A hemoglobin-based oxygen carrier (HBOC-201, Biopure Corporation) appears to be a safe substitute for blood transfusion, according to results of a multinational, phase III clinical trial among patients undergoing elective orthopedic surgery. However, the blood substitute may not be appropriate for high-risk patients and patients over the age of 80, the findings suggest.
As described in the June issue of the Journal of Trauma, "HBOC-201 is a purified cell-free, glutaraldehyde cross-linked and polymerized bovine hemoglobin in a modified lactated Ringer's solution." The authors note that HBOC-201 can be stored at room temperature for up to 3 years and does not require cross matching.
The clinical trial included 688 adults undergoing nonemergency orthopedic surgery at study sites in North America, Europe, and South Africa. Average patient age was 60.8 years; 57 were more than 80 years old.
Patients were randomized to HBOC-201 (n = 350) or packed red blood cells (PRBCs, n = 338) at the point where a transfusion was deemed necessary. Patients received up to 10 units of the blood substitute during 6 days post-surgery; beyond this point, patients requiring further transfusion were switched to PRBCs.
HBOC-201 eliminated the need for blood transfusion in 59% of subjects, lead author Dr. Jonathan S. Jahr, at the David Geffen School of Medicine at UCLA in Los Angeles, and his colleagues report.
However, there were significantly more adverse events, serious adverse events, and adverse events per patient in the HBOC arm of the trial.
An independent review showed that most adverse outcomes involved cardiac and central nervous system events, "likely related to patient age, volume overload, and undertreatment and was isolated to patients that could not be managed by HBOC-201 alone," the report indicates.
Mortality rates did not differ significantly between groups. There were 10 deaths in the HBOC-201 group and six in the PRBC group, none of which the independent reviewers categorized as treatment-related.
Dr. Jahr's team concludes that for patients less than 80 years of age and for whom the predicted need for transfusion is no more than three units of PRBCs, HBOC-201 is a safe alternative. When the estimated need is higher, they recommend that "bridging oxygen delivery needs with HBOC-201 should be considered until blood becomes available."
Furthermore, the researchers advise, "When any form of RBC is not an option, treatment with HBOC-201 is appropriate and may be optimal."
J Trauma 2008;64:1484-1497.
Reviewed by Ramaz Mitaishvili, MD
