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Phase 2c Dose Comparison Study of MP4OX in Trauma

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ClinicalTrials.gov Identifier: NCT01973504
Recruitment Status : Withdrawn (Sangart ceased operations)
First Posted : October 31, 2013
Last Update Posted : October 31, 2013
Sponsor:
Information provided by (Responsible Party):
Sangart

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Trauma Hemorrhagic Shock Lactic Acidosis Drug: MP4OX Drug: Control Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : December 2013
Estimated Primary Completion Date : December 2015
Estimated Study Completion Date : March 2016

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Proportion of subjects discharged from hospital through Day 28 and alive at the Day 28 Follow up visit [ Time Frame: 28 days ]

Secondary Outcome Measures :
  1. Hospital-free, ICU-free, and Ventilator-free days [ Time Frame: Through 28 and 60 days ]
  2. Proportion of subjects remaining in hospital, ICU or on ventilator [ Time Frame: Through 28 and 60 days ]
  3. Days in hospital, in ICU, or on Ventilator [ Time Frame: Through 28 and 60 days ]
  4. All-cause Mortality [ Time Frame: At 48 hours and 28 or 60 days ]
  5. Time to discharge from ICU, hospital discharge, or liberation from ventilation [ Time Frame: Through 28 or 60 days ]
  6. Composite of Time to Complete Organ Failure Resolution (CTCOFR) [ Time Frame: Day 21 ]

Other Outcome Measures:
  1. Daily modified Denver Score [ Time Frame: Day 7 ]
  2. Proportion of patients with persistent renal dysfunction [ Time Frame: Day 60 ]
  3. Duration of ICU stay for survivors [ Time Frame: Day 28 and Day 60 ]
  4. Proportion of subjects who normalize lactate [ Time Frame: 4 hours ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01973504


  Show 31 Study Locations
Sponsors and Collaborators
Sangart
Investigators
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Principal Investigator: Karim Brohi, MD The Royal London Hospital
Study Chair: Frank V. Booth, BCh, FACS Sangart, Inc.

Additional Information:
Publications:

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Responsible Party: Sangart
ClinicalTrials.gov Identifier: NCT01973504     History of Changes
Other Study ID Numbers: TRA-207
First Posted: October 31, 2013    Key Record Dates
Last Update Posted: October 31, 2013
Last Verified: October 2013

Keywords provided by Sangart:
Trauma
Hemorrhagic shock
Hemorrhage
Lactic acidosis
Oxygen therapeutics
Oxygen carriers
Ischemic rescue therapy
Hemoglobin solutions
PEGylated hemoglobin

Additional relevant MeSH terms:
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Acidosis
Acidosis, Lactic
Shock
Shock, Hemorrhagic
Wounds and Injuries
Pathologic Processes
Acid-Base Imbalance
Metabolic Diseases
Hemorrhage
Pharmaceutical Solutions