nach oben

Erschienen in:

2013 | OriginalPaper | Buchkapitel

30. Some Critical Comments on the Major HBOC Clinical Trials

verfasst von : George P. Biro

Erschienen in: Hemoglobin-Based Oxygen Carriers as Red Cell Substitutes and Oxygen Therapeutics

Verlag: Springer Berlin Heidelberg

Einloggen

Aktivieren Sie unsere intelligente Suche, um passende Fachinhalte oder Patente zu finden.

search-config

KI-gestützte Suche

Aus

Abstract

From the author’s experience in the HBOC field of basic sciences and commercial product development some critical comments are offered on some of the negative aspects of the major human clinical trials. In particular in trials conducted in the emergency trauma setting the flaws in the execution of the trials have seriously affected the achievement of both efficacy and safety endpoints. In elective surgery trials the safety profile of the HBOC products has been the principal negative outcome. It is proposed that reducing unintentional bias is important and it be accomplished by achieving a balanced subject profile of the trial arms.

Sie haben noch keine Lizenz? Dann Informieren Sie sich jetzt über unsere Produkte:

Springer Professional "Wirtschaft+Technik"

Online-Abonnement

Mit Springer Professional "Wirtschaft+Technik" erhalten Sie Zugriff auf:

über 102.000 Bücher
über 537 Zeitschriften

aus folgenden Fachgebieten:

Automobil + Motoren
Bauwesen + Immobilien
Business IT + Informatik
Elektrotechnik + Elektronik
Energie + Nachhaltigkeit
Finance + Banking
Management + Führung
Marketing + Vertrieb
Maschinenbau + Werkstoffe
Versicherung + Risiko

Jetzt Wissensvorsprung sichern!

Jetzt informieren

Springer Professional "Technik"

Online-Abonnement

Mit Springer Professional "Technik" erhalten Sie Zugriff auf:

über 67.000 Bücher
über 390 Zeitschriften

aus folgenden Fachgebieten:

Automobil + Motoren
Bauwesen + Immobilien
Business IT + Informatik
Elektrotechnik + Elektronik
Energie + Nachhaltigkeit
Maschinenbau + Werkstoffe

Jetzt Wissensvorsprung sichern!

Jetzt informieren

Vorheriges Kapitel Key Adverse Events in Recent HBOC Phase III Clinical Trials and Their Causal Relationship to Test HBOC’s

Nächstes Kapitel Compassionate Use Cases Treated with Hemoglobin-Based Oxygen Carriers

The author was not provided access to the report on this exercise by TheraPure Corp the corporate successor of Hemosol Inc.

The “deviations” should actually be characterized as protocol violations in those cases that involved failure to satisfy exclusion/inclusion criteria.

Alpert J, Thygesen K et al (2000) Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 36:959–969CrossRef

Anderson J, Adams C et al (2007) ACC AHA task force on practice guidelines. J Am Coll Cardiol 50:e1–e157CrossRef

Bennett-Guerrero E, Veldman T et al (2007) Evolution of adverse changes in stored red cells. PNAS 104:17063–17068CrossRef

Bernard A, Moore E et al (2011) Postinjury resuscitation with human polymerized hemoglobin prolongs early survival: a post hoc analysis. J Trauma 70(5):S34–S37CrossRef

Biro G (2012) Adverse HBOC-endothelial dysfunction synergism: a possible contributor to adverse clinical outcomes. Curr Drug Discov Technol 9:194–203CrossRef

Bloomfield E, Rady M et al (2004) A prospective trial of diaspirin cross-linked hemoglobin solution in patients after elective repair of abdominal aortic aneurysm. Mil Med 169:546–550

Bonaventura J (2007) Clinical implications of the loss of vasoactive nitric oxide during red blood cell storage. PNAS 104(49):19165–19166CrossRef

Bonaventura J, Gow A (2004) NO and superoxide: opposite ends of the seesaw in cardiac contractility. PNAS 101(47):16403–16404CrossRef

Chen J-Y, Scerbo M et al (2009) A review of blood substitutes: examining the history, clinical trial results, and ethics of hemoglobin-based oxygen carriers. Clinics 64:803–813CrossRef

Curry N, Hopewell S et al (2011) The acute management of trauma hemorrhage: a systematic review of randomized controlled trials. Crit Care 15:R92–R102CrossRef

Daubert M, Jeremias A (2010) The utility of troponin measurement to detect myocardial infarction: review of the current findings. Vasc Health Risk Manage 6:691–699

Eagle K, Lim M et al (2004) A validated prediction model for all forms of coronary syndrome. JAMA 291:2727–2733CrossRef

Elmer J, Alam H et al (2012) Hemoglobin-based oxygen carriers for hemorrhagic shock. Resuscitation 83:285–292CrossRef

Freilich D, Pearce L et al (2009) HBOC-201 Vasoactivity in a Phase III clinical trial in orthopedic surgery subjects-extrapolation of potential risk for acute trauma trials. J Trauma 66:365–376CrossRef

Gould S, Moore E et al (1998) The first randomized trial of human polymerized hemoglobin as a blood substitute in acute trauma and emergent surgery. J Am Coll Surg 187:113–122CrossRef

Greenburg A, Kim H (2004) Hemglobin-based oxygen carriers. Crit Care 8(Suppl 2):S61–S64CrossRef

Greenburg A, Kim H et al (2004) Use of an oxygen therapeutic as an adjunct to intraoperative autologous donation to reduce transfusion requirements in patients undergoing coronary artery bypass graft surgery. J Am Coll Surg 198:373–383CrossRef

Greenburg A, Pitman A et al (2008) Clinical contextualization and the assessment of adverse events in HBOC trials. Art Cells, Blood Subs, Biotechnol 36:477–486CrossRef

Grimshaw K, Sahler J et al (2011) New frontiers in transfusion biology: identification and significance of mediators of morbidity and mortality in stored red cells. Transfusion 51:874--880

Hausenloy D, Yellon D (2012) Taking lizard saliva to heart. Eur Heart J 33:1426–1430CrossRef

Hill S, Gottschalk L et al (2002) Safety and preliminary efficacy of hemoglobin raffimer for patients undergoing coronary artery bypass surgery. J Cardiothorac Vasc Anesthesia 16:695–702CrossRef

Jahr J, Mackenzie C et al (2008) HBOC-201 as an alternative to blood transfusion: efficacy and safety evaluation in a multicenter Phase III trial in elective orthopedic surgery. J Trauma 64:1484–1497CrossRef

Jevning R, Anand R et al (1994) Certainty and uncertainty in science: the subjectivist concept of probability in physiology and medicine. Am J Physiol 267 (Adv Physiol Educ 12):S113–S119

Kasper S-M, Grune F et al (1998) The effects of increased doses of bovine hemoglobin on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery. Anesth Analg 87:284–291

Kerner T, Ahlers O et al (2003) DCL-Hb for tauma patients with severe hemorrhagic shock: the European “On-Scene” Multicenter Study. Intensive Care Med 29:378–385

Kim-Shapiro DB, Lee J et al (2011) Storage lesion: role in red cell breakdown. Transfusion 51:844--851

Kingma J, Simard D et al (2011) Modulation of nitric oxide affects myocardial perfusion-contraction matching in anaesthetized dogs with recurrent no-flow ischaemia. Exp Physiol 96:1293–1301CrossRef

LaMuraglia G, O’Hara P et al (2000) The reduction of the allogeneic transfusion requirement in aortic surgery with a hemoglobin-based solution. J Vasc Surg 31:299–308CrossRef

Lamy M, Daily E et al (2000) Randomized trail of diaspirin cross-linked hemoglobin solution as an alternative to blood transfusion after cardiac surgery. Anesthesiology 92:646–656CrossRef

Levy J (2011) Hemoglobin-based oxygen carriers for reversing hypotension and shock; “NO” way, “NO” how. Anesthesiology 114:1016–1018CrossRef

Levy J, Goodnough L et al (2002) Polymerized bovine hemoglobin solution as a replacement for allogeneic red blood cell transfusion after cardiac surgery: results of a randomized, double-blind trial. J Thorac Cardiovasc Surg 124:35–42CrossRef

Mackenzie C, Moon-Massat P et al (2010) When blood is not an option: factors affecting survival after the use of a hemoglobin-based oxygen carrier in 54 patients with life threatening anemia. Anesth Analg 110:685–693CrossRef

Meier J, Muller M et al (2011) Perioperative red blood cell transfusion: harmful or beneficial to the patient? Transfus Med Hemother 39:98–103CrossRef

Moore E (2004) Invited Commentary to Greenburg et al. 2004. J Am Coll Surg 198:384–385CrossRef

Moore E, Johnson J et al (2005) Insights from studies of blood substitutes in trauma. Shock 24:197–205CrossRef

Moore E, Cheng A et al (2006) Hemoglobin-based oxygen carriers in trauma care: scientific rationale for the US multicenter prehospital trial. World J Surg 30:1247–1257CrossRef

Moore E, Moore F et al (2009) Human polymerized hemoglobin for the treatment of hemorrhagic shock when blood is not available. J Am Coll Surg 208:1–13CrossRef

Nalysnyk L, Fahrbach K et al (2003) Adverse events in coronary artery bypass grafting (CABG) trials: a systematic review and analysis. Heart 89:767–772CrossRef

Olofson C, Gorecky A et al (2011) Evaluation of MP4OX for prevention of perioperative hypotension in patients undergoing primary hip arthroplasty with spinal anesthesia. Anesthesiology 114:1048–1063CrossRef

Pape A, Stein P et al (2009) Clinical evidence of transfusion effectiveness. Blood Transf 7:250–258

Pattakos G, Koch C et al (2012) Outcome of patients who refuse transfusion after cardiac surgery—a natural experiment with severe blood conservation. Arch Intern Med 172:1154–1160

Rogers M, Blumberg N et al (2009) Hospital variation in transfusion and infection after cardiac surgery: a cohort study. BMC Med 7:37–46CrossRef

Schubert A, Przybelski R et al (2003) Diaspirin-crosslinked hemoglobin reduces blood transfusion in noncardiac surgery: a multicenter, randomized, double-blinded trial. Anesth Analg 97:323–332CrossRef

Silverman T, Weiskopf R (2009) Hemoglobin-based oxygen carriers: current status and future directions. Transfusion 49:2495–2515CrossRef

Sloan E (2003) The clinical trials of diaspirin cross-linked hemoglobin (DCLHb) in severe traumatic hemorrhagic shock: the tale of two continents. Intensive Care Med 29:347–349

Sloan E, Koenigsberg M et al (1999a) Diaspirin cross-linked hemoglobin (DCLHb) in the treatment of severe traumatic hemorrhagic shock. JAMA 282(19):1857–1864CrossRef

Sloan E, Koenigsberg M et al (1999b) Diaspirin cross-linked hemoglobin (DCLHb) in the treatment of severe traumatic hemorrhagic shock. A randomized controlled efficacy trial. JAMA 282:1857–1864CrossRef

Sprung J, Kindscher J et al (2002) The use of bovine hemoglobin glutamer-250 (HemoPure®) in surgical patients: results of a multicenter, randomized, single-blinded trial. Anesth Analg 94:799–808CrossRef

Tinmouth A, Fergusson D et al (2006) Clinical consequences of red cell storage in the critically ill. Transfusion 46:2014–2027CrossRef

Tully P, Baker R (2012) Depression, anxiety, and cardiac morbidity outcomes after coronary artery bypass surgery: a contemporary and practical review. J Geriatr Cardiol 9:197–208CrossRef

van der Linden P, Gazdzik T et al (2011) A double blind, randomized, multiucenter study of MP4OX for treatment of perioperative hypotension in patients undergoing primary hip arthroplasty under spinal anesthesia. Anesth Analg 112:759–773CrossRef

Vlahakes G (2000) Hemoglobin solutions come of age. Anesthesiology 92:637–638CrossRef

Wagner P (2011) Modeling O2 transport as an integrated system limiting VO2MAX. Comput Methods Programs Biomed 101:109–114CrossRef

Weiskopf R (2010) Hemoglobin-based oxygen carriers: compassionate use and compassionate clinical trials (invited comment). Anesth Analg 110:659–662CrossRef

Yu B, Raher M et al (2008) Inhaled nitric oxide enables artificial blood transfusion without hypertension. Circulation 117:1982–1990CrossRef

Yu B, Bloch K et al (2009a) Hemoglobin based red blood cell substitutes and nitric oxide. Trends Cardiovasc Med 19:103–107CrossRef

Yu B, Volpato G et al (2009b) Prevention of the pulmonary vasoconstrictor effects of HBOC-201 in awake lambs by continuously breathing nitric oxide. Anesthesiology 110:113–122CrossRef

Titel: Some Critical Comments on the Major HBOC Clinical Trials
verfasst von: George P. Biro
Verlag: Springer Berlin Heidelberg
Buch: Hemoglobin-Based Oxygen Carriers as Red Cell Substitutes and Oxygen Therapeutics
Print ISBN: 978-3-642-40716-1

Electronic ISBN: 978-3-642-40717-8

Copyright-Jahr: 2013
DOI: https://doi.org/10.1007/978-3-642-40717-8_30

Premium Partner

Marktübersichten

Die im Laufe eines Jahres in der „adhäsion“ veröffentlichten Marktübersichten helfen Anwendern verschiedenster Branchen, sich einen gezielten Überblick über Lieferantenangebote zu verschaffen.

Zur Marktübersicht