Re-analysis of the PolyHeme Phase III trial dataset: Lessons for future haemoglobin-based oxygen carrier trauma trials

•New analyses of the PolyHeme Phase III clinical trial database examined adverse early outcomes versus original 30-day mortality; amongst 714 trauma patients, adverse event reporting showed coagulopathy was significantly more frequent after PolyHeme administration than blood in the first 12 h; 10 more liters of fluid were administered during initial resuscitation of 55 patients with major haemorrhage randomized to PolyHeme; nadir total haemoglobin [THb] < 6 g/dl was correlated with increased mortality on Day 1 after PolyHeme; future trials should use HBOC with higher haemoglobin concentration, lower volume and transition to blood plus coagulation factors or whole blood. To assist design of future HBOC clinical trials for pre-hospital and prolonged field care, the haemoglobin-based-oxygen carrier (HBOC) Phase III trauma trial database comparing PolyHeme to blood transfusion was re-analysed to identify causes of adverse early outcomes versus the 30-day mortality outcome of the original trial. We questioned if failure of PolyHeme (10 g/dl) to increase haemoglobin concentration and dilutional coagulopathy versus blood, caused higher Day 1 mortality in the PolyHeme arm of the trial. New analyses of the original trial database, including Fisher's exact test, examined impact of interval changes in total haemoglobin [THb], coagulation, fluid volumes administered and mortality on Day 1 in the Control (pre-hospital crystalloids, then blood after trauma centre admission) and PolyHeme arms of the trial. Admission [THb] was significantly greater (p