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”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: July 2010

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(s) in this Clinical Trial

• Drug: MP4OX
  • 4.3 g/dL PEG-Hb solution in lactated electrolyte solution
• Drug: MP4OX
  • 4.3 g/dL PEG-Hb solution in lactated electrolyte solution
• Drug: Ringer's Lactate solution
  • 500 mL infusion

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: MP4OX - 250
  • 250 mL dose
• Experimental: MP4OX - 500
  • 500 mL dose
• Placebo Comparator: R-L Control
  • 500 mL of Ringer's Lactate solution

Primary Measures

• Serum lactate clearance
  • Time Frame: 2 hours
    Safety Issue?: No

Secondary Measures

• All-cause mortality
  • Time Frame: 28 days
    Safety Issue?: Yes
• Ventilator-free days
  • Time Frame: 28 days
    Safety Issue?: No
• ICU-free days
  • Time Frame: 28 days
    Safety Issue?: No
• Hospital-free days
  • Time Frame: 28 days
    Safety Issue?: No
• Sepsis-related Organ Failure Assessment (SOFA) score
  • Time Frame: Daily
    Safety Issue?: Yes
• Modified Denver score
  • Time Frame: Daily
    Safety Issue?: Yes
• Composite endpoint of Time to Complete Organ Failure Resolution (CTCOFR)
  • Time Frame: At 14 and 21 days
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Sangart

Overall Clinical Trial Officials and Contacts

Howard Levy, MD, PhD Study Director Sangart, Inc. (San Diego, CA)  

Overall Contact: Karim Brohi, MD +44 (0) 207 377 7695 Karim.brohi@bartsandthelondon.nhs.uk

Information obtained from ClinicalTrials.gov on February 04, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01004198

Study ID Number: MP4OX-09-TRA-204

ClinicalTrials.gov Identifier: NCT01004198

Health Authority: South Africa: Medicines Control Council

www.Sangart.com