Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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WITHDRAWN
PHASE2
INTERVENTIONAL
2013-12-31
2016-03-31
Brief Summary
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Detailed Description
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Despite optimal care, organ dysfunction is present in many patients as evidenced by persistent lactic acidosis. Blood transfusions are intended to improve circulation of oxygen-carrying red blood cells, but are frequently insufficient, even when the hemoglobin level is optimized. The severity of lactic acidosis in trauma victims has also been shown to correlate with worse outcome.
Support for the proposed application for MP4OX as a therapeutic adjunct to standard treatment of severe hemorrhage shock, is based on multiple preclinical studies in different animal models of hemorrhagic shock resuscitation. These preclinical studies demonstrated that survival was greater and restoration of acid-base status and hemodynamics were improved with MP4OX. The benefits of MP4OX in animals were observed with or without co-administration of autologous blood, demonstrating that red cell transfusion alone was insufficient, and that the effects of MP4OX were additive.
The hypothesis for the current study is that MP4OX will enhance perfusion and oxygenation of ischemic organs and thereby prevent and reduce the duration of organ failure and improve morbidity and mortality outcome measures.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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MP4OX 500-mL
500-mL dose of MP4OX
MP4OX
4.3 g/dL pegylated hemoglobin in balanced lactate-electrolyte solution
MP4OX 750-mL
750-mL dose of MP4OX
MP4OX
4.3 g/dL pegylated hemoglobin in balanced lactate-electrolyte solution
Control
Standard crystalloid Keep Vein Open (KVO) infusion
Control
Crystalloid solution IV infusion drip to keep vein open
Interventions
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MP4OX
4.3 g/dL pegylated hemoglobin in balanced lactate-electrolyte solution
Control
Crystalloid solution IV infusion drip to keep vein open
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Acidosis (blood lactate level ≥ 5 mmol/L; equivalent to 45 mg/dL)
Exclusion Criteria
* Normalization of lactate prior to dosing (≤ 2.2 mmol/L)
* Evidence of severe traumatic brain injury (TBI) as defined by ANY one of the following: Known non-survivable head injury or open brain injury; Known AIS (head region) ≥ 4 by an appropriate imaging methodology; Contemplated CNS surgery; Abnormal physical exam indicative of severe CNS or any spinal cord injury above T5 level; or Glasgow Coma Score (GCS) = 3, 4 or 5.
* Cardiac arrest prior to randomization
* Known age below the legal age for consenting
* Estimated time from injury to randomization \> 4 hours
* Estimated time from hospital admission to randomization \> 2 hours
* Known pregnancy
* Use of any oxygen carrier other than RBCs
* Known previous participation in this study
* Professional or ancillary personnel involved with this study
* Known receipt of any investigational drug(s) within 30 days prior to study
18 Years
ALL
No
Sponsors
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Sangart
INDUSTRY
Responsible Party
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Principal Investigators
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Karim Brohi, MD
Role: PRINCIPAL_INVESTIGATOR
The Royal London Hospital
Frank V. Booth, BCh, FACS
Role: STUDY_CHAIR
Sangart, Inc.
Locations
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Liverpool Hospital
Liverpool, , Australia
John Hunter Hospital
Newcastle, , Australia
Erasme University Hospital
Brussels, , Belgium
University Hospital Antwerpen
Edegem, , Belgium
Faculdade de Medicina de S. J. Do Rio Preto
São José do Rio Preto, , Brazil
Hopital Universitário, Centro de Estudos em Emergências em Saúde, USP Ribeirão Preto
São Paulo, , Brazil
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo - FMUSP
São Paulo, , Brazil
Hôpital Beaujon
Clichy, , France
Hôpital du Kremlin Bicêtre
Le Kremlin-Bicêtre, , France
Hôpital Roger Salengro, CHRU Lille
Lille, , France
CHU Dupuytren
Limoges, , France
Hôpital Edouard Herriot
Lyon, , France
Hôpital Pitié-Salpêtrière
Paris, , France
Universitätsklinikum der Rheinisch-Westfälische Technische Hochschule Aachen
Aachen, , Germany
Campus Virchow Klinikum Charité Berlin
Berlin, , Germany
Kliniken der Stadt Köln gGmbH Krankenhaus Merheim
Cologne, , Germany
Klinikum der J.-W.-Goethe-Universität Frankfurt a.M.
Franfurt, , Germany
BG Klinik Ludwigshafen
Ludwigshafen, , Germany
Soroka University Medical Center
Beersheba, , Israel
Rambam Health Care Campus
Haifa, , Israel
Hadassah Medical Organization, Hadassah University Hospital, Ein-Karem
Jerusalem, , Israel
Auckland City Hospital
Auckland, , New Zealand
Oslo University Hospital Ullevaal
Oslo, , Norway
Netcare Union Hospital
Alberton, , South Africa
Vincent Palotti Dr Christiaan Barnard Memorial Hospital
Cape Town, , South Africa
Charlotte Maxeke Johannesburg Academic Hospita
Johannesburg, , South Africa
Netcare Milpark Hospital
Johannesburg, , South Africa
Chris Hani Baragwanath Hospital
Soweto, , South Africa
CHU Vaudois
Lausanne, , Switzerland
UniversitätsSpital Zürich
Zurich, , Switzerland
The Royal London Hospital
London, , United Kingdom
Countries
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References
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Cole RH, Vandegriff KD. MP4, a vasodilatory PEGylated hemoglobin. Adv Exp Med Biol. 2011;701:85-90. doi: 10.1007/978-1-4419-7756-4_12.
Young MA, Lohman J, Malavalli A, Vandegriff KD, Winslow RM. Hemospan improves outcome in a model of perioperative hemodilution and blood loss in the rat: comparison with hydroxyethyl starch. J Cardiothorac Vasc Anesth. 2009 Jun;23(3):339-47. doi: 10.1053/j.jvca.2008.08.006. Epub 2008 Oct 22.
Vandegriff KD, Winslow RM. Hemospan: design principles for a new class of oxygen therapeutic. Artif Organs. 2009 Feb;33(2):133-8. doi: 10.1111/j.1525-1594.2008.00697.x.
Vandegriff KD, Malavalli A, Mkrtchyan GM, Spann SN, Baker DA, Winslow RM. Sites of modification of hemospan, a poly(ethylene glycol)-modified human hemoglobin for use as an oxygen therapeutic. Bioconjug Chem. 2008 Nov 19;19(11):2163-70. doi: 10.1021/bc8002666.
Svergun DI, Ekstrom F, Vandegriff KD, Malavalli A, Baker DA, Nilsson C, Winslow RM. Solution structure of poly(ethylene) glycol-conjugated hemoglobin revealed by small-angle X-ray scattering: implications for a new oxygen therapeutic. Biophys J. 2008 Jan 1;94(1):173-81. doi: 10.1529/biophysj.107.114314. Epub 2007 Sep 7.
Cole RH, Vandegriff KD, Szeri AJ, Savas O, Baker DA, Winslow RM. A quantitative framework for the design of acellular hemoglobins as blood substitutes: implications of dynamic flow conditions. Biophys Chem. 2007 Jun;128(1):63-74. doi: 10.1016/j.bpc.2007.03.004. Epub 2007 Mar 13.
Young MA, Riddez L, Kjellstrom BT, Bursell J, Winslow F, Lohman J, Winslow RM. MalPEG-hemoglobin (MP4) improves hemodynamics, acid-base status, and survival after uncontrolled hemorrhage in anesthetized swine. Crit Care Med. 2005 Aug;33(8):1794-804. doi: 10.1097/01.ccm.0000172648.55309.13.
Drobin D, Kjellstrom BT, Malm E, Malavalli A, Lohman J, Vandegriff KD, Young MA, Winslow RM. Hemodynamic response and oxygen transport in pigs resuscitated with maleimide-polyethylene glycol-modified hemoglobin (MP4). J Appl Physiol (1985). 2004 May;96(5):1843-53. doi: 10.1152/japplphysiol.00530.2003. Epub 2004 Jan 16.
Winslow RM, Lohman J, Malavalli A, Vandegriff KD. Comparison of PEG-modified albumin and hemoglobin in extreme hemodilution in the rat. J Appl Physiol (1985). 2004 Oct;97(4):1527-34. doi: 10.1152/japplphysiol.00404.2004. Epub 2004 Jun 18.
Vandegriff KD, Bellelli A, Samaja M, Malavalli A, Brunori M, Winslow RM. Kinetics of NO and O2 binding to a maleimide poly(ethylene glycol)-conjugated human haemoglobin. Biochem J. 2004 Aug 15;382(Pt 1):183-9. doi: 10.1042/BJ20040156.
Tsai AG, Vandegriff KD, Intaglietta M, Winslow RM. Targeted O2 delivery by low-P50 hemoglobin: a new basis for O2 therapeutics. Am J Physiol Heart Circ Physiol. 2003 Oct;285(4):H1411-9. doi: 10.1152/ajpheart.00307.2003. Epub 2003 Jun 12.
Vandegriff KD, Malavalli A, Wooldridge J, Lohman J, Winslow RM. MP4, a new nonvasoactive PEG-Hb conjugate. Transfusion. 2003 Apr;43(4):509-16. doi: 10.1046/j.1537-2995.2003.00341.x.
McCarthy MR, Vandegriff KD, Winslow RM. The role of facilitated diffusion in oxygen transport by cell-free hemoglobins: implications for the design of hemoglobin-based oxygen carriers. Biophys Chem. 2001 Aug 30;92(1-2):103-17. doi: 10.1016/s0301-4622(01)00194-6.
Young MA, Riddez L, Kjellstrom BT, Winslow RM. Effect of maleimide-polyethylene glycol hemoglobin (MP4) on hemodynamics and acid-base status after uncontrolled hemorrhage in anesthetized swine: comparison with crystalloid and blood. J Trauma. 2007 Dec;63(6):1234-44. doi: 10.1097/TA.0b013e31815bd7b0.
Wettstein R, Tsai AG, Erni D, Winslow RM, Intaglietta M. Resuscitation with polyethylene glycol-modified human hemoglobin improves microcirculatory blood flow and tissue oxygenation after hemorrhagic shock in awake hamsters. Crit Care Med. 2003 Jun;31(6):1824-30. doi: 10.1097/01.CCM.0000069340.16319.F2.
Husain FA, Martin MJ, Mullenix PS, Steele SR, Elliott DC. Serum lactate and base deficit as predictors of mortality and morbidity. Am J Surg. 2003 May;185(5):485-91. doi: 10.1016/s0002-9610(03)00044-8.
Regnier MA, Raux M, Le Manach Y, Asencio Y, Gaillard J, Devilliers C, Langeron O, Riou B. Prognostic significance of blood lactate and lactate clearance in trauma patients. Anesthesiology. 2012 Dec;117(6):1276-88. doi: 10.1097/ALN.0b013e318273349d.
McNelis J, Marini CP, Jurkiewicz A, Szomstein S, Simms HH, Ritter G, Nathan IM. Prolonged lactate clearance is associated with increased mortality in the surgical intensive care unit. Am J Surg. 2001 Nov;182(5):481-5. doi: 10.1016/s0002-9610(01)00755-3.
Abramson D, Scalea TM, Hitchcock R, Trooskin SZ, Henry SM, Greenspan J. Lactate clearance and survival following injury. J Trauma. 1993 Oct;35(4):584-8; discussion 588-9. doi: 10.1097/00005373-199310000-00014.
Tsai AG, Cabrales P, Manjula BN, Acharya SA, Winslow RM, Intaglietta M. Dissociation of local nitric oxide concentration and vasoconstriction in the presence of cell-free hemoglobin oxygen carriers. Blood. 2006 Nov 15;108(10):3603-10. doi: 10.1182/blood-2006-02-005272. Epub 2006 Jul 20.
Related Links
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Sangart Inc. (San Diego, CA) web site \[Study SPONSOR\]
Other Identifiers
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TRA-207
Identifier Type: -
Identifier Source: org_study_id