Phase 2c Dose Comparison Study of MP4OX in Trauma

Phase 2

Withdrawn

• Conditions: Trauma; Lactic Acidosis; Hemorrhagic Shock
• Interventions: Drug: MP4OX; Drug: Control

• Registration Number: NCT01973504
• Lead Sponsor: 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.

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 Timeline

• Study First Submitted: 2013-08-20
• Status Verified: 2013-10
• Study First Submitted QC: 2013-10-25
• Last Update Submitted: 2013-10-25
• Study First Posted: 2013-10-31
• Last Update Posted: 2013-10-31
• Study Start: 2013-12
• Primary Completion: 2015-12
• Study Completion: 2016-03

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MP4OX 750-mL	MP4OX	750-mL dose of MP4OX
Control	Control	Standard crystalloid Keep Vein Open (KVO) infusion
MP4OX 500-mL	MP4OX	500-mL dose of MP4OX

Primary Outcome Measures

Name	Time	Method
Proportion of subjects discharged from hospital through Day 28 and alive at the Day 28 Follow up visit	28 days

Secondary Outcome Measures

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

Trial Locations

Locations (31)

Erasme University Hospital; 🇧🇪 Brussels, Belgium

University Hospital Antwerpen; 🇧🇪 Edegem, Belgium

Soroka University Medical Center; 🇮🇱 Be'er-Sheva, Israel

Rambam Health Care Campus; 🇮🇱 Haifa, Israel

Hadassah Medical Organization, Hadassah University Hospital, Ein-Karem; 🇮🇱 Jerusalem, Israel

Oslo University Hospital Ullevaal; 🇳🇴 Oslo, Norway

CHU Vaudois; 🇨🇭 Lausanne, Switzerland

The Royal London Hospital; 🇬🇧 London, United Kingdom

CHU Dupuytren; 🇫🇷 Limoges, France

Auckland City Hospital; 🇳🇿 Auckland, New Zealand

Campus Virchow Klinikum Charité Berlin; 🇩🇪 Berlin, Germany

Chris Hani Baragwanath Hospital; 🇿🇦 Soweto, South Africa

BG Klinik Ludwigshafen; 🇩🇪 Ludwigshafen, Germany

Netcare Milpark Hospital; 🇿🇦 Johannesburg, South Africa

Hôpital Roger Salengro, CHRU Lille; 🇫🇷 Lille Cedex, France

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo - FMUSP; 🇧🇷 São Paulo, Brazil

Hôpital du Kremlin Bicêtre; 🇫🇷 Le Kremlin Bicêtre Cedex, France

Hôpital Pitié-Salpêtrière; 🇫🇷 Paris Cedex, France

Liverpool Hospital; 🇦🇺 Liverpool, Australia

Universitätsklinikum der Rheinisch-Westfälische Technische Hochschule Aachen; 🇩🇪 Aachen, Germany

Hôpital Beaujon; 🇫🇷 Clichy, France

Hôpital Edouard Herriot; 🇫🇷 Lyon, France

Klinikum der J.-W.-Goethe-Universität Frankfurt a.M.; 🇩🇪 Franfurt, Germany

Kliniken der Stadt Köln gGmbH Krankenhaus Merheim; 🇩🇪 Cologne, Germany

Faculdade de Medicina de S. J. Do Rio Preto; 🇧🇷 São José do Rio Preto, Brazil

John Hunter Hospital; 🇦🇺 Newcastle, Australia

Hopital Universitário, Centro de Estudos em Emergências em Saúde, USP Ribeirão Preto; 🇧🇷 São Paulo, Brazil

Netcare Union Hospital; 🇿🇦 Alberton, South Africa

Charlotte Maxeke Johannesburg Academic Hospita; 🇿🇦 Johannesburg, South Africa

Vincent Palotti Dr Christiaan Barnard Memorial Hospital; 🇿🇦 Cape Town, South Africa

UniversitätsSpital Zürich; 🇨🇭 Zurich, Switzerland