NCT01004198

Brief Summary

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
51

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Dec 2009

Shorter than P25 for phase_2

Geographic Reach
4 countries

13 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 28, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 29, 2009

Completed
1 month until next milestone

Study Start

First participant enrolled

December 1, 2009

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2010

Completed
Last Updated

August 19, 2013

Status Verified

August 1, 2013

Enrollment Period

6 months

First QC Date

October 28, 2009

Last Update Submit

August 15, 2013

Conditions

Shock, HemorrhagicShock, TraumaticAcidosis, Lactic

Keywords

TraumaHemorrhageHemorrhagic shockLactic acidosisOxygen carriersOxygen therapeuticsHemoglobin solutionsHemoglobin substitutesRed cell substitutesPEG-hemoglobin

Outcome Measures

Primary Outcomes (1)

  • Serum lactate clearance

    2 hours

Secondary Outcomes (7)

  • All-cause mortality

    28 days

  • Ventilator-free days

    28 days

  • ICU-free days

    28 days

  • Hospital-free days

    28 days

  • Sepsis-related Organ Failure Assessment (SOFA) score

    Daily

  • +2 more secondary outcomes

Study Arms (3)

MP4OX - 250

EXPERIMENTAL

250 mL dose

Drug: MP4OX

MP4OX - 500

EXPERIMENTAL

500 mL dose

Drug: MP4OX

Ringers Lactate solution

ACTIVE COMPARATOR

500 mL dose

Drug: Ringers Lactate solution

Interventions

MP4OXDRUG

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

Also known as: MP4, MalPEG-Hb, PEG-Hb, Pegylated-Hb
MP4OX - 250
Ringers Lactate solutionDRUG

Ringers Lactate solution for Injection

Also known as: Lactated Ringers, Hartmann's solution
Ringers Lactate solution

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (13)

Centre Hospitalier de Bicêtre

Le Kremlin-Bicêtre, France

Location

CHRU de Lille - Hôpital Claude Huriez

Lille, France

Location

Hôpital Dupuytren

Limoges, France

Location

Hôpital Pitié-Salpêtrière

Paris, France

Location

Charité Campus Virchow Klinikum

Berlin, Germany

Location

Klinikum der Johann-Wolfgang-Goethe-Universität

Frankfurt, Germany

Location

Netcare Union Hospital

Alberton, South Africa

Location

Charlotte Maxeke Johannesburg Hospital

Johannesburg, South Africa

Location

Netcare Milpark Hospital

Johannesburg, South Africa

Location

Netcare Unitas Hospital, Centurian

Pretoria, South Africa

Location

Steve Biko Academic Hospital

Pretoria, South Africa

Location

Chris Hani Baragwanath Hospital

Soweto, South Africa

Location

The Royal London Hospital

London, United Kingdom

Location

Related Publications (10)

  • 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.

    PMID: 17122578BACKGROUND

  • 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.

    PMID: 18279190BACKGROUND

  • 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.

    PMID: 18948027BACKGROUND

  • 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.

    PMID: 18212644BACKGROUND

  • 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.

    PMID: 16096458BACKGROUND

  • 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.

    PMID: 14729723BACKGROUND

  • 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.

    PMID: 19178457BACKGROUND

  • 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.

    PMID: 18837531BACKGROUND

  • 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.

    PMID: 16857991BACKGROUND

  • 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.

    PMID: 21317165BACKGROUND

Related Links

MeSH Terms

Conditions

Shock, HemorrhagicShock, TraumaticAcidosis, LacticWounds and InjuriesHemorrhage

Interventions

maleimide-polyethylene glycol-modified hemoglobin, MP4PEG-hemoglobinRinger's Lactate

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and SymptomsShockAcidosisAcid-Base ImbalanceMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Crystalloid SolutionsIsotonic SolutionsSolutionsPharmaceutical Preparations

Study Officials

  • Karim Brohi, MD

    The Royal London Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 28, 2009

First Posted

October 29, 2009

Study Start

December 1, 2009

Primary Completion

June 1, 2010

Study Completion

June 1, 2010

Last Updated

August 19, 2013

Record last verified: 2013-08

Locations

GB(1)FR(4)ZA(6)DE(2)