Human Polymerized Hemoglobin for the Treatment of Hemorrhagic Shock when Blood Is Unavailable

The USA Multicenter Trial

Ernest E. Moore, Frederick A. Moore, Timothy Fabian, Andrew C. Bernard, Gerard J. Fulda, David B. Hoyt, Therese M. Duane, Leonard J. Weireter, Gerardo A. Gomez, Mark D. Cipolle, George H. Rodman, Mark A. Malangoni, George A. Hides, Laurel A. Omert, Steven A. Gould

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

Background: Human polymerized hemoglobin (PolyHeme, Northfield Laboratories) is a universally compatible oxygen carrier developed to treat life-threatening anemia. This multicenter phase III trial was the first US study to assess survival of patients resuscitated with a hemoglobin-based oxygen carrier starting at the scene of injury. Study Design: Injured patients with a systolic blood pressure ≤ 90 mmHg were randomized to receive field resuscitation with PolyHeme or crystalloid. Study patients continued to receive up to 6 U of PolyHeme during the first 12 hours postinjury before receiving blood. Control patients received blood on arrival in the trauma center. This trial was conducted as a dual superiority/noninferiority primary end point. Results: Seven hundred fourteen patients were enrolled at 29 urban Level I trauma centers (79% men; mean age 37.1 years). Injury mechanism was blunt trauma in 48%, and median transport time was 26 minutes. There was no significant difference between day 30 mortality in the as-randomized (13.4% PolyHeme versus 9.6% control) or per-protocol (11.1% PolyHeme versus 9.3% control) cohorts. Allogeneic blood use was lower in the PolyHeme group (68% versus 50% in the first 12 hours). The incidence of multiple organ failure was similar (7.4% PolyHeme versus 5.5% control). Adverse events (93% versus 88%; p = 0.04) and serious adverse events (40% versus 35%; p = 0.12), as anticipated, were frequent in the PolyHeme and control groups, respectively. Although myocardial infarction was reported by the investigators more frequently in the PolyHeme group (3% PolyHeme versus 1% control), a blinded committee of experts reviewed records of all enrolled patients and found no discernable difference between groups. Conclusions: Patients resuscitated with PolyHeme, without stored blood for up to 6 U in 12 hours postinjury, had outcomes comparable with those for the standard of care. Although there were more adverse events in the PolyHeme group, the benefit-to-risk ratio of PolyHeme is favorable when blood is needed but not available.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalJournal of the American College of Surgeons
Volume208
Issue number1
DOIs
StatePublished - Jan 1 2009

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Hemorrhagic Shock
Multicenter Studies
Hemoglobins
Therapeutics
Trauma Centers
PolyHeme
Wounds and Injuries
Oxygen
Blood Pressure
Multiple Organ Failure
Standard of Care
Resuscitation
Anemia

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Human Polymerized Hemoglobin for the Treatment of Hemorrhagic Shock when Blood Is Unavailable : The USA Multicenter Trial. / Moore, Ernest E.; Moore, Frederick A.; Fabian, Timothy; Bernard, Andrew C.; Fulda, Gerard J.; Hoyt, David B.; Duane, Therese M.; Weireter, Leonard J.; Gomez, Gerardo A.; Cipolle, Mark D.; Rodman, George H.; Malangoni, Mark A.; Hides, George A.; Omert, Laurel A.; Gould, Steven A.

In: Journal of the American College of Surgeons, Vol. 208, No. 1, 01.01.2009, p. 1-13.

Research output: Contribution to journalArticle

Moore, EE, Moore, FA, Fabian, T, Bernard, AC, Fulda, GJ, Hoyt, DB, Duane, TM, Weireter, LJ, Gomez, GA, Cipolle, MD, Rodman, GH, Malangoni, MA, Hides, GA, Omert, LA & Gould, SA 2009, 'Human Polymerized Hemoglobin for the Treatment of Hemorrhagic Shock when Blood Is Unavailable: The USA Multicenter Trial', Journal of the American College of Surgeons, vol. 208, no. 1, pp. 1-13. https://doi.org/10.1016/j.jamcollsurg.2008.09.023
Moore, Ernest E. ; Moore, Frederick A. ; Fabian, Timothy ; Bernard, Andrew C. ; Fulda, Gerard J. ; Hoyt, David B. ; Duane, Therese M. ; Weireter, Leonard J. ; Gomez, Gerardo A. ; Cipolle, Mark D. ; Rodman, George H. ; Malangoni, Mark A. ; Hides, George A. ; Omert, Laurel A. ; Gould, Steven A. / Human Polymerized Hemoglobin for the Treatment of Hemorrhagic Shock when Blood Is Unavailable : The USA Multicenter Trial. In: Journal of the American College of Surgeons. 2009 ; Vol. 208, No. 1. pp. 1-13.
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abstract = "Background: Human polymerized hemoglobin (PolyHeme, Northfield Laboratories) is a universally compatible oxygen carrier developed to treat life-threatening anemia. This multicenter phase III trial was the first US study to assess survival of patients resuscitated with a hemoglobin-based oxygen carrier starting at the scene of injury. Study Design: Injured patients with a systolic blood pressure ≤ 90 mmHg were randomized to receive field resuscitation with PolyHeme or crystalloid. Study patients continued to receive up to 6 U of PolyHeme during the first 12 hours postinjury before receiving blood. Control patients received blood on arrival in the trauma center. This trial was conducted as a dual superiority/noninferiority primary end point. Results: Seven hundred fourteen patients were enrolled at 29 urban Level I trauma centers (79{\%} men; mean age 37.1 years). Injury mechanism was blunt trauma in 48{\%}, and median transport time was 26 minutes. There was no significant difference between day 30 mortality in the as-randomized (13.4{\%} PolyHeme versus 9.6{\%} control) or per-protocol (11.1{\%} PolyHeme versus 9.3{\%} control) cohorts. Allogeneic blood use was lower in the PolyHeme group (68{\%} versus 50{\%} in the first 12 hours). The incidence of multiple organ failure was similar (7.4{\%} PolyHeme versus 5.5{\%} control). Adverse events (93{\%} versus 88{\%}; p = 0.04) and serious adverse events (40{\%} versus 35{\%}; p = 0.12), as anticipated, were frequent in the PolyHeme and control groups, respectively. Although myocardial infarction was reported by the investigators more frequently in the PolyHeme group (3{\%} PolyHeme versus 1{\%} control), a blinded committee of experts reviewed records of all enrolled patients and found no discernable difference between groups. Conclusions: Patients resuscitated with PolyHeme, without stored blood for up to 6 U in 12 hours postinjury, had outcomes comparable with those for the standard of care. Although there were more adverse events in the PolyHeme group, the benefit-to-risk ratio of PolyHeme is favorable when blood is needed but not available.",
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AU - Bernard, Andrew C.

AU - Fulda, Gerard J.

AU - Hoyt, David B.

AU - Duane, Therese M.

AU - Weireter, Leonard J.

AU - Gomez, Gerardo A.

AU - Cipolle, Mark D.

AU - Rodman, George H.

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AU - Gould, Steven A.

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N2 - Background: Human polymerized hemoglobin (PolyHeme, Northfield Laboratories) is a universally compatible oxygen carrier developed to treat life-threatening anemia. This multicenter phase III trial was the first US study to assess survival of patients resuscitated with a hemoglobin-based oxygen carrier starting at the scene of injury. Study Design: Injured patients with a systolic blood pressure ≤ 90 mmHg were randomized to receive field resuscitation with PolyHeme or crystalloid. Study patients continued to receive up to 6 U of PolyHeme during the first 12 hours postinjury before receiving blood. Control patients received blood on arrival in the trauma center. This trial was conducted as a dual superiority/noninferiority primary end point. Results: Seven hundred fourteen patients were enrolled at 29 urban Level I trauma centers (79% men; mean age 37.1 years). Injury mechanism was blunt trauma in 48%, and median transport time was 26 minutes. There was no significant difference between day 30 mortality in the as-randomized (13.4% PolyHeme versus 9.6% control) or per-protocol (11.1% PolyHeme versus 9.3% control) cohorts. Allogeneic blood use was lower in the PolyHeme group (68% versus 50% in the first 12 hours). The incidence of multiple organ failure was similar (7.4% PolyHeme versus 5.5% control). Adverse events (93% versus 88%; p = 0.04) and serious adverse events (40% versus 35%; p = 0.12), as anticipated, were frequent in the PolyHeme and control groups, respectively. Although myocardial infarction was reported by the investigators more frequently in the PolyHeme group (3% PolyHeme versus 1% control), a blinded committee of experts reviewed records of all enrolled patients and found no discernable difference between groups. Conclusions: Patients resuscitated with PolyHeme, without stored blood for up to 6 U in 12 hours postinjury, had outcomes comparable with those for the standard of care. Although there were more adverse events in the PolyHeme group, the benefit-to-risk ratio of PolyHeme is favorable when blood is needed but not available.

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