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| [ Print-friendly version ] |
| An international, randomised, open label trial comparing a rituximab-based regimen with a standard cyclophosphamide/azathioprine based regimen in the treatment of active, generalised anti-neutrophilic cytoplasmic antibodies associated vasculitis |
| ISRCTN | ISRCTN28528813 |
| ClinicalTrials.gov identifier | |
| Public title | An international, randomised, open label trial comparing a rituximab-based regimen with a standard cyclophosphamide/azathioprine based regimen in the treatment of active, generalised anti-neutrophilic cytoplasmic antibodies associated vasculitis |
| Scientific title | |
| Acronym | RITUXVAS |
| Serial number at source | N/A |
| Study hypothesis | Rituximab leads to a higher rate of sustained remission compared to standard therapies (cyclophosphamide/azathioprine) with a lower rate of severe adverse events and reduced cyclophosphamide exposure |
| Lay summary | |
| Ethics approval | Not provided at time of registration |
| Study design | Randomised controlled trial |
| Countries of recruitment | Australia, Czech Republic, Germany, Mexico, Netherlands, Sweden, Switzerland, United Kingdom |
| Disease/condition/study domain | ANCA associated vasculitis |
| Participants - 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 |
| Participants - 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 |
| Anticipated start date | 01/11/2005 |
| Anticipated end date | 01/11/2008 |
| Status of trial | Completed |
| Patient information material | |
| Target number of participants | 40 |
| 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 third rituximab dose 2. Control (cyclophosphamide/azathioprine) regimen: cyclophosphamide 15 mg/kg for 3-6 months (6-10 doses total) to be given intravenously according to protocol for remission induction. Cyclophosphamide should be converted to azathioprine for remission maintenance. 3. Steroids: all patients will receive 1 g IV methylprednisolone, then same daily oral corticosteroid regimen 4. Plasma exchange or IV methylprednisolone will be allowed according to local practice for patients with organ threatening disease. Randomisation should not occur until completion of plasma exchange to avoid loss of rituximab during plasma exchange. The first dose of cyclophosphamide can be given prior to completion of plasma exchange. |
| Primary outcome measure(s) |
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 outcome measure(s) |
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 |
| Sources of funding | Research grant provided by Hoffman La Roche to investigator own account - vasculitis research account |
| Trial website | http://www.vasculitis.org |
| Publications | 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20647198 |
| Contact name | Dr Jayne David |
| Address |
Box 118
Department of Renal Medicine Addenbrooke's Hospital Hills Road |
| City/town | Cambridge |
| Zip/Postcode | CB2 2QQ |
| Country | United Kingdom |
| Sponsor | Cambridge University Hospitals NHS Foundation Trust (UK) |
| Address |
Box 146
Addenbrooke's Hospital Hills Road |
| City/town | Cambridge |
| Zip/Postcode | CB2 2QQ |
| Country | United Kingdom |
| Date applied | 21/09/2005 |
| Last edited | 30/07/2010 |
| Date ISRCTN assigned | 13/03/2006 |
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| © 2012 ISRCTN unless otherwise stated. | |
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