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Shock, HemorrhagicPhase 2NCT01004198

Phase IIa Study of MP4OX in Traumatic Hemorrhagic Shock Patients

A Phase 2 study testing MP4OX and Ringers Lactate solution in people with Shock, Hemorrhagic and Shock, Traumatic, run by Sangart at 13 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

MP4OX is a novel oxygen therapeutic agent specifically developed to perfuse and oxygenate tissue at risk for ischemia and hypoxia. MP4OX is a pegylated hemoglobin-based colloid and and as a result of its molecular size and unique oxygen dissociation characteristics, targets oxygen delivery to ischemic tissues by… Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
MP4OX and Ringers Lactate solution
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
13 sitesin 4 countries
Study dates
Dec 2009to Jun 2010
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 (blood lactate level ≥ 5 mmol/L; equivalent to ≥ 45 mg/dL)
  • Informed consent obtained before any study-related activities

Who cannot join

  • Not expected to survive 24 hours after randomization
  • 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, or known AIS = 5 if GCS > 5; Immediate open intracranial operation; Abnormal physical exam indicative of severe CNS or spinal injury
  • Significant ongoing uncontrolled hemorrhage where control of bleeding is not expected within 2 hours of randomization
  • Cardiac arrest prior to dosing
  • Estimated time from injury to dosing > 4 hours
  • Estimated time from hospital admission to randomization > 2 hours
Show all 10Show fewer
  • Known or suspected pregnancy (confirmed by urine test)
  • Previous participation in this study
  • Professional or ancillary personnel involved with this study
  • Receipt of any investigational drug(s) within 30 days prior to study

Trial locations and contacts

13 sites in 4 countries.

13 sites in 4 countries

South Africa6 sites
  • Netcare Union Hospital

    Alberton

  • Charlotte Maxeke Johannesburg Hospital

    Johannesburg

  • Netcare Milpark Hospital

    Johannesburg

  • Netcare Unitas Hospital, Centurian

    Pretoria

  • Steve Biko Academic Hospital

    Pretoria

  • Chris Hani Baragwanath Hospital

    Soweto

Other trials in South Africa

France4 sites
  • Centre Hospitalier de Bicêtre

    Le Kremlin-Bicêtre

  • CHRU de Lille - Hôpital Claude Huriez

    Lille

  • Hôpital Dupuytren

    Limoges

  • Hôpital Pitié-Salpêtrière

    Paris

Other trials in France

Germany2 sites
  • Charité Campus Virchow Klinikum

    Berlin

  • Klinikum der Johann-Wolfgang-Goethe-Universität

    Frankfurt

Other trials in Germany

United Kingdom1 site
  • The Royal London Hospital

    London

Other trials in United Kingdom

About this study

Official title: A Multi-center, Randomized, Double-blind, Controlled Dose-finding Study to Evaluate the Safety and Efficacy of MP4OX Treatment Plus Standard of Care in Severely Injured Trauma Patients With Lactic Acidosis Due to Hemorrhagic Shock

MP4OX is a novel oxygen therapeutic agent specifically developed to perfuse and oxygenate tissue at risk for ischemia and hypoxia. MP4OX is a pegylated hemoglobin-based colloid and and as a result of its molecular size and unique oxygen dissociation characteristics, targets oxygen delivery to ischemic tissues by selectively off-loading oxygen in tissues predisposed to low oxygen tension. Sangart is currently evaluating MP4OX to reduce organ dysfunction and failure in trauma patients with lactic acidosis due to severe hemorrhagic shock.

Read the detailed description

Acute traumatic injury, including both blunt and penetrating injury, is often associated with severe bleeding which can lead to hemorrhagic shock. During shock, inadequate perfusion of critical organs can lead to local ischemia and tissue hypoxia (insufficient oxygenation), which can be detected by an increase in serum lactate levels. Despite optimal care, more than 10% of trauma victims who reach hospital alive will die, and many will suffer from organ failure. Death and significant, persistent morbidity are consequences of trauma, and traumatic injuries are associated with lost productivity, reduced quality of life, and direct costs to patients and health care systems worldwide. Current therapies, which also include blood transfusion, are aimed at supporting failing organs, but a therapeutic agent that could help to quickly restore adequate oxygenation may be beneficial to prevent or shorten duration of organ failure and improve patient outcome.

Direct support for the proposed clinical application to use MP4OX in resuscitation from hemorrhage is found in preclinical animal studies. Using a pig model of uncontrolled hemorrhage and resuscitation, survival was greater and restoration of hemodynamics and acid-base status were improved with MP4OX relative to an equivalent volume of crystalloid, pentastarch, or unmodified hemoglobin. Administration of MP4OX improved 24-hour survival, stabilized cardiac output and arterial pressure at nearly normal levels, and reduced lactate levels more effectively than the control fluids. Importantly, these benefits of MP4OX were observed with or without co-administration of autologous blood, suggesting that blood alone was not sufficient to achieve complete resuscitation, and that the effects of MP4OX appear to be additional to those of blood.

Being tested
MP4OX, Ringers Lactate solution
Keywords
Trauma, Hemorrhage, Hemorrhagic shock, Lactic acidosis, Oxygen carriers, Oxygen therapeutics, Hemoglobin solutions, Hemoglobin substitutes, Red cell substitutes, PEG-hemoglobin
Medical subject headings
Shock, Hemorrhagic, Shock, Traumatic, Acidosis, Lactic, Wounds and Injuries, Hemorrhage

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MP4OXDrug

    Also called MP4, MalPEG-Hb, PEG-Hb, Pegylated-Hb

    4.3 g/dL PEG-Hb solution in lactated electrolyte solution

  • MP4OXDrug

    Also called MP4, MalPEG-Hb, PEG-Hb, Pegylated-Hb

    4.3 g/dL PEG-Hb solution in lactated electrolyte solution

  • Ringers Lactate solutionDrug

    Also called Lactated Ringers, Hartmann's solution

    Ringers Lactate solution for Injection

Study groups in NCT01004198
Study groupRoleWhat they receive
MP4OX - 250Experimental250 mL dose
Receives: Drug: MP4OX
MP4OX - 500Experimental500 mL dose
Receives: Drug: MP4OX
Ringers Lactate solutionActive comparator500 mL dose
Receives: Drug: Ringers Lactate solution

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Serum lactate clearance

    Measured: 2 hours

Secondary outcomes (7)
  1. All-cause mortality

    Measured: 28 days

  2. Ventilator-free days

    Measured: 28 days

  3. ICU-free days

    Measured: 28 days

  4. Hospital-free days

    Measured: 28 days

  5. Sepsis-related Organ Failure Assessment (SOFA) score

    Measured: Daily

  6. Modified Denver score

    Measured: Daily

  7. Composite endpoint of Time to Complete Organ Failure Resolution (CTCOFR)

    Measured: At 14 and 21 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Oct 2009 (estimated)
  2. Study startDec 2009
  3. Primary completionJun 2010
  4. Study completionJun 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01004198
Sponsor's protocol ID
TRA-204
Status last verified
Aug 2013
First submitted
28 Oct 2009
Last updated
19 Aug 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • Olofsson C, Ahl T, Johansson T, Larsson S, Nellgard P, Ponzer S, Fagrell B, Przybelski R, Keipert P, Winslow N, Winslow RM. A multicenter clinical study of the safety and activity of maleimide-polyethylene glycol-modified Hemoglobin (Hemospan) in patients undergoing major orthopedic surgery. Anesthesiology. 2006 Dec;105(6):1153-63. doi: 10.1097/00000542-200612000-00015.

    PubMed 17122578
  • Olofsson C, Nygards EB, Ponzer S, Fagrell B, Przybelski R, Keipert PE, Winslow N, Winslow RM. A randomized, single-blind, increasing dose safety trial of an oxygen-carrying plasma expander (Hemospan) administered to orthopaedic surgery patients with spinal anaesthesia. Transfus Med. 2008 Feb;18(1):28-39. doi: 10.1111/j.1365-3148.2007.00811.x.

    PubMed 18279190
  • 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.

    PubMed 18948027
  • 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.

    PubMed 18212644
  • 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.

    PubMed 16096458
  • 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.

    PubMed 14729723
  • 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.

    PubMed 19178457
  • 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.

    PubMed 18837531
  • 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.

    PubMed 16857991
  • 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.

    PubMed 21317165

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MP4OX and Ringers Lactate solution in people with Shock, Hemorrhagic and Shock, Traumatic, run by Sangart at 13 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in South Africa, France, Germany, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Serum lactate clearance (time frame: 2 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01004198, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2013.

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