Traumatic injury is a major public health problem with an extraordinary human, social and economic burden. The World Health Organization forecasts that, by 2030, trauma will become the third leading cause of death and disability globally. In 2015, 1,684 major trauma patients were admitted to hospital in Ireland, the majority of these were young (between 16 and 64) and in the 923 with severe trauma had a mortality rate of 15%.
Erythropoietin (EPO) is a glycoprotein hormone essential for erythropoiesis (red blood cell production), however, EPO has many important protective effects far beyond its erythropoietic effects. These include reducing post-trauma inflammatory tissue damage and facilitating healing and regeneration of multiple tissues and organs.
We hypothesize that the administration of recombinant EPO (epoetin alfa) reduces mortality in critically ill trauma patients six months after injury. To test this hypothesis we propose to conduct a multi-centre, randomised controlled trial evaluating the effect of EPO compared to placebo in critically ill patients following trauma.
In addition to the substantial experimental evidence providing a strong biological rationale, there is supportive evidence from observational and randomized clinical trials to suggest a likely beneficial effect of EPO in critically ill trauma patients. Our previous work has established that the administration of EPO to critically injured trauma patients is safe, feasible and likely to increase survival. Our recent meta-analysis of these trials demonstrated a 37% reduction in mortality of patients who received EPO versus placebo. However, these clinical studies had limitations which have limited their adoption into clinical practice (i.e. trauma patients were retrospectively or prospectively defined subgroups, mortality was a secondary endpoint etc).
Consequently the administration of EPO is not currently the standard of care in Ireland or elsewhere despite some recommendations for its use; however, if proven effective, the administration of EPO to this patient population may save thousands of young lives worldwide each year and result in huge economic, societal and human benefits in Ireland and globally.
This proposed study will formally address this important question and provide much needed guidance to clinicians: What is the role of EPO in critically injured trauma patients?
