ANZICS CTG Endorsed Study
A prospective, multicentre, randomised, doubleblind placebo controlled, stratified phase III trial of epoetin alfa vs. placebo in critically ill trauma patients
Worldwide trauma is a major cause of mortality and long-term morbidity. The World Health Organization has forecast that, by 2030, trauma will become the third leading cause of disability and death globally. Erythropoietin is a glycoprotein hormone essential for erythropoiesis that was first purified in 1977. Its human recombinant analogues are known as erythropoiesis stimulating agents (ESAs) are approved for human therapeutic use.
However, erythropoietin is also a pleiotropic cytokine with effects beyond erythropoiesis. Studies in animals have demonstrated its potential protective effects of erythropoietin to organs including the brain, kidney, liver and heart, and anti-inflammatory properties.
In two large multicentre, randomised, controlled trials, Corwin and colleagues evaluated the use of the ESA epoetin alfa as a red blood cell transfusion sparing agent in critically ill patients. A post hoc pooled analysis of these two trials demonstrated lower mortality in the critically ill trauma patient.
The recent Erythropoietin in Traumatic Brain Injury Study (EPO-TBI) was an international, multicentre, randomised, double-blind, placebo-controlled trial that compared the effect of epoetin alfa, administered within 24 hours of traumatic brain injury, with placebo on patient-centred outcomes. This study demonstrated, that following a pre-specified sensitivity analysis, a significant reduction in six-month mortality. A meta-analysis with trial sequential analysis of all relevant randomised controlled trials evaluating ESAs critically ill trauma patients demonstrated they reduced mortality by at least 20%. This finding may have important implications for patient management.
We therefore plan to conduct a trial of the ESA epoetin alfa in critically ill trauma patients in Australia, New Zealand, Europe, and Saudi Arabia.
Craig French (Co-Chair), Alistair Nichol (Co-Chair), Yasmine Ali Abdelhamid, Yaseen Arabi, Ann-Marie Baker, Deborah Barge, Rinaldo Bellomo, Jamie Cooper, Dashiell Gantner, Matthias Haenggi, Lisa Higgins, Carol Hodgson, Sally Hurford (NZ Project Manager), Sian Donnelly (EU Project Manager), Colin McArthur, Vicki Papanikolaou (Project Manager), Michael Reade, Markus Skrifvars, Tony Trapani
ANZIC Research Centre, Monash University
MRFF, Health Research Board (Ireland), Health Research Council of New Zealand, University Hospital Bern
Craig French (email)
Vicki Papanikolaou (email)