Phase IIa Study of MP4OX in Traumatic Hemorrhagic Shock Patients

Phase 2

Completed

• Conditions: Shock, Hemorrhagic; Shock, Traumatic; Acidosis, Lactic
• Interventions: Drug: MP4OX; Drug: Ringers Lactate solution

• Registration Number: NCT01004198
• Lead Sponsor: Sangart

Brief 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.

Study Timeline

• Study First Submitted: 2009-10-28
• Study First Submitted QC: 2009-10-28
• Study First Posted: 2009-10-29
• Study Start: 2009-12
• Primary Completion: 2010-06
• Study Completion: 2010-06
• Status Verified: 2013-08
• Last Update Submitted: 2013-08-15
• Last Update Posted: 2013-08-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 51

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MP4OX - 250	MP4OX	250 mL dose
MP4OX - 500	MP4OX	500 mL dose
Ringers Lactate solution	Ringers Lactate solution	500 mL dose

Primary Outcome Measures

Name	Time	Method
Serum lactate clearance	2 hours

Secondary Outcome Measures

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

Trial Locations

Locations (13)

Hôpital Pitié-Salpêtrière; 🇫🇷 Paris, France

Netcare Milpark Hospital; 🇿🇦 Johannesburg, South Africa

Centre Hospitalier de Bicêtre; 🇫🇷 Le Kremlin Bicetre, France

CHRU de Lille - Hôpital Claude Huriez; 🇫🇷 Lille, France

Charité Campus Virchow Klinikum; 🇩🇪 Berlin, Germany

Hôpital Dupuytren; 🇫🇷 Limoges, France

The Royal London Hospital; 🇬🇧 London, United Kingdom

Klinikum der Johann-Wolfgang-Goethe-Universität; 🇩🇪 Frankfurt, Germany

Netcare Union Hospital; 🇿🇦 Alberton, South Africa

Netcare Unitas Hospital, Centurian; 🇿🇦 Pretoria, South Africa

Steve Biko Academic Hospital; 🇿🇦 Pretoria, South Africa

Charlotte Maxeke Johannesburg Hospital; 🇿🇦 Johannesburg, South Africa

Chris Hani Baragwanath Hospital; 🇿🇦 Soweto, South Africa