Preclinical work in the Founder’s laboratory and a small, open-label, clinical study in Slovenia, supports a beneficial effect of erythropoietin during CPR leading to better cardiac function after resuscitation with improved survival.
Given the clinical availability of erythropoietin and its known safety profile, erythropoietin has been chosen by Resuscitation Therapeutics to be developed as the first pharmacological intervention to improve outcome by attenuating reperfusion injury during CPR. Erythropoietin, through non-genomic mechanisms, quickly activates inside cells molecular pathways that make mitochondria more resistant to reperfusion injury.
This effect leads to better preservation of cardiac function after resuscitation, greater hemodynamic stability, and improved survival. In addition, some studies suggest that the effect of erythropoietin may manifest during CPR preventing the heart from becoming stiff – an acute manifestation of reperfusion injury – enabling chest compressions during CPR to remain hemodynamically effective for a longer period of time. In the Slovenian study, use of erythropoietin was associated with a dramatic improvement in initial resuscitation from 64% to 92% and in survival from 27% to 54%.
Resuscitation Therapeutics is in the planning stages of phase II clinical trials in the United States with the goals of validating the previous preclinical studies, determine the optimal time window for administration during CPR, and provide an estimate of the treatment effect before conducting a large multicenter clinical trial that would determine the effectiveness and further identify the population of sudden cardiac arrest victims more likely to benefit from erythropoietin given during CPR.