Phase 2c Dose Comparison Study of MP4OX in Trauma

October 25, 2013 updated by: Sangart

A Multi-center, Multinational, Randomized, Double-blind, Controlled, Dose Comparison Study to Evaluate Safety and Efficacy of MP4OX Plus Standard Treatment, in Severely Injured Trauma Subjects With Lactic Acidosis Due to Hemorrhagic Shock

MP4OX is being developed as an ischemic rescue therapy to perfuse and oxygenate tissues at risk during hemorrhagic shock. MP4OX is a pegylated hemoglobin-based colloid designed to improve perfusion and target delivery of oxygen to ischemic tissues. This study will evaluate safety and efficacy of MP4OX treatment, in addition to standard therapy, in trauma patients suffering from lactic acidosis due to severe hemorrhagic shock.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Acute trauma, including both blunt and penetrating injury, is often associated with uncontrolled bleeding that leads to hemorrhagic shock. During shock, inadequate blood flow results in local ischemia and tissue hypoxia (insufficient oxygenation) of critical organs with resulting lactic acidosis. More than 10% of trauma victims who reach hospital alive will die, and many will suffer from organ failure. The primary goal when treating traumatic hemorrhage is to control blood loss, support ventilation and oxygenation, and maintain cardiovascular function to maintain organ perfusion.

Despite optimal care, organ dysfunction is present in many patients as evidenced by persistent lactic acidosis. Blood transfusions are intended to improve circulation of oxygen-carrying red blood cells, but are frequently insufficient, even when the hemoglobin level is optimized. The severity of lactic acidosis in trauma victims has also been shown to correlate with worse outcome.

Support for the proposed application for MP4OX as a therapeutic adjunct to standard treatment of severe hemorrhage shock, is based on multiple preclinical studies in different animal models of hemorrhagic shock resuscitation. These preclinical studies demonstrated that survival was greater and restoration of acid-base status and hemodynamics were improved with MP4OX. The benefits of MP4OX in animals were observed with or without co-administration of autologous blood, demonstrating that red cell transfusion alone was insufficient, and that the effects of MP4OX were additive.

The hypothesis for the current study is that MP4OX will enhance perfusion and oxygenation of ischemic organs and thereby prevent and reduce the duration of organ failure and improve morbidity and mortality outcome measures.

Study Type

Interventional

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

  • Australia
      • Liverpool, Australia
        • Liverpool Hospital
      • Newcastle, Australia
        • John Hunter Hospital
  • Belgium
      • Brussels, Belgium
        • Erasme University Hospital
      • Edegem, Belgium
        • University Hospital Antwerpen
  • Brazil
      • São José do Rio Preto, Brazil
        • Faculdade de Medicina de S. J. Do Rio Preto
      • São Paulo, Brazil
        • Hopital Universitário, Centro de Estudos em Emergências em Saúde, USP Ribeirão Preto
      • São Paulo, Brazil
        • Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo - FMUSP
  • France
      • Clichy, France
        • Hopital Beaujon
      • Le Kremlin Bicêtre Cedex, France
        • Hôpital du Kremlin Bicetre
      • Lille Cedex, France
        • Hôpital Roger Salengro, CHRU Lille
      • Limoges, France
        • Chu Dupuytren
      • Lyon, France
        • Hôpital Edouard Herriot
      • Paris Cedex, France
        • Hôpital Pitié-Salpétrière
  • Germany
      • Aachen, Germany
        • Universitätsklinikum der Rheinisch-Westfälische Technische Hochschule Aachen
      • Berlin, Germany
        • Campus Virchow Klinikum Charité Berlin
      • Cologne, Germany
        • Kliniken der Stadt Köln gGmbH Krankenhaus Merheim
      • Franfurt, Germany
        • Klinikum der J.-W.-Goethe-Universität Frankfurt a.M.
      • Ludwigshafen, Germany
        • BG Klinik Ludwigshafen
  • Israel
      • Be'er-Sheva, Israel
        • Soroka University Medical Center
      • Haifa, Israel
        • Rambam Health Care Campus
      • Jerusalem, Israel
        • Hadassah Medical Organization, Hadassah University Hospital, Ein-Karem
  • New Zealand
      • Auckland, New Zealand
        • Auckland City Hospital
  • Norway
      • Oslo, Norway
        • Oslo University Hospital Ullevaal
  • South Africa
      • Alberton, South Africa
        • Netcare Union Hospital
      • Cape Town, South Africa
        • Vincent Palotti Dr Christiaan Barnard Memorial Hospital
      • Johannesburg, South Africa
        • Charlotte Maxeke Johannesburg Academic Hospita
      • Johannesburg, South Africa
        • Netcare Milpark Hospital
      • Soweto, South Africa
        • Chris Hani Baragwanath Hospital
  • Switzerland
      • Lausanne, Switzerland
        • CHU vaudois
      • Zurich, Switzerland
        • UniversitätsSpital Zürich
  • 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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Trauma injury (blunt and/or penetrating) resulting in lactic acidosis due to hemorrhagic shock
  • Acidosis (blood lactate level ≥ 5 mmol/L; equivalent to 45 mg/dL)

Exclusion Criteria:

  • Massive injury incompatible with life
  • Normalization of lactate prior to dosing (≤ 2.2 mmol/L)
  • Evidence of severe traumatic brain injury (TBI) as defined by ANY one of the following: Known non-survivable head injury or open brain injury; Known AIS (head region) ≥ 4 by an appropriate imaging methodology; Contemplated CNS surgery; Abnormal physical exam indicative of severe CNS or any spinal cord injury above T5 level; or Glasgow Coma Score (GCS) = 3, 4 or 5.
  • Cardiac arrest prior to randomization
  • Known age below the legal age for consenting
  • Estimated time from injury to randomization > 4 hours
  • Estimated time from hospital admission to randomization > 2 hours
  • Known pregnancy
  • Use of any oxygen carrier other than RBCs
  • Known previous participation in this study
  • Professional or ancillary personnel involved with this study
  • Known 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 Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MP4OX 500-mL
500-mL dose of MP4OX
Drug: MP4OX
4.3 g/dL pegylated hemoglobin in balanced lactate-electrolyte solution
Other Names:
  • Hemoglobin pegylated
  • MalPEG-Hb
  • MP4
  • PEG-Hb
  • Pegylated-Hb
Experimental: MP4OX 750-mL
750-mL dose of MP4OX
Drug: MP4OX
4.3 g/dL pegylated hemoglobin in balanced lactate-electrolyte solution
Other Names:
  • Hemoglobin pegylated
  • MalPEG-Hb
  • MP4
  • PEG-Hb
  • Pegylated-Hb
Sham Comparator: Control
Standard crystalloid Keep Vein Open (KVO) infusion
Drug: Control
Crystalloid solution IV infusion drip to keep vein open
Other Names:
  • Keep vein open (KVO) infusion
  • Sham infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Proportion of subjects discharged from hospital through Day 28 and alive at the Day 28 Follow up visit
Time Frame: 28 days
28 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Hospital-free, ICU-free, and Ventilator-free days
Time Frame: Through 28 and 60 days
Through 28 and 60 days
Proportion of subjects remaining in hospital, ICU or on ventilator
Time Frame: Through 28 and 60 days
Through 28 and 60 days
Days in hospital, in ICU, or on Ventilator
Time Frame: Through 28 and 60 days
Through 28 and 60 days
All-cause Mortality
Time Frame: At 48 hours and 28 or 60 days
At 48 hours and 28 or 60 days
Time to discharge from ICU, hospital discharge, or liberation from ventilation
Time Frame: Through 28 or 60 days
Through 28 or 60 days
Composite of Time to Complete Organ Failure Resolution (CTCOFR)
Time Frame: Day 21
Day 21

Other Outcome Measures

Outcome Measure
Time Frame
Daily modified Denver Score
Time Frame: Day 7
Day 7
Proportion of patients with persistent renal dysfunction
Time Frame: Day 60
Day 60
Duration of ICU stay for survivors
Time Frame: Day 28 and Day 60
Day 28 and Day 60
Proportion of subjects who normalize lactate
Time Frame: 4 hours
4 hours

Collaborators and Investigators

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

Sponsor

Sangart

Investigators

  • Study Chair: Frank V. Booth, BCh, FACS, Sangart, Inc.

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, 2013

Primary Completion (Anticipated)

December 1, 2015

Study Completion (Anticipated)

March 1, 2016

Study Registration Dates

First Submitted

August 20, 2013

First Submitted That Met QC Criteria

October 25, 2013

First Posted (Estimate)

October 31, 2013

Study Record Updates

Last Update Posted (Estimate)

October 31, 2013

Last Update Submitted That Met QC Criteria

October 25, 2013

Last Verified

October 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TRA-207

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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