First results on regenerative effects of erythropoietin in burn and scald injures (clinical trial: “EPO in Burns”)

Introduction: Large 3° and deep 2° thermal injuries are life threatening and wound surfaces need quick coverage by split skin grafts following tangential or epifascial necrectomy. Initially, it was assumed that EPO was only a hormone affecting erythropoiesis, it has now been demonstrated, that EPO plays a key role in its reaction to acute and chronic tissue damage. Furthermore, EPO has a significant anti-inflammatory effect, thus EPO enhances healing and “restitutio ad integrum” after trauma. To address the clinical need for regenerative tools after thermal injury we stared to examine the effects of systemic EPO application in severely burned patients. Methods:This trial is a randomized, controlled, double-blinded, national multicenter trial. Patients of both sexes, aged 18 - 75 years can be included. Primer efficiency point is the complete reepithelialisation of a defined split skin graft donor area. We will examine cellular and molecular regenerative effects, stem cell recruitment, DNA and mRNA expression, [EPO] receptor up-regulation, protein expression, quality of scar formation, quality of life, gender differences, and organ dysfunction parameters, number of transfused packed red cells units, adverse events and serious adverse events. Preliminary results: The trial is still in its recruitment phase. Total number of includes patients is 105. So far only 15% of the patients developed SAE's, which is a low number regarding the severity of the injuries (up to ABSI 12). During the preclinical phase of the trial we examined cell cultures and animal models, these showed: After thermal trauma, mice receiving systemic or local EPO, exhibited clearly improved and faster reepithelialization and faster wound healing as compared to control groups. In culture, under hypoxic conditions the addition of IL-6 decreases cell proliferation, if EPO is adjoined the proliferation increases significantly. Conclusion: The trial is still blinded; definite results can only be presented after unblinding. The results from the cell cultures and animal models and the low number of SAE's in the trial leads to the assumption, that EPO might represent a new, effective therapeutic opportunity in the treatment of dermal thermal injuries.