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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.
 
ClinicalTrials.gov Identifier: NCT01004198
Recruitment Status : Completed
First Posted : October 29, 2009
Last Update Posted : August 19, 2013
Sponsor:
Information provided by (Responsible Party):
Sangart

Tracking Information
First Submitted Date  ICMJE October 28, 2009
First Posted Date  ICMJE October 29, 2009
Last Update Posted Date August 19, 2013
Study Start Date  ICMJE December 2009
Actual Primary Completion Date June 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 28, 2009)
Serum lactate clearance [ Time Frame: 2 hours ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2009)
  • All-cause mortality [ Time Frame: 28 days ]
  • Ventilator-free days [ Time Frame: 28 days ]
  • ICU-free days [ Time Frame: 28 days ]
  • Hospital-free days [ Time Frame: 28 days ]
  • Sepsis-related Organ Failure Assessment (SOFA) score [ Time Frame: Daily ]
  • Modified Denver score [ Time Frame: Daily ]
  • Composite endpoint of Time to Complete Organ Failure Resolution (CTCOFR) [ Time Frame: At 14 and 21 days ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase IIa Study of MP4OX in Traumatic Hemorrhagic Shock Patients
Official Title  ICMJE 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
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Shock, Hemorrhagic
  • Shock, Traumatic
  • Acidosis, Lactic
Intervention  ICMJE
  • Drug: MP4OX
    4.3 g/dL PEG-Hb solution in lactated electrolyte solution
    Other Names:
    • MP4
    • MalPEG-Hb
    • PEG-Hb
    • Pegylated-Hb
  • Drug: Ringers Lactate solution
    Ringers Lactate solution for Injection
    Other Names:
    • Lactated Ringers
    • Hartmann's solution
Study Arms  ICMJE
  • Experimental: MP4OX - 250
    250 mL dose
    Intervention: Drug: MP4OX
  • Experimental: MP4OX - 500
    500 mL dose
    Intervention: Drug: MP4OX
  • Active Comparator: Ringers Lactate solution
    500 mL dose
    Intervention: Drug: Ringers Lactate solution
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 21, 2010)
51
Original Estimated Enrollment  ICMJE
 (submitted: October 28, 2009)
75
Actual Study Completion Date  ICMJE June 2010
Actual Primary Completion Date June 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Germany,   South Africa,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01004198
Other Study ID Numbers  ICMJE TRA-204
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sangart
Study Sponsor  ICMJE Sangart
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Karim Brohi, MD The Royal London Hospital
PRS Account Sangart
Verification Date August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP