Working… Menu

Phase IIa Study of MP4OX in Traumatic Hemorrhagic Shock Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01004198
Recruitment Status : Completed
First Posted : October 29, 2009
Last Update Posted : August 19, 2013
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Shock, Hemorrhagic Shock, Traumatic Acidosis, Lactic Drug: MP4OX Drug: Ringers Lactate solution Phase 2

Detailed Description:

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 51 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Double-blind, Controlled Dose-finding Study to Evaluate the Safety and Efficacy of MP4OX Treatment Plus Standard of Care in Severely Injured Trauma Patients With Lactic Acidosis Due to Hemorrhagic Shock
Study Start Date : December 2009
Actual Primary Completion Date : June 2010
Actual Study Completion Date : June 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Shock

Arm Intervention/treatment
Experimental: MP4OX - 250
250 mL dose
Drug: MP4OX
4.3 g/dL PEG-Hb solution in lactated electrolyte solution
Other Names:
  • MP4
  • MalPEG-Hb
  • PEG-Hb
  • Pegylated-Hb

Experimental: MP4OX - 500
500 mL dose
Drug: MP4OX
4.3 g/dL PEG-Hb solution in lactated electrolyte solution
Other Names:
  • MP4
  • MalPEG-Hb
  • PEG-Hb
  • Pegylated-Hb

Active Comparator: Ringers Lactate solution
500 mL dose
Drug: Ringers Lactate solution
Ringers Lactate solution for Injection
Other Names:
  • Lactated Ringers
  • Hartmann's solution

Primary Outcome Measures :
  1. Serum lactate clearance [ Time Frame: 2 hours ]

Secondary Outcome Measures :
  1. All-cause mortality [ Time Frame: 28 days ]
  2. Ventilator-free days [ Time Frame: 28 days ]
  3. ICU-free days [ Time Frame: 28 days ]
  4. Hospital-free days [ Time Frame: 28 days ]
  5. Sepsis-related Organ Failure Assessment (SOFA) score [ Time Frame: Daily ]
  6. Modified Denver score [ Time Frame: Daily ]
  7. Composite endpoint of Time to Complete Organ Failure Resolution (CTCOFR) [ Time Frame: At 14 and 21 days ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01004198

Layout table for location information
Centre Hospitalier de Bicêtre
Le Kremlin Bicetre, France
CHRU de Lille - Hôpital Claude Huriez
Lille, France
Hôpital Dupuytren
Limoges, France
Hôpital Pitié-Salpêtrière
Paris, France
Charité Campus Virchow Klinikum
Berlin, Germany
Klinikum der Johann-Wolfgang-Goethe-Universität
Frankfurt, Germany
South Africa
Netcare Union Hospital
Alberton, South Africa
Charlotte Maxeke Johannesburg Hospital
Johannesburg, South Africa
Netcare Milpark Hospital
Johannesburg, South Africa
Netcare Unitas Hospital, Centurian
Pretoria, South Africa
Steve Biko Academic Hospital
Pretoria, South Africa
Chris Hani Baragwanath Hospital
Soweto, South Africa
United Kingdom
The Royal London Hospital
London, United Kingdom
Sponsors and Collaborators
Layout table for investigator information
Principal Investigator: Karim Brohi, MD The Royal London Hospital
Additional Information:

Layout table for additonal information
Responsible Party: Sangart Identifier: NCT01004198    
Other Study ID Numbers: TRA-204
First Posted: October 29, 2009    Key Record Dates
Last Update Posted: August 19, 2013
Last Verified: August 2013
Keywords provided by Sangart:
Hemorrhagic shock
Lactic acidosis
Oxygen carriers
Oxygen therapeutics
Hemoglobin solutions
Hemoglobin substitutes
Red cell substitutes
Additional relevant MeSH terms:
Layout table for MeSH terms
Acidosis, Lactic
Shock, Hemorrhagic
Shock, Traumatic
Pathologic Processes
Acid-Base Imbalance
Metabolic Diseases
Wounds and Injuries
Pharmaceutical Solutions