Phase IIa Study of MP4OX in Traumatic Hemorrhagic Shock Patients
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Shock, Hemorrhagic Shock, Traumatic Acidosis, Lactic |
Drug: MP4OX Drug: Ringer's Lactate solution |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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 |
- Serum lactate clearance [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
- All-cause mortality [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- Ventilator-free days [ Time Frame: 28 days ] [ Designated as safety issue: No ]
- ICU-free days [ Time Frame: 28 days ] [ Designated as safety issue: No ]
- Hospital-free days [ Time Frame: 28 days ] [ Designated as safety issue: No ]
- Sepsis-related Organ Failure Assessment (SOFA) score [ Time Frame: Daily ] [ Designated as safety issue: Yes ]
- Modified Denver score [ Time Frame: Daily ] [ Designated as safety issue: Yes ]
- Composite endpoint of Time to Complete Organ Failure Resolution (CTCOFR) [ Time Frame: At 14 and 21 days ] [ Designated as safety issue: Yes ]
| Enrollment: | 51 |
| Study Start Date: | December 2009 |
| Study Completion Date: | June 2010 |
| Primary Completion Date: | June 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: MP4OX - 250
250 mL dose
|
Drug: MP4OX
4.3 g/dL PEG-Hb solution in lactated electrolyte solution
Other Names:
|
|
Experimental: MP4OX - 500
500 mL dose
|
Drug: MP4OX
4.3 g/dL PEG-Hb solution in lactated electrolyte solution
Other Names:
|
|
Placebo Comparator: R-L Control
500 mL of Ringer's Lactate solution
|
Drug: Ringer's Lactate solution
500 mL infusion
Other Names:
|
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.
Eligibility| Ages Eligible for Study: | 18 Years to 80 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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| France | |
| Centre Hospitalier de Bicêtre | |
| Le Kremlin Bicetre, France | |
| CHRU de Lille - Hôpital Claude Huriez | |
| Lille, France | |
| Hôpital Dupuytren | |
| Limoges, France | |
| Hôpital Pitié-Salpêtrière | |
| Paris, France | |
| Germany | |
| Charité Campus Virchow Klinikum | |
| Berlin, Germany | |
| Klinikum der Johann-Wolfgang-Goethe-Universität | |
| Frankfurt, Germany | |
| South Africa | |
| Netcare Union Hospital | |
| Alberton, South Africa | |
| Netcare Milpark Hospital | |
| Johannesburg, South Africa | |
| Charlotte Maxeke Johannesburg Hospital | |
| Johannesburg, South Africa | |
| Steve Biko Academic Hospital | |
| Pretoria, South Africa | |
| Netcare Unitas Hospital, Centurian | |
| Pretoria, South Africa | |
| Chris Hani Baragwanath Hospital | |
| Soweto, South Africa | |
| United Kingdom | |
| The Royal London Hospital | |
| London, United Kingdom | |
| Study Director: | Howard Levy, MD, PhD | Sangart, Inc. (San Diego, CA) |
More Information
Additional Information:
Publications:
| Responsible Party: | Sangart |
| ClinicalTrials.gov Identifier: | NCT01004198 History of Changes |
| Other Study ID Numbers: | TRA-204 |
| Study First Received: | October 28, 2009 |
| Last Updated: | August 30, 2011 |
| Health Authority: | South Africa: Medicines Control Council United Kingdom: Medicines and Healthcare Products Regulatory Agency France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Paul-Ehrlich-Institut |
Keywords provided by Sangart:
|
Trauma Hemorrhage Hemorrhagic shock Lactic acidosis Oxygen carriers |
Oxygen therapeutics Hemoglobin solutions Hemoglobin substitutes Red cell substitutes PEG-hemoglobin |
Additional relevant MeSH terms:
|
Acidosis Acidosis, Lactic Shock Shock, Hemorrhagic Shock, Traumatic Acid-Base Imbalance Metabolic Diseases |
Pathologic Processes Hemorrhage Wounds and Injuries Blood Substitutes Hematologic Agents Therapeutic Uses Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 16, 2013