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Phase IIa Study of MP4OX in Traumatic Hemorrhagic Shock Patients

NCT ID: NCT01004198

Last Updated: 2013-08-19

Study Results

Results pending

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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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

51 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-12-31

Study Completion Date

2010-06-30

Brief Summary

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MP4OX is a novel oxygen therapeutic agent specifically developed to perfuse and oxygenate tissue at risk for ischemia and hypoxia. MP4OX is a pegylated hemoglobin-based colloid and and as a result of its molecular size and unique oxygen dissociation characteristics, targets oxygen delivery to ischemic tissues by selectively off-loading oxygen in tissues predisposed to low oxygen tension. Sangart is currently evaluating MP4OX to reduce organ dysfunction and failure in trauma patients with lactic acidosis due to severe hemorrhagic shock.

Detailed Description

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Acute traumatic injury, including both blunt and penetrating injury, is often associated with severe bleeding which can lead to hemorrhagic shock. During shock, inadequate perfusion of critical organs can lead to local ischemia and tissue hypoxia (insufficient oxygenation), which can be detected by an increase in serum lactate levels. Despite optimal care, more than 10% of trauma victims who reach hospital alive will die, and many will suffer from organ failure. Death and significant, persistent morbidity are consequences of trauma, and traumatic injuries are associated with lost productivity, reduced quality of life, and direct costs to patients and health care systems worldwide. Current therapies, which also include blood transfusion, are aimed at supporting failing organs, but a therapeutic agent that could help to quickly restore adequate oxygenation may be beneficial to prevent or shorten duration of organ failure and improve patient outcome.

Direct support for the proposed clinical application to use MP4OX in resuscitation from hemorrhage is found in preclinical animal studies. Using a pig model of uncontrolled hemorrhage and resuscitation, survival was greater and restoration of hemodynamics and acid-base status were improved with MP4OX relative to an equivalent volume of crystalloid, pentastarch, or unmodified hemoglobin. Administration of MP4OX improved 24-hour survival, stabilized cardiac output and arterial pressure at nearly normal levels, and reduced lactate levels more effectively than the control fluids. Importantly, these benefits of MP4OX were observed with or without co-administration of autologous blood, suggesting that blood alone was not sufficient to achieve complete resuscitation, and that the effects of MP4OX appear to be additional to those of blood.

Conditions

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Shock, Hemorrhagic Shock, Traumatic Acidosis, Lactic

Keywords

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Trauma Hemorrhage Hemorrhagic shock Lactic acidosis Oxygen carriers Oxygen therapeutics Hemoglobin solutions Hemoglobin substitutes Red cell substitutes PEG-hemoglobin

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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MP4OX - 250

250 mL dose

Group Type EXPERIMENTAL

MP4OX

Intervention Type DRUG

4.3 g/dL PEG-Hb solution in lactated electrolyte solution

MP4OX - 500

500 mL dose

Group Type EXPERIMENTAL

MP4OX

Intervention Type DRUG

4.3 g/dL PEG-Hb solution in lactated electrolyte solution

Ringers Lactate solution

500 mL dose

Group Type ACTIVE_COMPARATOR

Ringers Lactate solution

Intervention Type DRUG

Ringers Lactate solution for Injection

Interventions

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MP4OX

4.3 g/dL PEG-Hb solution in lactated electrolyte solution

Intervention Type DRUG

MP4OX

4.3 g/dL PEG-Hb solution in lactated electrolyte solution

Intervention Type DRUG

Ringers Lactate solution

Ringers Lactate solution for Injection

Intervention Type DRUG

Other Intervention Names

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MP4 MalPEG-Hb PEG-Hb Pegylated-Hb MP4 MalPEG-Hb PEG-Hb Pegylated-Hb Lactated Ringers Hartmann's solution

Eligibility Criteria

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Inclusion Criteria

* Adult male or female (surgically sterile or post-menopausal or confirmed not to be pregnant)
* Trauma injury (blunt and/or penetrating) resulting in lactic acidosis due to hemorrhagic shock (blood lactate level ≥ 5 mmol/L; equivalent to ≥ 45 mg/dL)
* Informed consent obtained before any study-related activities

Exclusion Criteria

* Not expected to survive 24 hours after randomization
* Evidence of severe traumatic brain injury as defined by any one of the following: Known non-survivable head injury or open brain injury; Glasgow Coma Score (GCS) = 3, 4 or 5, or known AIS = 5 if GCS \> 5; Immediate open intracranial operation; Abnormal physical exam indicative of severe CNS or spinal injury
* Significant ongoing uncontrolled hemorrhage where control of bleeding is not expected within 2 hours of randomization
* Cardiac arrest prior to dosing
* Estimated time from injury to dosing \> 4 hours
* Estimated time from hospital admission to randomization \> 2 hours
* Known or suspected pregnancy (confirmed by urine test)
* Previous participation in this study
* Professional or ancillary personnel involved with this study
* Receipt of any investigational drug(s) within 30 days prior to study
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sangart

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Karim Brohi, MD

Role: PRINCIPAL_INVESTIGATOR

The Royal London Hospital

Locations

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Centre Hospitalier de Bicêtre

Le Kremlin-Bicêtre, , France

Site Status

CHRU de Lille - Hôpital Claude Huriez

Lille, , France

Site Status

Hôpital Dupuytren

Limoges, , France

Site Status

Hôpital Pitié-Salpêtrière

Paris, , France

Site Status

Charité Campus Virchow Klinikum

Berlin, , Germany

Site Status

Klinikum der Johann-Wolfgang-Goethe-Universität

Frankfurt, , Germany

Site Status

Netcare Union Hospital

Alberton, , South Africa

Site Status

Charlotte Maxeke Johannesburg Hospital

Johannesburg, , South Africa

Site Status

Netcare Milpark Hospital

Johannesburg, , South Africa

Site Status

Netcare Unitas Hospital, Centurian

Pretoria, , South Africa

Site Status

Steve Biko Academic Hospital

Pretoria, , South Africa

Site Status

Chris Hani Baragwanath Hospital

Soweto, , South Africa

Site Status

The Royal London Hospital

London, , United Kingdom

Site Status

Countries

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France Germany South Africa United Kingdom

References

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Olofsson C, Ahl T, Johansson T, Larsson S, Nellgard P, Ponzer S, Fagrell B, Przybelski R, Keipert P, Winslow N, Winslow RM. A multicenter clinical study of the safety and activity of maleimide-polyethylene glycol-modified Hemoglobin (Hemospan) in patients undergoing major orthopedic surgery. Anesthesiology. 2006 Dec;105(6):1153-63. doi: 10.1097/00000542-200612000-00015.

Reference Type BACKGROUND
PMID: 17122578 (View on PubMed)

Olofsson C, Nygards EB, Ponzer S, Fagrell B, Przybelski R, Keipert PE, Winslow N, Winslow RM. A randomized, single-blind, increasing dose safety trial of an oxygen-carrying plasma expander (Hemospan) administered to orthopaedic surgery patients with spinal anaesthesia. Transfus Med. 2008 Feb;18(1):28-39. doi: 10.1111/j.1365-3148.2007.00811.x.

Reference Type BACKGROUND
PMID: 18279190 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18948027 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18212644 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16096458 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14729723 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19178457 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18837531 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16857991 (View on PubMed)

van der Linden P, Gazdzik TS, Jahoda D, Heylen RJ, Skowronski JC, Pellar D, Kofranek I, Gorecki AZ, Fagrell B, Keipert PE, Hardiman YJ, Levy H; 6090 Study Investigators. A double-blind, randomized, multicenter study of MP4OX for treatment of perioperative hypotension in patients undergoing primary hip arthroplasty under spinal anesthesia. Anesth Analg. 2011 Apr;112(4):759-73. doi: 10.1213/ANE.0b013e31820c7b5f. Epub 2011 Feb 11.

Reference Type BACKGROUND
PMID: 21317165 (View on PubMed)

Related Links

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http://www.sangart.com

www.Sangart.com

Other Identifiers

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TRA-204

Identifier Type: -

Identifier Source: org_study_id