PMID- 19204509
OWN - NLM
STAT- MEDLINE
DCOM- 20090428
LR  - 20181201
IS  - 1529-8809 (Electronic)
IS  - 0022-5282 (Linking)
VI  - 66
IP  - 2
DP  - 2009 Feb
TI  - HBOC-201 vasoactivity in a phase III clinical trial in orthopedic surgery 
      subjects--extrapolation of potential risk for acute trauma trials.
PG  - 365-76
LID - 10.1097/TA.0b013e3181820d5c [doi]
AB  - BACKGROUND: Vasoactivity has hampered progress of hemoglobin-based oxygen 
      carriers (HBOCs) due to concern for adverse blood pressure responses and 
      secondary complications. A recent formulation, highly polymerized HBOC-201 
      (Biopure, Cambridge, MA), has been found to be less vasoactive than prior less 
      polymerized formulations, and to improve outcome in animal models of hemorrhagic 
      shock (HS) compared with standard resuscitation fluids. HBOCs are envisioned to 
      have life- saving potential for severe trauma patients for whom death due to HS 
      is common despite transport to level I trauma centers. As part of a benefit:risk 
      analysis for a proposed clinical trial of HBOC-201 in patients with traumatic HS, 
      we analyzed data from a previous phase III clinical trial of this HBOC that 
      involved orthopedic surgery patients, for vasoactivity and related effects, with 
      focus on patients more representative of the trauma population. STUDY DESIGN: In 
      a previous phase III study involving orthopedic surgery patients, HEM-0115, 
      consented/stabilized patients were randomized to receive HBOC-201 (N = 350) (up 
      to ten 30 g Hb units) or red blood cells (RBC) (N = 338) (up to 9 units) at the 
      first transfusion decision. Systolic blood pressure (SBP) responses, key system 
      and individual adverse events (AEs) and serious adverse events, and cardiac 
      biomarker elevation incidences, were compared in the overall population and 
      subpopulations with stable trauma, hypotension, and with age stratification 
      (Student's t and Fisher's exact tests, significance p < 0.05). RESULTS: Mild to 
      moderate peak SBP responses were common in HBOC-201 subjects and more common than 
      with RBC in the overall population (mean, 60.8 years old), but less frequent in 
      HBOC-201 subjects with stable trauma, younger age (<50 years old), and 
      hypotension, in whom group differences were narrowed. SBP Delta responses were 
      more common with HBOC-201 than RBC in the overall population, but not in subjects 
      with stable trauma and <50 year olds, in whom response rates were lower. In the 
      overall population, AEs were more common than with RBC in most systems (also, 
      hypertension and stroke); only cardiac system serious adverse events were more 
      common with HBOC-201. In contrast, there were few significant group differences 
      in stable trauma, hypotensive, and <70 and especially <50-year-old subjects, in 
      whom AE incidences were generally lower. A disproportionate number of key AEs 
      occurred in elderly subjects. Troponin (but not CK-MB) elevation was more 
      frequent with HBOC-201 than RBC in the overall population but not in <50 year 
      olds, and was not associated with acute coronary syndrome (ACS) or death. 
      CONCLUSIONS: Our limited HEM-0115 safety analysis shows that key potentially 
      vasoactivity-related adverse safety signals were more frequent with HBOC-201 than 
      RBC in older patients undergoing orthopedic surgery with rapid access to safe 
      blood transfusions. That incidences of these safety signals were generally lower 
      and group differences narrowed in subpopulations with stable trauma, hypotension, 
      and younger age, suggests an acceptable safety profile in younger acute trauma 
      populations, especially in settings where rapid access to safe blood transfusions 
      is unavailable; confirmation in controlled clinical trials is urgently warranted.
FAU - Freilich, Daniel
AU  - Freilich D
AD  - Hematomimetics Program, Trauma and Resuscitative Medicine Department, Naval 
      Medical Research Center, Silver Spring, Maryland, USA. 
      daniel.freilich@med.navy.mil
FAU - Pearce, L Bruce
AU  - Pearce LB
FAU - Pitman, Arkadiy
AU  - Pitman A
FAU - Greenburg, Gerson
AU  - Greenburg G
FAU - Berzins, Mara
AU  - Berzins M
FAU - Bebris, Lolita
AU  - Bebris L
FAU - Ahlers, Steven
AU  - Ahlers S
FAU - McCarron, Richard
AU  - McCarron R
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Trauma
JT  - The Journal of trauma
JID - 0376373
RN  - 0 (Blood Substitutes)
RN  - 0 (Hemoglobins)
RN  - 1XQE66T19H (HBOC 201)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Blood Substitutes/adverse effects/*pharmacology
MH  - Clinical Trials as Topic
MH  - Erythrocyte Transfusion/adverse effects/*statistics & numerical data
MH  - Female
MH  - Hemoglobins/adverse effects/*pharmacology
MH  - Humans
MH  - Linear Models
MH  - Male
MH  - Middle Aged
MH  - *Orthopedics
MH  - Risk
MH  - Single-Blind Method
EDAT- 2009/02/11 09:00
MHDA- 2009/04/29 09:00
CRDT- 2009/02/11 09:00
PHST- 2009/02/11 09:00 [entrez]
PHST- 2009/02/11 09:00 [pubmed]
PHST- 2009/04/29 09:00 [medline]
AID - 00005373-200902000-00011 [pii]
AID - 10.1097/TA.0b013e3181820d5c [doi]
PST - ppublish
SO  - J Trauma. 2009 Feb;66(2):365-76. doi: 10.1097/TA.0b013e3181820d5c.