Phase IIa Study of MP4OX in Traumatic Hemorrhagic Shock Patients

August 15, 2013 updated by: Sangart

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 Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

51

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Le Kremlin Bicetre, France
        • Centre Hospitalier de Bicêtre
      • Lille, France
        • CHRU de Lille - Hopital Claude Huriez
      • Limoges, France
        • Hopital DUPUYTREN
      • Paris, France
        • Hôpital Pitié-Salpétrière
  • Germany
      • Berlin, Germany
        • Charite Campus Virchow Klinikum
      • Frankfurt, Germany
        • Klinikum der Johann-Wolfgang-Goethe-Universität
  • South Africa
      • Alberton, South Africa
        • Netcare Union Hospital
      • Johannesburg, South Africa
        • Netcare Milpark Hospital
      • Johannesburg, South Africa
        • Charlotte Maxeke Johannesburg Hospital
      • Pretoria, South Africa
        • Steve Biko Academic Hospital
      • Pretoria, South Africa
        • Netcare Unitas Hospital, Centurian
      • Soweto, South Africa
        • Chris Hani Baragwanath Hospital
  • United Kingdom
      • London, United Kingdom
        • The Royal London Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: MP4OX - 250
250 mL dose
Drug: MP4OX
4.3 g/dL PEG-Hb solution in lactated electrolyte solution
Other Names:
  • MalPEG-Hb
  • MP4
  • 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:
  • MalPEG-Hb
  • MP4
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Serum lactate clearance
Time Frame: 2 hours
2 hours

Secondary Outcome Measures

Outcome Measure
Time Frame
Ventilator-free days
Time Frame: 28 days
28 days
ICU-free days
Time Frame: 28 days
28 days
All-cause mortality
Time Frame: 28 days
28 days
Hospital-free days
Time Frame: 28 days
28 days
Sepsis-related Organ Failure Assessment (SOFA) score
Time Frame: Daily
Daily
Modified Denver score
Time Frame: Daily
Daily
Composite endpoint of Time to Complete Organ Failure Resolution (CTCOFR)
Time Frame: At 14 and 21 days
At 14 and 21 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sangart

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2009

Primary Completion (ACTUAL)

June 1, 2010

Study Completion (ACTUAL)

June 1, 2010

Study Registration Dates

First Submitted

October 28, 2009

First Submitted That Met QC Criteria

October 28, 2009

First Posted (ESTIMATE)

October 29, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

August 19, 2013

Last Update Submitted That Met QC Criteria

August 15, 2013

Last Verified

August 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TRA-204

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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