MEGASCORES

Sepsis occurs when there is an excessive immune and inflammatory response to an infection. One in five of all global deaths are due to sepsis and there is currently no treatment to reverse sepsis-induced multi-organ failure. Our group has demonstrated that a mega-dose of sodium ascorbate, a sodium salt of vitamin C, can rapidly reverse multi-organ failure in septic sheep without the adverse effects linked with ascorbic acid.

In collaboration with scientific and clinical teams, the Mega-dose ascorbate for sepsis (MEGASCORES) project will investigate physiological, immunological and molecular mechanisms of sodium ascorbate and advance this therapy to Phase Ib and Phase II clinical trials across mainland Australia.

Through this collaboration with leading medical research institutes and public research-intensive intensive care units, the MEGASCORES group aims to transform management of patients with sepsis globally.

Aims

  • Test the safety and feasibility of sodium ascorbate in septic ICU patients.
  • Establish the physiological, molecular and immunological mechanisms of mega-dose sodium ascorbate in sheep, mouse and rat models of sepsis.
  • Determine the optimal dosage of sodium ascorbate for septic humans.
  • Characterise metabolomic, proteomic and biochemical responses following the optimal dosage in septic humans.
  • Carry out a double-blinded, randomised, placebo-controlled trial of mega-dose sodium ascorbate in sepsis across Victoria, New South Wales, South Australia, Western Australia, Queensland and Northern Territory.

Using our unique sheep model of sepsis, which has a very similar phenotype to humans, our group recently showed that a mega-dose of sodium ascorbate could reverse multi-organ failure without the adverse effects linked with ascorbic acid.

We have recently completed a Phase Ia double-blind randomised control trial in 30 septic patients at Austin Health to demonstrate feasibility and physiological signals of benefit of using mega-dose sodium ascorbate. We’ve partnered with leading intensive care clinician-academics and are in the ideal position to enact a research chain from bench-to-bedside.

Research team

Students

Rachel Peiris – PhD

Collaborators

  • Professor Rinaldo Bellomo – Austin Health
  • Dr Mark Plummer – Royal Adelaide Hospital
  • Dr Laura Cook – Peter Doherty Institute
  • Professor Antoine Roquilly – Peter Doherty Institute
  • Dr Neil Glassford – Monash Health
  • Dr Shu Wen – Monash University
  • Dr Alexander Wood – Sir Charles Gairdner Hospital, University of Western Australia
  • Dr Samantha Emery – WEHI

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