Phase IIa Study of MP4OX in Traumatic Hemorrhagic Shock Patients
Condition: Shock, Hemorrhagic; Shock, Traumatic; Acidosis, Lactic
MeSH terms: Acidosis; Acidosis, Lactic; Shock; Shock, Hemorrhagic; Shock, Traumatic
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): MP4OX; MP4OX; Ringers Lactate solution
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 4.3 g/dL PEG-Hb solution in lactated electrolyte solution; 4.3 g/dL PEG-Hb solution in lactated electrolyte solution; Ringers Lactate solution for Injection
Other intervention name(s): MP4; MalPEG-Hb; PEG-Hb; Pegylated-Hb; MP4; MalPEG-Hb; PEG-Hb; Pegylated-Hb; Lactated Ringers; Hartmann's solution
Intervention MeSH terms: Pharmaceutical Solutions
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Trauma; Hemorrhage; Hemorrhagic shock; Lactic acidosis; Oxygen carriers; Oxygen therapeutics; Hemoglobin solutions; Hemoglobin substitutes; Red cell substitutes; PEG-hemoglobin