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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01262196




Registration number
NCT01262196
Ethics application status
Date submitted
15/12/2010
Date registered
17/12/2010
Date last updated
22/08/2013

Titles & IDs
Public title
Phase IIb Study of MP4OX in Traumatic Hemorrhagic Shock Patients
Scientific title
A Multi-center, Randomized, Double-blind, Controlled Study to Evaluate the Safety and Efficacy of MP4OX Treatment, in Addition to Standard Treatment, in Severely Injured Trauma Patients With Lactic Acidosis Due to Hemorrhagic Shock
Secondary ID [1] 0 0
TRA-205
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Shock, Hemorrhagic 0 0
Shock, Traumatic 0 0
Acidosis, Lactic 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
Injuries and Accidents 0 0 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MP4OX
Treatment: Drugs - Saline

Experimental: MP4OX - 250-mL dose

Placebo comparator: Control - 250-mL of normal saline solution


Treatment: Drugs: MP4OX
4.3 g/dL pegylated hemoglobin in balanced lactate-electrolyte solution

Treatment: Drugs: Saline
Normal saline (0.9%) solution
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of patients 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 days
Secondary outcome [2] 0 0
Composite endpoint of Time to Complete Organ Failure Resolution (CTCOFR)
Timepoint [2] 0 0
At 14 and 21 days
Secondary outcome [3] 0 0
Proportion of patients who normalize (= 2.2 mmol/L) lactate levels
Timepoint [3] 0 0
2, 4, 6, 8 and 12 hours
Secondary outcome [4] 0 0
Proportion of patients remaining: (1) in hospital, (2) in ICU, and (3) on ventilator through Day 28
Timepoint [4] 0 0
28 days
Secondary outcome [5] 0 0
Number of days: (1) in hospital, (2) in ICU, and (3) on the ventilator
Timepoint [5] 0 0
Through 28 days
Secondary outcome [6] 0 0
All-cause mortality
Timepoint [6] 0 0
At 48 hours and at 28 days
Secondary outcome [7] 0 0
Time (days) from randomization to: (1) death, (2) discharge from hospital, (3) discharge from ICU, and (4) liberation from mechanical ventilation
Timepoint [7] 0 0
Through 28 days
Secondary outcome [8] 0 0
Sequential organ failure assessment (SOFA score)
Timepoint [8] 0 0
Daily
Secondary outcome [9] 0 0
Modified Denver score
Timepoint [9] 0 0
Daily

Eligibility
Key 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
* Acidosis (blood lactate level = 5 mmol/L; equivalent to 45 mg/dL) arterial or venous
Minimum age
No limit
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)
* Patients with 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; Known AIS (head region) = 4 shown by an appropriate imaging methodology; Contemplated CNS surgery; or Abnormal physical exam indicative of severe CNS or any spinal cord injury above T5 level
* Cardiac arrest prior to randomization
* 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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/11/2012
Sample size
Target
Accrual to date
Final
348
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Liverpoool Hospital NSW - 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
Austria
State/province [1] 0 0
Gratz
Country [2] 0 0
Brazil
State/province [2] 0 0
Sao Paolo
Country [3] 0 0
Brazil
State/province [3] 0 0
São José do Rio Preto
Country [4] 0 0
Colombia
State/province [4] 0 0
Cali
Country [5] 0 0
France
State/province [5] 0 0
Clichy
Country [6] 0 0
France
State/province [6] 0 0
Grenoble
Country [7] 0 0
France
State/province [7] 0 0
Le Kremlin Bicetre
Country [8] 0 0
France
State/province [8] 0 0
Lille
Country [9] 0 0
France
State/province [9] 0 0
Limoges
Country [10] 0 0
France
State/province [10] 0 0
Lyon
Country [11] 0 0
France
State/province [11] 0 0
Paris
Country [12] 0 0
Germany
State/province [12] 0 0
Aachen
Country [13] 0 0
Germany
State/province [13] 0 0
Berlin
Country [14] 0 0
Germany
State/province [14] 0 0
Cologne
Country [15] 0 0
Germany
State/province [15] 0 0
Frankfurt
Country [16] 0 0
Germany
State/province [16] 0 0
Ludwigshafen
Country [17] 0 0
Israel
State/province [17] 0 0
Beersheba
Country [18] 0 0
Israel
State/province [18] 0 0
Haifa
Country [19] 0 0
Israel
State/province [19] 0 0
Jerusalem
Country [20] 0 0
New Zealand
State/province [20] 0 0
Auckland
Country [21] 0 0
Norway
State/province [21] 0 0
Oslo
Country [22] 0 0
Singapore
State/province [22] 0 0
Singapore
Country [23] 0 0
South Africa
State/province [23] 0 0
Alberton
Country [24] 0 0
South Africa
State/province [24] 0 0
Cape Town
Country [25] 0 0
South Africa
State/province [25] 0 0
Centurion
Country [26] 0 0
South Africa
State/province [26] 0 0
Johannesburg
Country [27] 0 0
South Africa
State/province [27] 0 0
Soweto
Country [28] 0 0
Spain
State/province [28] 0 0
Madrid
Country [29] 0 0
Switzerland
State/province [29] 0 0
Lausanne
Country [30] 0 0
Switzerland
State/province [30] 0 0
Zurich
Country [31] 0 0
United Kingdom
State/province [31] 0 0
London
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Oxford

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

Ethics approval
Ethics application status

Summary
Brief summary
MP4OX is a novel oxygen therapeutic agent being developed as an ischemic rescue therapy to enhance perfusion and oxygenation of tissues at risk during hemorrhagic shock. MP4OX is a pegylated hemoglobin-based colloid. Due to its molecular size and unique oxygen dissociation characteristics, MP4OX targets delivery of oxygen to ischemic tissues. This study will evaluate the safety and efficacy of MP4OX treatment in trauma patients suffering from lactic acidosis due to severe hemorrhagic shock. The study hypothesis is that MP4OX will reverse the lactic acidosis by enhancing perfusion and oxygenation of ischemic tissues and thereby prevent and reduce the duration of organ failure and improve outcome in these patients.
Trial website
https://clinicaltrials.gov/study/NCT01262196
Trial related presentations / publications
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.
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.
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.
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.
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.
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.
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.
Olofsson CI, Gorecki AZ, Dirksen R, Kofranek I, Majewski JA, Mazurkiewicz T, Jahoda D, Fagrell B, Keipert PE, Hardiman YJ, Levy H; Study 6084 Clinical Investigators. Evaluation of MP4OX for prevention of perioperative hypotension in patients undergoing primary hip arthroplasty with spinal anesthesia: a randomized, double-blind, multicenter study. Anesthesiology. 2011 May;114(5):1048-63. doi: 10.1097/ALN.0b013e318215e198.
van der Linden P, Gazdzik TS, Jahoda D, Heylen RJ, Skowronski JC, Pellar D, Kofranek I, Gorecki AZ, Fagrell B, Keipert PE, Hardiman YJ, Levy H; 6090 Study Investigators. A double-blind, randomized, multicenter study of MP4OX for treatment of perioperative hypotension in patients undergoing primary hip arthroplasty under spinal anesthesia. Anesth Analg. 2011 Apr;112(4):759-73. doi: 10.1213/ANE.0b013e31820c7b5f. Epub 2011 Feb 11.
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/NCT01262196