A Randomized Controlled Trial: Regenerative Effects, Efficacy and Safety of Erythropoietin in Burn and Scalding Injuries

Abstract

In adult’s burn injuries belong to the top 15 causes of injury. Annually more than a million patients receive specialized treatment. Improving burned patients’ outcomes is still a challenge. Effects of erythropoietin (EPO) are reported to be pro-angiogenic, pro-regenerative, anti-inflammatory, immunomodulatory and hypoxia/ischemia protective. Study objectives were to demonstrate cytoprotective and regenerative effects of EPO in burned patients in terms of improved wound healing, reduced morbidity and mortality. This was a prospective, placebo-controlled, randomized, double-blind trial. The trial was conducted in 13 specialized burn care centers in Germany. Adult Patients with 2b° or 3° burn injuries were included. Patients received state of the art burn care including obligatory split skin graft transplantation. Study medication was EPO or placebo every other day for 21 days. Between 12/08 and 06/14, 116 patients were randomized, 84 received study medication (EPO 45, Placebo 39). Primary endpoint analysis revealed inconclusive results, as only a minority of patients reached the primary endpoint [100% re-epithelialization: EPO: 23% (9/40); Placebo 30% (11/37)]. Several secondary endpoints such as SOFA score (morbidity), EPO level in blood and wound healing onset revealed clinical, and statistically significant results in favor of the EPO group. Adverse Events (AEs) and Severe Adverse Events (SAEs) were in expected ranges; AEs EPO: 80%, (36/45), Placebo: 77%, (30/39); SAEs EPO: 24%, (11/45), Placebo: 24%, (8/39). Out of 84 patients two died, one per group, thus mortality was lower than expected. Results (SOFA score) indicate a lower morbidity of the EPO group, suggesting pro-regenerative effects of EPO in burned patients. Higher EPO levels might influence the faster onset of re-epithelialization in the first 10 days of the treatment. Both effects could reveal new therapeutic options.Clinical Trial Registration: ISRCT Number: ISRCTN95777824 and EudraCT Number: 2006-002886-38, Protocol Number: 0506.

Relation Between Gender and Concomitant Medications With Erythropoietin-Treatment on Wound Healing in Burn Patients. Post Hoc Subgroup-Analysis of the Randomized, Placebo-Controlled Clinical Trial “EPO in Burns”

“…In the previously published main findings of the "EPO in Burns" study, EPO was found to be safe in severely burned patients. In addition, an organ protecting and stabilizing effect in severely burned patients (SOFA score) and an earlier onset of wound healing in the EPO group was demonstrated (Gunter et al, 2018).…”

“…Thromboembolic events could thus be reduced to ranges seen in poly-traumatized patients not receiving EPO when combined with appropriate anti-thrombotic therapy (Corwin et al, 2007). In our previous publication of "EPO in Burns," we presented primary and secondary endpoint analysis data, including safety, regenerative effects, and efficacy of systemically applied (s.c.) EPO in split skin graft donor sites, as well as in burn and scald injuries, and severely burned patients (Gunter et al, 2018). However, the analysis of the primary endpoint of the "EPO in Burns" study regarding the complete reepithelialization of a defined split skin graft donor site (= the study wound) did not show conclusive results regarding EPO effects on wound healing.…”

Regenerative Properties of Recombinant Human Erythropoietin in the Wound Healing

“…It is noted that the administration of low doses of EPO improves wound healing in patients with diabetes without affecting the hematocrit level [26]. In RCTs, Guenter EPO was used to treat burns [27]. However, the results (epithelialization of burn wounds) were inconclusive.…”

Regenerative properties of recombinant human erythropoetin in wound healing

“…В РКИ К. Guenter ЭПО применяли для лечения ожогов [35]. При этои результаты (эпителизация ожоговых ран) были неубедительными.…”