Phase IIa Study of MP4OX in Traumatic Hemorrhagic Shock Patients

Sponsor

Sangart (Industry)

Overall Status

Completed

CT.gov ID

NCT01004198

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

3.9

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Shock, Hemorrhagic Shock, Traumatic Acidosis, Lactic	Drug: MP4OX Drug: MP4OX Drug: Ringers Lactate solution	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

51 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Study Start Date :

Dec 1, 2009

Actual Primary Completion Date :

Jun 1, 2010

Actual Study Completion Date :

Jun 1, 2010

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: MP4OX - 250

250 mL dose

Drug: MP4OX

4.3 g/dL PEG-Hb solution in lactated electrolyte solution

Other Names:

MP4

MalPEG-Hb

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:

MP4

MalPEG-Hb

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

Outcome Measures

Primary Outcome Measures

Serum lactate clearance [2 hours]

Secondary Outcome Measures

All-cause mortality [28 days]
Ventilator-free days [28 days]
ICU-free days [28 days]
Hospital-free days [28 days]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country
1	Centre Hospitalier de Bicêtre	Le Kremlin Bicetre	France
2	CHRU de Lille - Hôpital Claude Huriez	Lille	France
3	Hôpital Dupuytren	Limoges	France
4	Hôpital Pitié-Salpêtrière	Paris	France
5	Charité Campus Virchow Klinikum	Berlin	Germany
6	Klinikum der Johann-Wolfgang-Goethe-Universität	Frankfurt	Germany
7	Netcare Union Hospital	Alberton	South Africa
8	Charlotte Maxeke Johannesburg Hospital	Johannesburg	South Africa
9	Netcare Milpark Hospital	Johannesburg	South Africa
10	Netcare Unitas Hospital, Centurian	Pretoria	South Africa
11	Steve Biko Academic Hospital	Pretoria	South Africa
12	Chris Hani Baragwanath Hospital	Soweto	South Africa
13	The Royal London Hospital	London	United Kingdom