HBOC-201 as an alternative to blood transfusion: efficacy and safety evaluation in a multicenter phase III trial in elective orthopedic surgery.
BACKGROUND
The ability of hemoglobin based oxygen carrier-201 (HBOC-201) to safely reduce and/or eliminate perioperative transfusion was studied in orthopedic surgery patients.


METHODS
A randomized, single-blind, packed red blood cell (PRBC)-controlled, parallel-group multicenter study was conducted. Six hundred eighty-eight patients were randomized to treatment with HBOC-201 (H, n = 350) or PRBC (R, n = 338) at the first transfusion decision. Primary endpoints were transfusion avoidance and blinded assessment [Mann-Whitney estimator (MW)] of safety noninferiority. Groups were compared directly and by paired/matching group analyses predicated on a prospectively defined dichotomy [treatment success (HH) vs. failure (HR)] in the H arm and an equivalently defined dichotomy [</=3 (R3-) vs. >3 (R3+) units PRBC] in the R arm, based on need (moderate vs. high) for additional oxygen carrying capacity.


RESULTS
A total of 59.4% of patients in the H arm avoided PRBC transfusion. Adverse events (8.47 vs. 5.88), and serious adverse events (SAEs) (0.35 vs. 0.25) per patient were higher in the H versus R arms (p < 0.001 and p < 0.01) with MW = 0.561 (95 CI 0.528-0.594). HH versus R3- had identical (0.14) serious adverse events/patient and a MW = 0.519 (95% confidence limit 0.481-0.558), whereas the incidence was higher (0.63 vs. 0.47) for HR versus R3+ with a MW = 0.605 (95% confidence limit 0.550-0.662). Age (>80 years), volume overload and undertreatment contributed to this imbalance.


CONCLUSIONS
HBOC-201 eliminated transfusion in the majority of subjects. The between arms (H vs. R) safety analysis was unfavorable and likely related to patient age, volume overload, and undertreatment and was isolated to patients that could not be managed by HBOC-201 alone. However, patients <80 years old with moderate clinical need may safely avoid transfusion when treated with up to 10 units of HBOC-201.
Jahr
Jonathan S
JS
David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Mackenzie
Colin
C
Pearce
L Bruce
LB
Pitman
Arkadiy
A
Greenburg
A Gerson
AG
D000328:Adult; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D001802:Blood Substitutes / Q000008:administration & dosage; D017558:Elective Surgical Procedures; D017707:Erythrocyte Transfusion; D005069:Evaluation Studies as Topic; D005260:Female; D005500:Follow-Up Studies; D006454:Hemoglobins / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019637:Orthopedic Procedures / Q000379:methods*; D011336:Probability; D018570:Risk Assessment; D012449:Safety; D016037:Single-Blind Method; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D001802:Blood Substitutes; D006454:Hemoglobins; C096798:HBOC 201