Plasma EXchange and glucocorticoids In anti-neutrophil cytoplasm antibody associated systemic VASculitis

Principal Investigator: Dr Chen Au Peh
Project Officer: Andrea Valks (AKTN)
Trial Number: EUDRACT 2009-013220-24

Population: Patients with ANCA-associated vasculitis, as shown by either severe kidney impairment or severe lung haemorrhage.

Intervention: PLEX vs no PLEX in combination with standard dose vs reduced dose glucocorticoids
Follow-up: 1-7 years
Primary outcome: Composite of all-cause mortality or end-stage kidney disease
Status: Trial completed
Recruitment end date: 30 November 2016
Follow-up end date: 31 December 2017
Recruitment: 704/700

Trial Summary
Vasculitis is an inflammation of the small blood vessels in the body leading to a restriction of blood supply to organs and tissues. When the kidneys or lungs are affected, “plasma exchange” can be used as an effective treatment option. It quickly removes an antibody called ANCA (as well as other harmful substances) so that the disease can be controlled and kidneys and/or lungs can recover. The treatment method of plasma exchange combined with drugs (steroids and cyclophosphamide), is effective at controlling the disease but has toxic side effects, particularly infections. It is important to use the correct dose of these drugs in order to balance their benefit with their side effects but unfortunately it is unknown what the correct dose should be.

The PEXIVAS Trial involved patients with ANCA Vasculitis, where the kidneys and/or lungs are affected. They were randomised to either receive plasma exchange or no plasma exchange and a standard dose of steroids or a reduced dose of steroids. The study ran for seven years and the results were expected to reveal the ideal dosage for controlling Vasculitis and in doing so, greatly improve the quality of life of those with Vasculitis.

Trial Results
Key features

  • The largest study into ANCA Vasculitis conducted to date
  • The trial ran from June 2010 through September 2016
  • An international, multi-centre, randomised controlled trial, involving 704 patients at 95 centres across 16 countries, including Australia, New Zealand, Japan and the UK
  • Funded by the UK National Institute for Health Research (NIHR) and several international funders, such as the Australian Government National Health and Medical Research Council (NHMRC)
  • Teams based in Australia and New Zealand recruited 94 and 10 participants respectively across their respective 17 and 4 centres

“This trial demonstrated that we can make a difference by collaborating with international partners. We hope that the PEXIVAS model will set an example for future clinical trials to follow in ANZ.”
 – Dr Chen Au Peh, Consultant Kidney Physician, Royal Adelaide Hospital; Clinical Associate Professor of Medicine, The University of Adelaide.

“PEXIVAS was a very important trial on many fronts. Operationally, it demonstrated how Australia and New Zealand can collaborate effectively and make an important contribution to international trials with our Australasian Kidney Trials Network infrastructure set up for just this purpose.”
 – Professor Carmel Hawley, Senior Staff Specialist and Director of Haemodialysis Services, Princess Alexandra Hospital; Professor, School of Medicine, The University of Queensland; Chair, Australasian Kidney Trials Network (AKTN)

NIHR website quotes:

“PEXIVAS has shown how an international collaboration, with funding from multiple government agencies, can successfully conduct a large rare disease study. The results will be of direct benefit to patients with vasculitis and will reduce healthcare costs.”
Professor David Jayne, Director of the Vasculitis and Lupus Service, Addenbrooke’s Hospital and Professor of Clinical Autoimmunity, University of Cambridge.

“If the trial results are adopted into routine clinical practice, patients will no longer need to endure the inconvenience of plasma exchange, a treatment that offers no added benefit. Using lower doses of steroids is also appealing because of the reduced risk of infection. PEXIVAS has shown how treatment of ANCA associated vasculitis can be made safer and cheaper, thus saving the NHS money.”
Professor David Wheeler, NIHR National Specialty Lead for Kidney Disorders explains the impact of the trial results in the UK.

Outcomes and findings

  • Plasma exchange did not result in lower risk of death or end stage kidney disease compared to no plasma exchange
  • Patients who received a reduced dose of steroids did just as well as those patients who received the standard dose
  • A reduced dose of steroids lowered the risk of serious infections in the first year of treatment

Key benefits for treatment

  • We do not have to use plasma exchange routinely, except perhaps in those patients with severe lung haemorrhage
  • We can safely use fewer steroids, which is good news for patients because it will lead to fewer infections
  • Patients and treatment centres are able to avoid unnecessary and expensive plasma exchange

Key publications

Read the full publications via the link.  Click here to read the Main results paper