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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
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
Secondary ID [1] 0 0
TRA-207
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Trauma 0 0
Hemorrhagic Shock 0 0
Lactic Acidosis 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Renal and Urogenital 0 0 0 0
Kidney disease
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Blood 0 0 0 0
Other blood disorders
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of subjects discharged from hospital through Day 28 and alive at the Day 28 Follow up visit
Timepoint [1] 0 0
28 days
Secondary outcome [1] 0 0
Hospital-free, ICU-free, and Ventilator-free days
Timepoint [1] 0 0
Through 28 and 60 days
Secondary outcome [2] 0 0
Proportion of subjects remaining in hospital, ICU or on ventilator
Timepoint [2] 0 0
Through 28 and 60 days
Secondary outcome [3] 0 0
Days in hospital, in ICU, or on Ventilator
Timepoint [3] 0 0
Through 28 and 60 days
Secondary outcome [4] 0 0
All-cause Mortality
Timepoint [4] 0 0
At 48 hours and 28 or 60 days
Secondary outcome [5] 0 0
Time to discharge from ICU, hospital discharge, or liberation from ventilation
Timepoint [5] 0 0
Through 28 or 60 days
Secondary outcome [6] 0 0
Composite of Time to Complete Organ Failure Resolution (CTCOFR)
Timepoint [6] 0 0
Day 21

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)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
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
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/12/2013
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2016
Actual
Sample size
Target
Accrual to date
Final
0
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
John Hunter Hospital - Newcastle
Recruitment postcode(s) [1] 0 0
- Liverpool
Recruitment postcode(s) [2] 0 0
- Newcastle
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Brussels
Country [2] 0 0
Belgium
State/province [2] 0 0
Edegem
Country [3] 0 0
Brazil
State/province [3] 0 0
São José do Rio Preto
Country [4] 0 0
Brazil
State/province [4] 0 0
São Paulo
Country [5] 0 0
France
State/province [5] 0 0
Clichy
Country [6] 0 0
France
State/province [6] 0 0
Le Kremlin Bicêtre Cedex
Country [7] 0 0
France
State/province [7] 0 0
Lille Cedex
Country [8] 0 0
France
State/province [8] 0 0
Limoges
Country [9] 0 0
France
State/province [9] 0 0
Lyon
Country [10] 0 0
France
State/province [10] 0 0
Paris Cedex
Country [11] 0 0
Germany
State/province [11] 0 0
Aachen
Country [12] 0 0
Germany
State/province [12] 0 0
Berlin
Country [13] 0 0
Germany
State/province [13] 0 0
Cologne
Country [14] 0 0
Germany
State/province [14] 0 0
Franfurt
Country [15] 0 0
Germany
State/province [15] 0 0
Ludwigshafen
Country [16] 0 0
Israel
State/province [16] 0 0
Be'er-Sheva
Country [17] 0 0
Israel
State/province [17] 0 0
Haifa
Country [18] 0 0
Israel
State/province [18] 0 0
Jerusalem
Country [19] 0 0
New Zealand
State/province [19] 0 0
Auckland
Country [20] 0 0
Norway
State/province [20] 0 0
Oslo
Country [21] 0 0
South Africa
State/province [21] 0 0
Alberton
Country [22] 0 0
South Africa
State/province [22] 0 0
Cape Town
Country [23] 0 0
South Africa
State/province [23] 0 0
Johannesburg
Country [24] 0 0
South Africa
State/province [24] 0 0
Soweto
Country [25] 0 0
Switzerland
State/province [25] 0 0
Lausanne
Country [26] 0 0
Switzerland
State/province [26] 0 0
Zurich
Country [27] 0 0
United Kingdom
State/province [27] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sangart
Address
Country

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/study/NCT01973504
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.
Public notes

Contacts
Principal investigator
Name 0 0
Karim Brohi, MD
Address 0 0
The Royal London Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01973504