Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01973504
Registration number
NCT01973504
Ethics application status
Date submitted
20/08/2013
Date registered
31/10/2013
Date last updated
31/10/2013
Titles & IDs
Public title
Phase 2c Dose Comparison Study of MP4OX in Trauma
Query!
Scientific 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
Query!
Secondary ID [1]
0
0
TRA-207
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Trauma
0
0
Query!
Hemorrhagic Shock
0
0
Query!
Lactic Acidosis
0
0
Query!
Condition category
Condition code
Metabolic and Endocrine
0
0
0
0
Query!
Other metabolic disorders
Query!
Respiratory
0
0
0
0
Query!
Other respiratory disorders / diseases
Query!
Renal and Urogenital
0
0
0
0
Query!
Kidney disease
Query!
Metabolic and Endocrine
0
0
0
0
Query!
Metabolic disorders
Query!
Cardiovascular
0
0
0
0
Query!
Diseases of the vasculature and circulation including the lymphatic system
Query!
Cardiovascular
0
0
0
0
Query!
Other cardiovascular diseases
Query!
Blood
0
0
0
0
Query!
Other blood disorders
Query!
Skin
0
0
0
0
Query!
Other skin conditions
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - MP4OX
Treatment: Drugs - Control
Experimental: MP4OX 500-mL - 500-mL dose of MP4OX
Experimental: MP4OX 750-mL - 750-mL dose of MP4OX
Sham Comparator: Control - Standard crystalloid Keep Vein Open (KVO) infusion
Treatment: Drugs: MP4OX
4.3 g/dL pegylated hemoglobin in balanced lactate-electrolyte solution
Treatment: Drugs: Control
Crystalloid solution IV infusion drip to keep vein open
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Proportion of subjects discharged from hospital through Day 28 and alive at the Day 28 Follow up visit
Query!
Assessment method [1]
0
0
Query!
Timepoint [1]
0
0
28 days
Query!
Secondary outcome [1]
0
0
Hospital-free, ICU-free, and Ventilator-free days
Query!
Assessment method [1]
0
0
Query!
Timepoint [1]
0
0
Through 28 and 60 days
Query!
Secondary outcome [2]
0
0
Proportion of subjects remaining in hospital, ICU or on ventilator
Query!
Assessment method [2]
0
0
Query!
Timepoint [2]
0
0
Through 28 and 60 days
Query!
Secondary outcome [3]
0
0
Days in hospital, in ICU, or on Ventilator
Query!
Assessment method [3]
0
0
Query!
Timepoint [3]
0
0
Through 28 and 60 days
Query!
Secondary outcome [4]
0
0
All-cause Mortality
Query!
Assessment method [4]
0
0
Query!
Timepoint [4]
0
0
At 48 hours and 28 or 60 days
Query!
Secondary outcome [5]
0
0
Time to discharge from ICU, hospital discharge, or liberation from ventilation
Query!
Assessment method [5]
0
0
Query!
Timepoint [5]
0
0
Through 28 or 60 days
Query!
Secondary outcome [6]
0
0
Composite of Time to Complete Organ Failure Resolution (CTCOFR)
Query!
Assessment method [6]
0
0
Query!
Timepoint [6]
0
0
Day 21
Query!
Eligibility
Key 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)
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key 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
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Withdrawn
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
1/12/2013
Query!
Actual
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
1/03/2016
Query!
Actual
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
0
Query!
Recruitment in Australia
Recruitment state(s)
Query!
Recruitment hospital [1]
0
0
Liverpool Hospital - Liverpool
Query!
Recruitment hospital [2]
0
0
John Hunter Hospital - Newcastle
Query!
Recruitment postcode(s) [1]
0
0
- Liverpool
Query!
Recruitment postcode(s) [2]
0
0
- Newcastle
Query!
Recruitment outside Australia
Country [1]
0
0
Belgium
Query!
State/province [1]
0
0
Brussels
Query!
Country [2]
0
0
Belgium
Query!
State/province [2]
0
0
Edegem
Query!
Country [3]
0
0
Brazil
Query!
State/province [3]
0
0
São José do Rio Preto
Query!
Country [4]
0
0
Brazil
Query!
State/province [4]
0
0
São Paulo
Query!
Country [5]
0
0
France
Query!
State/province [5]
0
0
Clichy
Query!
Country [6]
0
0
France
Query!
State/province [6]
0
0
Le Kremlin Bicêtre Cedex
Query!
Country [7]
0
0
France
Query!
State/province [7]
0
0
Lille Cedex
Query!
Country [8]
0
0
France
Query!
State/province [8]
0
0
Limoges
Query!
Country [9]
0
0
France
Query!
State/province [9]
0
0
Lyon
Query!
Country [10]
0
0
France
Query!
State/province [10]
0
0
Paris Cedex
Query!
Country [11]
0
0
Germany
Query!
State/province [11]
0
0
Aachen
Query!
Country [12]
0
0
Germany
Query!
State/province [12]
0
0
Berlin
Query!
Country [13]
0
0
Germany
Query!
State/province [13]
0
0
Cologne
Query!
Country [14]
0
0
Germany
Query!
State/province [14]
0
0
Franfurt
Query!
Country [15]
0
0
Germany
Query!
State/province [15]
0
0
Ludwigshafen
Query!
Country [16]
0
0
Israel
Query!
State/province [16]
0
0
Be'er-Sheva
Query!
Country [17]
0
0
Israel
Query!
State/province [17]
0
0
Haifa
Query!
Country [18]
0
0
Israel
Query!
State/province [18]
0
0
Jerusalem
Query!
Country [19]
0
0
New Zealand
Query!
State/province [19]
0
0
Auckland
Query!
Country [20]
0
0
Norway
Query!
State/province [20]
0
0
Oslo
Query!
Country [21]
0
0
South Africa
Query!
State/province [21]
0
0
Alberton
Query!
Country [22]
0
0
South Africa
Query!
State/province [22]
0
0
Cape Town
Query!
Country [23]
0
0
South Africa
Query!
State/province [23]
0
0
Johannesburg
Query!
Country [24]
0
0
South Africa
Query!
State/province [24]
0
0
Soweto
Query!
Country [25]
0
0
Switzerland
Query!
State/province [25]
0
0
Lausanne
Query!
Country [26]
0
0
Switzerland
Query!
State/province [26]
0
0
Zurich
Query!
Country [27]
0
0
United Kingdom
Query!
State/province [27]
0
0
London
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Sangart
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
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.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT01973504
Query!
Trial related presentations / publications
Cole RH, Vandegriff KD. MP4, a vasodilatory PEGylated hemoglobin. Adv Exp Med Biol. 2011;701:85-90. doi: 10.1007/978-1-4419-7756-4_12.
Young MA, Lohman J, Malavalli A, Vandegriff KD, Winslow RM. Hemospan improves outcome in a model of perioperative hemodilution and blood loss in the rat: comparison with hydroxyethyl starch. J Cardiothorac Vasc Anesth. 2009 Jun;23(3):339-47. doi: 10.1053/j.jvca.2008.08.006. Epub 2008 Oct 22.
Vandegriff KD, Winslow RM. Hemospan: design principles for a new class of oxygen therapeutic. Artif Organs. 2009 Feb;33(2):133-8. doi: 10.1111/j.1525-1594.2008.00697.x.
Vandegriff KD, Malavalli A, Mkrtchyan GM, Spann SN, Baker DA, Winslow RM. Sites of modification of hemospan, a poly(ethylene glycol)-modified human hemoglobin for use as an oxygen therapeutic. Bioconjug Chem. 2008 Nov 19;19(11):2163-70. doi: 10.1021/bc8002666.
Svergun DI, Ekstrom F, Vandegriff KD, Malavalli A, Baker DA, Nilsson C, Winslow RM. Solution structure of poly(ethylene) glycol-conjugated hemoglobin revealed by small-angle X-ray scattering: implications for a new oxygen therapeutic. Biophys J. 2008 Jan 1;94(1):173-81. doi: 10.1529/biophysj.107.114314. Epub 2007 Sep 7.
Cole RH, Vandegriff KD, Szeri AJ, Savas O, Baker DA, Winslow RM. A quantitative framework for the design of acellular hemoglobins as blood substitutes: implications of dynamic flow conditions. Biophys Chem. 2007 Jun;128(1):63-74. doi: 10.1016/j.bpc.2007.03.004. Epub 2007 Mar 13.
Young MA, Riddez L, Kjellstrom BT, Bursell J, Winslow F, Lohman J, Winslow RM. MalPEG-hemoglobin (MP4) improves hemodynamics, acid-base status, and survival after uncontrolled hemorrhage in anesthetized swine. Crit Care Med. 2005 Aug;33(8):1794-804. doi: 10.1097/01.ccm.0000172648.55309.13.
Drobin D, Kjellstrom BT, Malm E, Malavalli A, Lohman J, Vandegriff KD, Young MA, Winslow RM. Hemodynamic response and oxygen transport in pigs resuscitated with maleimide-polyethylene glycol-modified hemoglobin (MP4). J Appl Physiol (1985). 2004 May;96(5):1843-53. doi: 10.1152/japplphysiol.00530.2003. Epub 2004 Jan 16.
Winslow RM, Lohman J, Malavalli A, Vandegriff KD. Comparison of PEG-modified albumin and hemoglobin in extreme hemodilution in the rat. J Appl Physiol (1985). 2004 Oct;97(4):1527-34. doi: 10.1152/japplphysiol.00404.2004. Epub 2004 Jun 18.
Vandegriff KD, Bellelli A, Samaja M, Malavalli A, Brunori M, Winslow RM. Kinetics of NO and O2 binding to a maleimide poly(ethylene glycol)-conjugated human haemoglobin. Biochem J. 2004 Aug 15;382(Pt 1):183-9. doi: 10.1042/BJ20040156.
Tsai AG, Vandegriff KD, Intaglietta M, Winslow RM. Targeted O2 delivery by low-P50 hemoglobin: a new basis for O2 therapeutics. Am J Physiol Heart Circ Physiol. 2003 Oct;285(4):H1411-9. doi: 10.1152/ajpheart.00307.2003. Epub 2003 Jun 12.
Vandegriff KD, Malavalli A, Wooldridge J, Lohman J, Winslow RM. MP4, a new nonvasoactive PEG-Hb conjugate. Transfusion. 2003 Apr;43(4):509-16. doi: 10.1046/j.1537-2995.2003.00341.x.
McCarthy MR, Vandegriff KD, Winslow RM. The role of facilitated diffusion in oxygen transport by cell-free hemoglobins: implications for the design of hemoglobin-based oxygen carriers. Biophys Chem. 2001 Aug 30;92(1-2):103-17. doi: 10.1016/s0301-4622(01)00194-6.
Young MA, Riddez L, Kjellstrom BT, Winslow RM. Effect of maleimide-polyethylene glycol hemoglobin (MP4) on hemodynamics and acid-base status after uncontrolled hemorrhage in anesthetized swine: comparison with crystalloid and blood. J Trauma. 2007 Dec;63(6):1234-44. doi: 10.1097/TA.0b013e31815bd7b0.
Wettstein R, Tsai AG, Erni D, Winslow RM, Intaglietta M. Resuscitation with polyethylene glycol-modified human hemoglobin improves microcirculatory blood flow and tissue oxygenation after hemorrhagic shock in awake hamsters. Crit Care Med. 2003 Jun;31(6):1824-30. doi: 10.1097/01.CCM.0000069340.16319.F2.
Husain FA, Martin MJ, Mullenix PS, Steele SR, Elliott DC. Serum lactate and base deficit as predictors of mortality and morbidity. Am J Surg. 2003 May;185(5):485-91. doi: 10.1016/s0002-9610(03)00044-8.
Regnier MA, Raux M, Le Manach Y, Asencio Y, Gaillard J, Devilliers C, Langeron O, Riou B. Prognostic significance of blood lactate and lactate clearance in trauma patients. Anesthesiology. 2012 Dec;117(6):1276-88. doi: 10.1097/ALN.0b013e318273349d.
McNelis J, Marini CP, Jurkiewicz A, Szomstein S, Simms HH, Ritter G, Nathan IM. Prolonged lactate clearance is associated with increased mortality in the surgical intensive care unit. Am J Surg. 2001 Nov;182(5):481-5. doi: 10.1016/s0002-9610(01)00755-3.
Abramson D, Scalea TM, Hitchcock R, Trooskin SZ, Henry SM, Greenspan J. Lactate clearance and survival following injury. J Trauma. 1993 Oct;35(4):584-8; discussion 588-9. doi: 10.1097/00005373-199310000-00014.
Tsai AG, Cabrales P, Manjula BN, Acharya SA, Winslow RM, Intaglietta M. Dissociation of local nitric oxide concentration and vasoconstriction in the presence of cell-free hemoglobin oxygen carriers. Blood. 2006 Nov 15;108(10):3603-10. doi: 10.1182/blood-2006-02-005272. Epub 2006 Jul 20.
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Karim Brohi, MD
Query!
Address
0
0
The Royal London Hospital
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01973504
Download to PDF