Condition category
Mental and Behavioural Disorders
Date applied
01/06/2009
Date assigned
22/06/2009
Last edited
04/08/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Severe, antineutrophil cytoplasm antibody associated vasculitis (AAV) is an uncommon disease of the immune system diagnosed in about 1430 per 100,000 people in the UK each year. It is caused by caused by abnormal antibodies that attack the body’s own cells and tissues. AAV is important because it carries a poor prognosis, with up to half of patients dying or developing kidney failure within 5 years. Two major problems hinder the treatment of AAV: a lack of treatment strategies to bring the disease under control quickly before it causes major organ damage, and a high degree of treatment-related toxicity (side effects). The aim of this study is to examine these problems in patients with severe AAV.

Who can participate?
Patients aged 15 or over with severe AAV

What does the study involve?
Participants are randomly allocated to either receive plasma exchange (a method of rapidly removing the abnormal antibodies), or to not receive plasma exchange. Participants are also randomly allocated to receive either a standard dose of steroids or a low-dose scheme which is predicted to reduce treatment-related toxicity.

What are the possible benefits and risks of participating?
By addressing these problems we hope to significantly improve patient survival and reduce the frequency of kidney failure in patients with AAV.

Where is the study run from?
Addenbrooke's Hospital (UK)

When is the study starting and how long is it expected to run for?
November 2009 to November 2016

Who is funding the study?
Health Technology Assessment Programme (UK)

Who is the main contact?
Dr David Jayne
dj106@cam.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr David Jayne

ORCID ID

Contact details

Addenbrooke's Hospital
Cambridge University Hospitals NHS Foundation Trust
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 586 796
dj106@cam.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00987389

Protocol/serial number

HTA 08/56/04; PEXIVASv1.0

Study information

Scientific title

Plasma exchange and glucocorticoid dosing in the treatment of antineutrophil cytoplasm antibody associated vasculitis: an international randomised controlled trial

Acronym

PEXIVAS

Study hypothesis

This is a two-by-two factorial design randomised controlled trial and has two primary hypotheses:
1. Plasma exchange in addition to immunosuppressive therapy and glucocorticoids will reduce death and end-stage renal disease (ESRD) compared to immunosuppression and glucocorticoids alone in patients with antineutrophil cytoplasm antibody (ANCA) associated vasculitis
2. A reduced dose glucocorticoids regimen will be non-inferior to a standard regimen with respect to death and ESRD in patients with ANCA associated vasculitis

More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/085604
Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0011/53012/PRO-08-56-04.pdf

Ethics approval

Ethics Board: NRES Committee London – Harrow, 30/10/2009, Ref: 09/H0709/56

Study design

Two-by-two factorial design randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Anti-neutrophil cytoplasm antibody associated vasculitis (AAV) with nephritis or lung haemorrhage

Intervention

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 reduced dose glucocorticoid tapering regimen compared to a standard dose glucocorticoid tapering regimen

Intervention type

Mixed

Phase

Drug names

Primary outcome measures

Death or end-stage renal disease. Timepoint for all analyses is the common closeout date (2 years after the last patient is enrolled).

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).

Overall trial start date

01/11/2009

Overall trial end date

01/11/2016

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

500

Participant 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

Recruitment start date

01/06/2010

Recruitment end date

01/11/2016

Locations

Countries of recruitment

Australia, Canada, Czech Republic, Denmark, France, Germany, Italy, Mexico, Netherlands, New Zealand, Spain, Sweden, Switzerland, United Kingdom, United States of America

Trial participating centre

Addenbrooke's Hospital
Cambridge
CB2 0QQ
United Kingdom

Sponsor information

Organisation

Cambridge University Hospitals NHS Foundation Trust (UK)

Sponsor details

Box 277
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 596377
julie.uttridge@addenbrookes.nhs.uk

Sponsor type

Government

Website

http://www.cuh.org.uk/research/research_contacts.html

Funders

Funder type

Government

Funder name

Health Technology Assessment Programme

Alternative name(s)

NIHR Health Technology Assessment Programme, HTA

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Funder name

Medical Research Council (MRC) (UK) (ref: 86772)

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

Food and Drug Administration (USA) and National Institutes of Health (USA) (ref: 1 R01 FD003516-01)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

01/12/2017

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2013 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/23497590

Publication citations

  1. Protocol

    Walsh M, Merkel PA, Peh CA, Szpirt W, Guillevin L, Pusey CD, De Zoysa J, Ives N, Clark WF, Quillen K, Winters JL, Wheatley K, Jayne D, , Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial., Trials, 2013, 14, 73, doi: 10.1186/1745-6215-14-73.

Additional files

Editorial Notes

07/07/2016: Plain English summary added.