Because total hemoglobin in circulation ([THb]) is an established predictor of clinical outcomes in anemic individuals, the relative efficacies of resuscitation fluids to increase [THb] can be used to design better hemoglobin-based oxygen carrier (HBOC) clinical trials.Methods:
Expected efficacies of HBOC-201 (13 g Hb/dL) and packed RBCs (pRBCs, 24 g Hb/dL) to increase [THb] were calculated and interpreted in the context of SAEs in the HEM-0115 phase III clinical trial.Methods:
The PolyHeme phase III clinical trial compared the HBOC, PolyHeme (10 g Hb/dL), to crystalloid control prehospital and packed RBCs in hospital. The comparative abilities of these resuscitation fluids to maintain [THb] were interpreted in the context of mortality.Results:
In HEM-0115, infusion of HBOC-201 increased [THb] by 0.18 ± 0.03 g/dL (N=121) compared to 0.87 ± 0.07 g/dL (N = 115) following one unit of pRBCs. These observed increases in [THb] were similar to expected increases for these fluids. Use of HBOC-201 was associated with 0.34 SAEs per patient compared to 0.25 SAEs per patient in the pRBC arm (p = 0.016).Results:
Hemoglobin (Hb) Deficit was greater in HBOC-201-treated patients than in pRBC controls and emerged as a predictor of SAEs in a logistics model. Randomization to HBOC-201 had no power to predict SAEs.Results:
PolyHeme more effectively maintained [THb] than did crystalloid prior to arrival at hospital, associated with initially higher survival in the PolyHeme arm. Thereafter, PolyHeme subjects sustained lower [THb] and higher mortality than controls.Conclusion:
Greater anemia in subjects randomized to HBOC-201 was consistent with the relative efficacies of HBOC-201 and pRBCs to increase [THb] and may have contributed to more SAEs in the HBOC arm of HEM-0115 and greater long-term mortality in the PolyHeme trial.