Condition category
Circulatory System
Date applied
21/09/2005
Date assigned
13/03/2006
Last edited
30/07/2010
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.vasculitis.org

Contact information

Type

Scientific

Primary contact

Dr Jayne David

ORCID ID

Contact details

Box 118
Department of Renal Medicine
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 2QQ
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Acronym

RITUXVAS

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

Ethics approval

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

ANCA associated vasculitis

Intervention

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.

Intervention type

Drug

Phase

Not Specified

Drug names

Rituximab, standard therapy of cyclophosphamide/azathioprine

Primary outcome measures

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 measures

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

Overall trial start date

01/11/2005

Overall trial end date

01/11/2008

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

40

Participant 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

Recruitment start date

01/11/2005

Recruitment end date

01/11/2008

Locations

Countries of recruitment

Australia, Czech Republic, Germany, Mexico, Netherlands, Sweden, Switzerland, United Kingdom

Trial participating centre

Box 118
Cambridge
CB2 2QQ
United Kingdom

Sponsor information

Organisation

Cambridge University Hospitals NHS Foundation Trust (UK)

Sponsor details

Box 146
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 2QQ
United Kingdom

Sponsor type

Government

Website

Funders

Funder type

Industry

Funder name

Research grant provided by Hoffman La Roche to investigator own account - vasculitis research account

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20647198

Publication citations

  1. Results

    Jones RB, Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA, Savage CO, Segelmark M, Tesar V, van Paassen P, Walsh D, Walsh M, Westman K, Jayne DR, , Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis., N. Engl. J. Med., 2010, 363, 3, 211-220, doi: 10.1056/NEJMoa0909169.

Additional files

Editorial Notes