Pre-hospital Anti-fibrinolytics for Traumatic Coagulopathy and Haemorrhage (The PATCH Study)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by National Trauma Research Institute
Sponsor:
Collaborator:
National Health and Medical Research Council, Australia
Information provided by (Responsible Party):
Russell Gruen, National Trauma Research Institute
ClinicalTrials.gov Identifier:
NCT02187120
First received: July 8, 2014
Last updated: August 20, 2014
Last verified: August 2014
  Purpose

The purpose of this research is to determine whether giving severely injured adults a drug called tranexamic acid (TXA) as soon as possible after injury will improve their chances of survival and their level of recovery at six months.

After severe injury, a person may have uncontrolled bleeding that places them at high risk of bleeding to death. Coagulation (the formation of blood clots) is an important process in the body that helps to control blood loss. Up to a quarter of people that are severely injured have a condition called acute traumatic coagulopathy. This condition affects coagulation and results in the break down of blood clots (fibrinolysis) that can lead to increased blood loss and an increased risk of dying.

TXA is an anti-fibrinolytic drug that might help to reduce the effects of acute traumatic coagulopathy by preventing blood clots from breaking down and helping to control bleeding. In Australia, TXA is approved for use by the Therapeutic Goods Administration (TGA) to reduce blood loss or the need for blood transfusion in patients undergoing surgery (i.e. cardiac surgery, knee or hip arthroplasty). Recent evidence from a large clinical trial (CRASH-2) showed early treatment with TXA reduced the risk of death in severely injured patients, however the majority of patients involved in the study were injured in countries where prehospital care is limited and rapid access to lifesaving treatments is limited compared to that available in countries like Australia and New Zealand. It is unclear whether TXA will reduce the risk of death to the same degree when it is given alongside other lifesaving treatments that are available to patients soon after injury in these countries.

The hypothesis is that TXA given early to injured patients who are at risk of acute traumatic coagulopathy and who are treated in countries with systems providing advanced trauma care reduces mortality and improves recovery at 6-months after injury.


Condition Intervention Phase
Wounds and Injuries
Acute Coagulopathy
Drug: Tranexamic Acid
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-centre Randomised, Double-blinded, Placebo-controlled Trial of Pre-hospital Treatment With Tranexamic Acid for Severely Injured Patients at Risk of Acute Traumatic Coagulopathy.

Resource links provided by NLM:


Further study details as provided by National Trauma Research Institute:

Primary Outcome Measures:
  • The proportion of patients with a favourable outcome (moderate disability or good recovery, GOSE scores 5-8) compared to those who have died (GOSE 1), or have severe disability (GOSE 2-4). [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Units of blood products used (red blood cells, plasma, platelets, prothrombin complex concentrate, fibrinogen, Factor VIIa, cryoprecipitate) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Coagulation assessed using the international normalised ratio (INR) [ Time Frame: On patient arrival to hospital ] [ Designated as safety issue: No ]
  • Coagulation assessed using the international normalised ratio (INR) [ Time Frame: At the end of 8 hour infusion of study drug ] [ Designated as safety issue: No ]
  • Coagulation assessed using the international normalised ratio (INR) [ Time Frame: 24 hours after pre-hospital dose of study drug ] [ Designated as safety issue: No ]
  • Coagulation assessed by activated partial thromboplastin time (APTT) [ Time Frame: On patient arrival to hospital ] [ Designated as safety issue: No ]
  • Coagulation assessed by activated partial thromboplastin time (APTT) [ Time Frame: At the end of 8 hour infusion of study drug ] [ Designated as safety issue: No ]
  • Coagulation assessed by activated partial thromboplastin time (APTT) [ Time Frame: 24 hours after pre-hospital dose of study drug ] [ Designated as safety issue: No ]
  • Platelet count [ Time Frame: On patient arrival to hospital ] [ Designated as safety issue: No ]
  • Platelet count [ Time Frame: At the end of 8 hour infusion of study drug ] [ Designated as safety issue: No ]
  • Platelet count [ Time Frame: 24 hours after pre-hospital dose of study drug ] [ Designated as safety issue: No ]
  • Vascular occlusive events (myocardial infarction, stroke, deep venous thrombosis (DVT), pulmonary embolus (PE)) [ Time Frame: Hospital discharge (or up to 28 days in hospital) ] [ Designated as safety issue: Yes ]
  • Ventilator-free days [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Mortality [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Mortality [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Mortality [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Cumulative incidence of sepsis [ Time Frame: Hospital discharge (or up to 28 days in hospital) ] [ Designated as safety issue: No ]
  • Pain measured using the modified Brief Pain Inventory (mBPI) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Quality of life measured using the 12-item short form health survey (SF12®) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Quality of life measured using the EuroQOL 5 dimensions questionnaire (EQ-5D) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Number of participants with serious adverse events [ Time Frame: hospital discharge (or up to 28 days in hospital) ] [ Designated as safety issue: Yes ]
  • Coagulation assessed by fibrinogen [ Time Frame: On patient arrival to hospital ] [ Designated as safety issue: No ]
  • Coagulation assessed by fibrinogen [ Time Frame: At the end of 8 hour infusion of study drug ] [ Designated as safety issue: No ]
  • Coagulation assessed by fibrinogen [ Time Frame: 24 hours after pre-hospital dose of study drug ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Blood lactate concentration [ Time Frame: On patient arrival to hospital ] [ Designated as safety issue: No ]
  • Laboratory analysis of fibrinolytic activity [ Time Frame: At the end of 8 hour infusion of study drug ] [ Designated as safety issue: No ]
  • Laboratory analysis of fibrinolytic activity [ Time Frame: 24 hours after first (prehospital) dose of study drug ] [ Designated as safety issue: No ]
  • Laboratory analysis of plasmin/anti-plasmin complexes [ Time Frame: At the end of 8 hour infusion of study drug ] [ Designated as safety issue: No ]
  • Laboratory analysis of plasmin/anti-plasmin complexes [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ] [ Designated as safety issue: No ]
  • Laboratory analysis of tissue type plasminogen activator (tPA) [ Time Frame: At the end of 8 hour infusion of study drug ] [ Designated as safety issue: No ]
  • Laboratory analysis of tissue type plasminogen activator (tPA) [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ] [ Designated as safety issue: No ]
  • Laboratory analysis of plasminogen activator inhibitor 1 (PAI-1) [ Time Frame: At the end of 8 hour infusion of study drug ] [ Designated as safety issue: No ]
  • Laboratory analysis of plasminogen activator inhibitor 1 (PAI-1) [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ] [ Designated as safety issue: No ]
  • Laboratory analysis of t-PA/PAI-1 complexes [ Time Frame: At the end of 8 hour infusion of study drug ] [ Designated as safety issue: No ]
    Substudy

  • Laboratory analysis of t-PA/PAI-1 complexes [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ] [ Designated as safety issue: No ]
    Substudy

  • Laboratory analysis of thrombin activatable fibrinolysis inhibitor (TAFI) [ Time Frame: At the end of 8 hour infusion of study drug ] [ Designated as safety issue: No ]
    Substudy

  • Laboratory analysis of thrombin activatable fibrinolysis inhibitor (TAFI) [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ] [ Designated as safety issue: No ]
    Substudy

  • Laboratory analysis of interleukins (IL-2, IL-4, IL-6, IL-8, IL-10) [ Time Frame: At the end of 8 hour infusion of study drug ] [ Designated as safety issue: No ]
    Substudy

  • Laboratory analysis of interleukins (IL-2, IL-4, IL-6, IL-8, IL-10) [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ] [ Designated as safety issue: No ]
    Substudy

  • Laboratory analysis of granulocyte macrophage colony-stimulating factor (GM-CSF) [ Time Frame: At the end of 8 hour infusion of study drug ] [ Designated as safety issue: No ]
    Substudy

  • Laboratory analysis of granulocyte macrophage colony-stimulating factor (GM-CSF) [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ] [ Designated as safety issue: No ]
    Substudy

  • Laboratory analysis of interferon gamma [ Time Frame: At the end of 8 hour infusion of study drug ] [ Designated as safety issue: No ]
    Substudy

  • Laboratory analysis of interferon gamma [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ] [ Designated as safety issue: No ]
    Substudy

  • Laboratory analysis of tumour necrosis factor alpha [ Time Frame: At the end of 8 hour infusion of study drug ] [ Designated as safety issue: No ]
    Substudy

  • Laboratory analysis of tumour necrosis factor alpha [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ] [ Designated as safety issue: No ]
    Substudy

  • TXA concentration in blood [ Time Frame: 8 hours after first dose of study drug ] [ Designated as safety issue: No ]
    substudy

  • TXA concentration in blood [ Time Frame: 24 hours after first dose of study drug ] [ Designated as safety issue: No ]
    substudy


Estimated Enrollment: 1184
Study Start Date: July 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tranexamic Acid

As soon as possible after injury, emergency medical services clinicians will administer 1g Tranexamic Acid (10ml ampoule containing 100mg/ml Tranexamic Acid in water for injection) delivered intravenously using a slow push of the syringe.

As soon as possible after the patient arrives at hospital, clinicians will administer 1g Tranexamic acid (10ml ampoule containing 100mg/ml Tranexamic Acid in water for injection) added to up to one litre 0.9%w/v Sodium Chloride and the entire volume infused intravenously over 8 hours.

Drug: Tranexamic Acid
Tranexamic acid is a synthetic lysine derivative that inhibits fibrinolysis by blocking the lysine binding sites on plasminogen therefore inhibiting the conversion of plasminogen to plasmin. Intravenous injection of 1g Tranexamic Acid will be administered in the pre-hospital setting followed by 1g Tranexamic Acid infused intravenously over 8 hours initiated in the hospital emergency department.
Other Name: Cyklokapron
Placebo Comparator: Placebo

As soon as possible after injury, emergency medical services clinicians will administer a 10ml ampoule containing 0.9%w/v Sodium Chloride via intravenous injection using a slow push of the syringe (ampoules containing Sodium Chloride appear identical to the ampoules containing Tranexamic Acid).

As soon as possible after the patient arrives at hospital, clinicians will administer a second 10 ml ampoule containing 0.9%w/v Sodium Chloride added to up to one litre 0.9%w/v Sodium Chloride and the entire volume infused intravenously over 8 hours.

Drug: Placebo

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients (estimated age 18 years or older)
  • Injured through any mechanism
  • Coagulopathy of severe trauma (COAST) score of 3 points or greater
  • First dose of study drug can be administered within three hours of injury
  • Patients to be transported to a participating trauma centre

COAST score

  • Entrapment (ie in vehicle) [Yes = 1, No = 0]
  • Systolic blood pressure [<90 mmHg = 2, <100 mmHg = 1, ≥100 mmHg = 0]
  • Temperature [<32℃ =2, <35℃ = 1, ≥35℃ = 0]
  • Major chest injury likely to require intervention (e.g. decompression, chest tube) [Yes = 1, No = 0]
  • Likely intra-abdominal or pelvic injury [Yes = 1, No = 0]

Exclusion Criteria:

  • Suspected pregnancy
  • Nursing home residents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02187120

Contacts
Contact: Veronica Pitt, PhD 90768584 ext +613 veronica.pitt@monash.edu

Locations
Australia, New South Wales
John Hunter Hospital Not yet recruiting
Newcastle, New South Wales, Australia, 2305
Orange Base Hospital Not yet recruiting
Orange, New South Wales, Australia, 2800
Ambulance Service of New South Wales Not yet recruiting
Rozelle, New South Wales, Australia, 2039
Royal North Shore Hospital Not yet recruiting
St Leonards, New South Wales, Australia, 2065
Wagga Wagga Base Hospital Not yet recruiting
Wagga Wagga, New South Wales, Australia, 2650
Westmead Hospital Not yet recruiting
Westmead, New South Wales, Australia, 2145
Australia, Queensland
Princess Alexandra Hospital Not yet recruiting
Brisbane, Queensland, Australia, 4102
Royal Brisbane and Women's Hospital Not yet recruiting
Brisbane, Queensland, Australia, 4006
Gold Coast Hospital Not yet recruiting
Gold Coast, Queensland, Australia, 4215
Queensland Ambulance Service Not yet recruiting
Kedron, Queensland, Australia, 4031
Australia, South Australia
Royal Adelaide Hospital Not yet recruiting
Adelaide, South Australia, Australia, 5000
Flinders Medical Centre Not yet recruiting
Bedford Park, South Australia, Australia, 5042
South Australia Ambulance Service Not yet recruiting
Eastwood, South Australia, Australia, 5063
Australia, Tasmania
Royal Hobart Hospital Not yet recruiting
Hobart, Tasmania, Australia, 7000
Ambulance Tasmania Not yet recruiting
Hobart, Tasmania, Australia, 7000
Australia, Victoria
Ambulance Victoria Not yet recruiting
Melbourne, Victoria, Australia, 2000
Contact: Karen Smith, PhD    98403752 ext +613    karen.smith@ambulance.vic.gov.au   
Contact: Anthony De Wit    99459919 ext +613    anthony.dewit@ambulance.vic.gov.au   
Principal Investigator: Karen Smith, PhD         
Sub-Investigator: Anthony De Wit         
Royal Melbourne Hospital Not yet recruiting
Melbourne, Victoria, Australia, 3050
Contact: Rodney Judson, MBBS    93427323 ext +613    rodney.judson@mh.org.au   
Contact: Jonathon Knott, MBBS PhD    93427543 ext +613    jonathan.knott@mh.org.au   
Principal Investigator: Rodney Judson, MBBS         
Sub-Investigator: Jonathan Knott, MBBS PhD         
The Alfred Hospital Recruiting
Melbourne, Victoria, Australia, 3004
Contact: Russell L Gruen, MBBS PhD    90762561 ext +613    r.gruen@alfred.org.au   
Contact: Biswadev Mitra, MBBS PhD    90762782 ext +613    biswadev.mitra@monash.edu   
Principal Investigator: Russell L Gruen, MBBS PhD         
Sub-Investigator: Biswadev Mitra, MBBS PhD         
Sub-Investigator: Stephen Bernard, MBBS MD         
Sub-Investigator: Mark Fitzgerald, MBBS         
Sub-Investigator: Paul Myles, MBChB MD         
Sub-Investigator: Jamie Cooper, BMBS MD         
Sub-Investigator: Huyen Tran, MBBS(Hons)         
Australia, Western Australia
St John Ambulance Western Australia Not yet recruiting
Geraldton, Western Australia, Australia, 6530
Royal Perth Hospital Not yet recruiting
Perth, Western Australia, Australia, 6000
New Zealand
St John Ambulance Not yet recruiting
Albany, New Zealand, 0632
Auckland City Hospital Not yet recruiting
Auckland, New Zealand, 1142
Waikato Hospital Not yet recruiting
Hamilton West, New Zealand, 3204
Wellington Free Ambulance Not yet recruiting
Wellington, New Zealand, 6011
Wellington Hospital Not yet recruiting
Wellington, New Zealand, 6021
Sponsors and Collaborators
National Trauma Research Institute
National Health and Medical Research Council, Australia
Investigators
Principal Investigator: Russell L Gruen, MBBS PhD National Trauma Research Institute
  More Information

Additional Information:
Publications:
Responsible Party: Russell Gruen, Director, National Trauma Research Institute
ClinicalTrials.gov Identifier: NCT02187120     History of Changes
Other Study ID Numbers: APP1044894, U1111-1160-6738
Study First Received: July 8, 2014
Last Updated: August 20, 2014
Health Authority: Australia: Human Research Ethics Committee
Australia: National Health and Medical Research Council
Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by National Trauma Research Institute:
Wounds and Injuries
Acute Coagulopathy
Tranexamic Acid
Emergency Medical Services

Additional relevant MeSH terms:
Blood Coagulation Disorders
Hemostatic Disorders
Wounds and Injuries
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Vascular Diseases
Tranexamic Acid
Antifibrinolytic Agents
Coagulants
Fibrin Modulating Agents
Hematologic Agents
Hemostatics
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014