Phase IIa Study of MP4OX in Traumatic Hemorrhagic Shock Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sangart
ClinicalTrials.gov Identifier:
NCT01004198
First received: October 28, 2009
Last updated: August 15, 2013
Last verified: August 2013
  Purpose

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 Intervention Phase
Shock, Hemorrhagic
Shock, Traumatic
Acidosis, Lactic
Drug: MP4OX
Drug: Ringers Lactate solution
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Sangart:

Primary Outcome Measures:
  • Serum lactate clearance [ Time Frame: 2 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • All-cause mortality [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Ventilator-free days [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • ICU-free days [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Hospital-free days [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Sepsis-related Organ Failure Assessment (SOFA) score [ Time Frame: Daily ] [ Designated as safety issue: Yes ]
  • Modified Denver score [ Time Frame: Daily ] [ Designated as safety issue: Yes ]
  • Composite endpoint of Time to Complete Organ Failure Resolution (CTCOFR) [ Time Frame: At 14 and 21 days ] [ Designated as safety issue: Yes ]

Enrollment: 51
Study Start Date: December 2009
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
  • Ringers Lactate solution
  • Hartmann's solution

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01004198

Locations
France
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
Germany
Charité Campus Virchow Klinikum
Berlin, Germany
Klinikum der Johann-Wolfgang-Goethe-Universität
Frankfurt, Germany
South Africa
Netcare Union Hospital
Alberton, South Africa
Netcare Milpark Hospital
Johannesburg, South Africa
Charlotte Maxeke Johannesburg Hospital
Johannesburg, South Africa
Steve Biko Academic Hospital
Pretoria, South Africa
Netcare Unitas Hospital, Centurian
Pretoria, South Africa
Chris Hani Baragwanath Hospital
Soweto, South Africa
United Kingdom
The Royal London Hospital
London, United Kingdom
Sponsors and Collaborators
Sangart
Investigators
Principal Investigator: Karim Brohi, MD The Royal London Hospital
  More Information

Additional Information:
Publications:

Responsible Party: Sangart
ClinicalTrials.gov Identifier: NCT01004198     History of Changes
Other Study ID Numbers: TRA-204
Study First Received: October 28, 2009
Last Updated: August 15, 2013
Health Authority: South Africa: Medicines Control Council
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut

Keywords provided by Sangart:
Trauma
Hemorrhage
Hemorrhagic shock
Lactic acidosis
Oxygen carriers
Oxygen therapeutics
Hemoglobin solutions
Hemoglobin substitutes
Red cell substitutes
PEG-hemoglobin

Additional relevant MeSH terms:
Acidosis
Acidosis, Lactic
Shock
Shock, Hemorrhagic
Shock, Traumatic
Acid-Base Imbalance
Metabolic Diseases
Pathologic Processes
Hemorrhage
Wounds and Injuries
Blood Substitutes
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014