein purpura, rheumatoid vasculitis, essential mixed cryoglobulinaemia, anti-glomerular basement membrane antibody positivity 3. Hepatitis B antigen positive or hepatitis C antibody positive 4. Known HIV positive (HIV testing will not be a requirement for this trial) 5. Previous malignancy (usually exclude unless agreed with trial co-ordinator) 6. Pregnancy, breast feeding or inadequate contraception if female 7. Allergy to a study medication 8. Live vaccine within last four weeks
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Sustained remission (Birmingham Vasculitis Assessment Score [BVAS] = 0 at six months and sustained for six months) 2. Severe adverse events (Common Terminology Criteria for Adverse Events [CTCAE] grade =3) at two years | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Efficacy 1.1. Response rate at six weeks (BVAS <50% baseline) 1.2. Remission at six months (BVAS = 0 for 2 months by 6 months) 1.3. Time to remission (BVAS = 0) 1.4. Relapses (all relapses and major or minor) 1.5. BVAS area under the curve 1.6. Change in Glomerular Filtration Rate (GFR) 1.7. Change in SF-36 1.8. Change in Venous Distensibility Index (VDI) 2. Safety 2.1. Severe adverse events (CTCAE grade =3) at six weeks and six months 2.2. All adverse events 2.3. Death 2.4. Prednisolone cumulative dose 2.5. Cyclophosphamide cumulative dose | — |
Countries
Australia, Czech Republic, Germany, Mexico, Netherlands, Sweden, Switzerland, United Kingdom
Outcome results
None listed