Anti-neutrophil cytoplasm antibody associated vasculitis (AAV) with nephritis or lung haemorrhage Mental and Behavioural Disorders Other necrotising vasculopathies
Conditions
Interventions
1. Plasma exchange (seven exchanges of human albumin at a dose of 60 ml/kg over 14 days) as an adjunctive therapy to standard immunosuppression treatment and glucocorticoids
2. A reduc
Sponsors
Cambridge University Hospitals NHS Foundation Trust (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. New or previous clinical diagnosis of Wegener's granulomatosis, or microscopic polyangiitis consistent with the Chapel-Hill consensus definitions 2. Positive test for proteinase 3-ANCA or myeloperoxidase-ANCA 3. Severe vasculitis defined by at least one of the following: 3.1. Renal involvement, characterised by: 3.1.1. Renal biopsy demonstrating focal necrotising glomerulonephritis or active urine sediment demonstrating glomerular haematuria/red cell casts and proteinuria, and 3.1.2. Estimated glomerular filtration rate (eGFR) less than 50 ml/min/1.73 m2), or 3.2. Pulmonary haemorrhage due to active vasculitis (defined by a compatible chest x-ray or computed tomography [CT] scan (diffuse pulmonary infiltrates), and 3.3. The absence of an alternative explanation for all pulmonary infiltrates (i.e. volume overload or pulmonary infection), and 3.4. At least one of the following: 3.4.1. Evidence of alveolar haemorrhage on bronchoscopic examination or increasingly bloody returns with bronchoalveolar lavage 3.4.2. Observed haemoptysis 3.4.3. Unexplained anaemia (less than 10 g/dl) or documented drop in haemoglobin (greater than 1 g/dl) 3.4.4. An increased diffusing capacity of carbon dioxide 4. Provision of informed consent by patient or a surrogate decision maker 5. Aged greater than or equal to 15 years, either sex
Exclusion criteria
Exclusion criteria: 1. A diagnosis of vasculitis other than Wegener's granulomatosis or microscopic polyangiitis 2. Positive anti-glomerular basement membrane antibody test or renal biopsy demonstrating linear glomerular immunoglobulin deposition 3. Receipt of dialysis for greater than 21 days immediately prior to randomisation or prior renal transplant 4. Aged less than 15 years (aged less than 18 years at centres that do not treat paediatric patients) 5. Pregnancy 6. Treatment with greater than 1 intravenous (IV) dose of cyclophosphamide and/or greater than 14 days of oral cyclophosphamide and/or greater than 14 days of prednisone/prednisolone (greater than 30 mg/day) and/or greater than 1 dose of rituximab within the 28 days immediately prior to randomisation 7. 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 Added 30/10/2019: 8. Plasma exchange in 3 months prior to randomization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Death or end-stage renal disease. Timepoint for all analyses is the common closeout date (2 years after the last patient is enrolled). | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures, as of 21/03/2018: 1. Sustained remission will be analyzed by comparing the difference in proportions (and associated 95% confidence intervals) of patients that achieve a sustained remission in each treatment group. 2. Death and ESRD will be analyzed separately in an identical manner to the composite primary endpoint. 3. Safety analyses will be performed by assessing the 95% confidence interval of the rate difference of serious adverse events between treatment groups. 4. The rate of serious infections will be assessing the 95% confidence interval of the rate difference between the treatment groups both for the first year and at trial end. 5. Health-related quality of life using the SF-36 Physical Composite, Mental Composite and EQ-5D Index Score. Patients were seen at Week 26, Week 52 and then every 6 months until study end. Previous secondary outcome measures: 1. Disease activity (measured with the Birmingham Vasculitis Activity Score 2003) 2. Health related quality of life (measured with the EuroQoL EQ5D index score and 36-item Short Form Health Survey) 3. Serious adverse events Timepoint for all analyses is the common closeout date (2 years after the last patient is enrolled). | — |
Countries
Australia, Canada, Czech Republic, Denmark, England, France, Germany, Italy, Mexico, Netherlands, New Zealand, Spain, Sweden, Switzerland, United Kingdom, United States of America
Outcome results
None listed