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

Study Description

Worldwide trauma is 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 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 injury, and anti-inflammatory properties.

In two large multicentre, randomized, 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, ulticentre, randomized, 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, following a prespecified 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 The United States of America, United Kingdom, Canada, Australia and New Zealand.

Management Committee

Craig French (Chair), Rinaldo Bellomo, Jamie Cooper, Lorraine Little (Project Manager), Lena Napolitano, Alistair Nichol, Jeffrey Presneill and Michael Reade.

Administering Institution

ANZIC Research Centre, Monash University

Sample Size

2500 patients

Project Status as of June 2019

Plan to commence recruiting early in 2020.




Craig French (email)