Clinical trial NCT01973504: Phase 2c Dose Comparison Study of MP4OX in Trauma
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 type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Trauma
Hemorrhagic Shock
Lactic Acidosis
Keywords: Trauma
Hemorrhagic shock
Hemorrhage
Lactic acidosis
Oxygen therapeutics
Oxygen carriers
Ischemic rescue therapy
Hemoglobin solutions
PEGylated hemoglobin
Lead sponsor: Sangart
Sponsor class: INDUSTRY
First posted: 2013-10-31
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Proportion of subjects discharged from hospital through Day 28 and alive at the Day 28 Follow up visit
timeFrame: 28 days
Secondary outcomes:
measure: Hospital-free, ICU-free, and Ventilator-free days
timeFrame: Through 28 and 60 days
measure: Proportion of subjects remaining in hospital, ICU or on ventilator
timeFrame: Through 28 and 60 days
measure: Days in hospital, in ICU, or on Ventilator
timeFrame: Through 28 and 60 days
measure: All-cause Mortality
timeFrame: At 48 hours and 28 or 60 days
measure: Time to discharge from ICU, hospital discharge, or liberation from ventilation
timeFrame: Through 28 or 60 days
measure: Composite of Time to Complete Organ Failure Resolution (CTCOFR)
timeFrame: Day 21
Other outcomes:
measure: Daily modified Denver Score
timeFrame: Day 7
measure: Proportion of patients with persistent renal dysfunction
timeFrame: Day 60
measure: Duration of ICU stay for survivors
timeFrame: Day 28 and Day 60
measure: Proportion of subjects who normalize lactate
timeFrame: 4 hours
Locations:
city: Liverpool
country: Australia
facility: Liverpool Hospital
city: Newcastle
country: Australia
facility: John Hunter Hospital
city: Brussels
country: Belgium
facility: Erasme University Hospital
city: Edegem
country: Belgium
facility: University Hospital Antwerpen
city: São José do Rio Preto
country: Brazil
facility: Faculdade de Medicina de S. J. Do Rio Preto
city: São Paulo
country: Brazil
facility: Hopital Universitário, Centro de Estudos em Emergências em Saúde, USP Ribeirão Preto
city: São Paulo
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo - FMUSP
city: Clichy
country: France
facility: Hôpital Beaujon
city: Le Kremlin Bicêtre Cedex
country: France
facility: Hôpital du Kremlin Bicêtre
city: Lille Cedex
country: France
facility: Hôpital Roger Salengro, CHRU Lille
city: Limoges
country: France
facility: CHU Dupuytren
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Paris Cedex
country: France
facility: Hôpital Pitié-Salpêtrière
city: Aachen
country: Germany
facility: Universitätsklinikum der Rheinisch-Westfälische Technische Hochschule Aachen
city: Berlin
country: Germany
facility: Campus Virchow Klinikum Charité Berlin
city: Cologne
country: Germany
facility: Kliniken der Stadt Köln gGmbH Krankenhaus Merheim
city: Franfurt
country: Germany
facility: Klinikum der J.-W.-Goethe-Universität Frankfurt a.M.
city: Ludwigshafen
country: Germany
facility: BG Klinik Ludwigshafen
city: Be'er-Sheva
country: Israel
facility: Soroka University Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Hadassah Medical Organization, Hadassah University Hospital, Ein-Karem
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital Ullevaal
city: Alberton
country: South Africa
facility: Netcare Union Hospital
city: Cape Town
country: South Africa
facility: Vincent Palotti Dr Christiaan Barnard Memorial Hospital
city: Johannesburg
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospita
city: Johannesburg
country: South Africa
facility: Netcare Milpark Hospital
city: Soweto
country: South Africa
facility: Chris Hani Baragwanath Hospital
city: Lausanne
country: Switzerland
facility: CHU Vaudois
city: Zurich
country: Switzerland
facility: UniversitätsSpital Zürich
city: London
country: United Kingdom
facility: The Royal London Hospital
Study officials:
affiliation: The Royal London Hospital
name: Karim Brohi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sangart, Inc.
name: Frank V. Booth, BCh, FACS
role: STUDY_CHAIR
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