<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02187120</url>
  </required_header>
  <id_info>
    <org_study_id>APP1044894</org_study_id>
    <secondary_id>U1111-1160-6738</secondary_id>
    <nct_id>NCT02187120</nct_id>
  </id_info>
  <brief_title>Pre-hospital Anti-fibrinolytics for Traumatic Coagulopathy and Haemorrhage (The PATCH Study)</brief_title>
  <acronym>PATCH</acronym>
  <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.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Monash University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Health and Medical Research Council, Australia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Health Research Council, New Zealand</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Monash University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research is to determine whether giving severely injured adults a drug&#xD;
      called tranexamic acid (TXA) as soon as possible after injury will improve their chances of&#xD;
      survival and their level of recovery at six months.&#xD;
&#xD;
      After severe injury, a person may have uncontrolled bleeding that places them at high risk of&#xD;
      bleeding to death. Coagulation (the formation of blood clots) is an important process in the&#xD;
      body that helps to control blood loss. Up to a quarter of people that are severely injured&#xD;
      have a condition called acute traumatic coagulopathy. This condition affects coagulation and&#xD;
      results in the break down of blood clots (fibrinolysis) that can lead to increased blood loss&#xD;
      and an increased risk of dying.&#xD;
&#xD;
      TXA is an anti-fibrinolytic drug that might help to reduce the effects of acute traumatic&#xD;
      coagulopathy by preventing blood clots from breaking down and helping to control bleeding. In&#xD;
      Australia, TXA is approved for use by the Therapeutic Goods Administration (TGA) to reduce&#xD;
      blood loss or the need for blood transfusion in patients undergoing surgery (i.e. cardiac&#xD;
      surgery, knee or hip arthroplasty). Recent evidence from a large clinical trial (CRASH-2)&#xD;
      showed early treatment with TXA reduced the risk of death in severely injured patients,&#xD;
      however the majority of patients involved in the study were injured in countries where&#xD;
      prehospital care is limited and rapid access to lifesaving treatments is limited compared to&#xD;
      that available in countries like Australia and New Zealand. It is unclear whether TXA will&#xD;
      reduce the risk of death to the same degree when it is given alongside other lifesaving&#xD;
      treatments that are available to patients soon after injury in these countries.&#xD;
&#xD;
      The hypothesis is that TXA given early to injured patients who are at risk of acute traumatic&#xD;
      coagulopathy and who are treated in countries with systems providing advanced trauma care&#xD;
      reduces mortality and improves recovery at 6-months after injury.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 28, 2014</start_date>
  <completion_date type="Actual">September 7, 2022</completion_date>
  <primary_completion_date type="Actual">May 9, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>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).</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Units of blood products used (red blood cells, plasma, platelets, prothrombin complex concentrate, fibrinogen, Factor VIIa, cryoprecipitate)</measure>
    <time_frame>24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coagulation assessed using the international normalised ratio (INR)</measure>
    <time_frame>Immediately upon patient arrival to hospital</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coagulation assessed using the international normalised ratio (INR)</measure>
    <time_frame>At the end of 8 hour infusion of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coagulation assessed using the international normalised ratio (INR)</measure>
    <time_frame>24 hours after pre-hospital dose of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coagulation assessed by activated partial thromboplastin time (APTT)</measure>
    <time_frame>Immediately upon patient arrival to hospital</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coagulation assessed by activated partial thromboplastin time (APTT)</measure>
    <time_frame>At the end of 8 hour infusion of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coagulation assessed by activated partial thromboplastin time (APTT)</measure>
    <time_frame>24 hours after pre-hospital dose of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet count</measure>
    <time_frame>Immediately upon patient arrival to hospital</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet count</measure>
    <time_frame>At the end of 8 hour infusion of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet count</measure>
    <time_frame>24 hours after pre-hospital dose of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vascular occlusive events (myocardial infarction, stroke, deep venous thrombosis (DVT), pulmonary embolus (PE))</measure>
    <time_frame>Hospital discharge (or up to 28 days in hospital)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilator-free days</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury</measure>
    <time_frame>24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of sepsis</measure>
    <time_frame>Hospital discharge (or up to 28 days in hospital)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life measured using WHODAS 2.0</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life measured using the EuroQOL 5 dimensions questionnaire (EQ-5D)</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with serious adverse events</measure>
    <time_frame>hospital discharge (or up to 28 days in hospital)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coagulation assessed by fibrinogen</measure>
    <time_frame>Immediately upon patient arrival to hospital</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coagulation assessed by fibrinogen</measure>
    <time_frame>At the end of 8 hour infusion of study drug</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coagulation assessed by fibrinogen</measure>
    <time_frame>24 hours after pre-hospital dose of study drug</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Blood lactate concentration</measure>
    <time_frame>Immediately upon patient arrival to hospital</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of fibrinolytic activity</measure>
    <time_frame>At the end of 8 hour infusion of study drug</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of fibrinolytic activity</measure>
    <time_frame>24 hours after first (prehospital) dose of study drug</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of plasmin/anti-plasmin complexes</measure>
    <time_frame>At the end of 8 hour infusion of study drug</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of plasmin/anti-plasmin complexes</measure>
    <time_frame>24 hours after first (pre-hospital) dose of study drug</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of tissue type plasminogen activator (tPA)</measure>
    <time_frame>At the end of 8 hour infusion of study drug</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of tissue type plasminogen activator (tPA)</measure>
    <time_frame>24 hours after first (pre-hospital) dose of study drug</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of plasminogen activator inhibitor 1 (PAI-1)</measure>
    <time_frame>At the end of 8 hour infusion of study drug</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of plasminogen activator inhibitor 1 (PAI-1)</measure>
    <time_frame>24 hours after first (pre-hospital) dose of study drug</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of t-PA/PAI-1 complexes</measure>
    <time_frame>At the end of 8 hour infusion of study drug</time_frame>
    <description>Substudy</description>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of t-PA/PAI-1 complexes</measure>
    <time_frame>24 hours after first (pre-hospital) dose of study drug</time_frame>
    <description>Substudy</description>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of thrombin activatable fibrinolysis inhibitor (TAFI)</measure>
    <time_frame>At the end of 8 hour infusion of study drug</time_frame>
    <description>Substudy</description>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of thrombin activatable fibrinolysis inhibitor (TAFI)</measure>
    <time_frame>24 hours after first (pre-hospital) dose of study drug</time_frame>
    <description>Substudy</description>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of interleukins (IL-2, IL-4, IL-6, IL-8, IL-10)</measure>
    <time_frame>At the end of 8 hour infusion of study drug</time_frame>
    <description>Substudy</description>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of interleukins (IL-2, IL-4, IL-6, IL-8, IL-10)</measure>
    <time_frame>24 hours after first (pre-hospital) dose of study drug</time_frame>
    <description>Substudy</description>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of granulocyte macrophage colony-stimulating factor (GM-CSF)</measure>
    <time_frame>At the end of 8 hour infusion of study drug</time_frame>
    <description>Substudy</description>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of granulocyte macrophage colony-stimulating factor (GM-CSF)</measure>
    <time_frame>24 hours after first (pre-hospital) dose of study drug</time_frame>
    <description>Substudy</description>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of interferon gamma</measure>
    <time_frame>At the end of 8 hour infusion of study drug</time_frame>
    <description>Substudy</description>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of interferon gamma</measure>
    <time_frame>24 hours after first (pre-hospital) dose of study drug</time_frame>
    <description>Substudy</description>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of tumour necrosis factor alpha</measure>
    <time_frame>At the end of 8 hour infusion of study drug</time_frame>
    <description>Substudy</description>
  </other_outcome>
  <other_outcome>
    <measure>Laboratory analysis of tumour necrosis factor alpha</measure>
    <time_frame>24 hours after first (pre-hospital) dose of study drug</time_frame>
    <description>Substudy</description>
  </other_outcome>
  <other_outcome>
    <measure>TXA concentration in blood</measure>
    <time_frame>8 hours after first dose of study drug</time_frame>
    <description>substudy</description>
  </other_outcome>
  <other_outcome>
    <measure>TXA concentration in blood</measure>
    <time_frame>24 hours after first dose of study drug</time_frame>
    <description>substudy</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1310</enrollment>
  <condition>Wounds and Injuries</condition>
  <condition>Acute Coagulopathy</condition>
  <arm_group>
    <arm_group_label>Tranexamic Acid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.&#xD;
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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>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).&#xD;
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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tranexamic Acid</intervention_name>
    <description>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.</description>
    <arm_group_label>Tranexamic Acid</arm_group_label>
    <other_name>Cyklokapron</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients (estimated age 18 years or older)&#xD;
&#xD;
          -  Injured through any mechanism&#xD;
&#xD;
          -  Coagulopathy of severe trauma (COAST) score of 3 points or greater&#xD;
&#xD;
          -  First dose of study drug can be administered within three hours of injury&#xD;
&#xD;
          -  Patients to be transported to a participating trauma centre&#xD;
&#xD;
        COAST score&#xD;
&#xD;
          -  Entrapment (ie in vehicle) [Yes = 1, No = 0]&#xD;
&#xD;
          -  Systolic blood pressure [&lt;90 mmHg = 2, &lt;100 mmHg = 1, ≥100 mmHg = 0]&#xD;
&#xD;
          -  Temperature [&lt;32℃ =2, &lt;35℃ = 1, ≥35℃ = 0]&#xD;
&#xD;
          -  Major chest injury likely to require intervention (e.g. decompression, chest tube)&#xD;
             [Yes = 1, No = 0]&#xD;
&#xD;
          -  Likely intra-abdominal or pelvic injury [Yes = 1, No = 0]&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Suspected pregnancy&#xD;
&#xD;
          -  Nursing home residents&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Russell L Gruen, MBBS PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Monash University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Lismore Base Hospital</name>
      <address>
        <city>Lismore</city>
        <state>New South Wales</state>
        <zip>2480</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NNSW Medical Retrieval Service</name>
      <address>
        <city>Lismore</city>
        <state>New South Wales</state>
        <zip>2480</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Hunter Hospital</name>
      <address>
        <city>Newcastle</city>
        <state>New South Wales</state>
        <zip>2305</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CareFlight</name>
      <address>
        <city>Northmead</city>
        <state>New South Wales</state>
        <zip>2152</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Orange Base Hospital</name>
      <address>
        <city>Orange</city>
        <state>New South Wales</state>
        <zip>2800</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ambulance Service of New South Wales</name>
      <address>
        <city>Rozelle</city>
        <state>New South Wales</state>
        <zip>2039</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal North Shore Hospital</name>
      <address>
        <city>St Leonards</city>
        <state>New South Wales</state>
        <zip>2065</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Liverpool Hospital</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2170</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wagga Wagga Base Hospital</name>
      <address>
        <city>Wagga Wagga</city>
        <state>New South Wales</state>
        <zip>2650</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Westmead Hospital</name>
      <address>
        <city>Westmead</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St John Ambulance</name>
      <address>
        <city>Darwin</city>
        <state>Northern Territory</state>
        <zip>0810</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Darwin Hospital</name>
      <address>
        <city>Darwin</city>
        <state>Northern Territory</state>
        <zip>0811</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Brisbane and Women's Hospital</name>
      <address>
        <city>Brisbane</city>
        <state>Queensland</state>
        <zip>4006</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Alexandra Hospital</name>
      <address>
        <city>Brisbane</city>
        <state>Queensland</state>
        <zip>4102</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gold Coast Hospital</name>
      <address>
        <city>Gold Coast</city>
        <state>Queensland</state>
        <zip>4215</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queensland Ambulance Service</name>
      <address>
        <city>Kedron</city>
        <state>Queensland</state>
        <zip>4031</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Adelaide Hospital</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Flinders Medical Centre</name>
      <address>
        <city>Bedford Park</city>
        <state>South Australia</state>
        <zip>5042</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Australia Ambulance Service</name>
      <address>
        <city>Eastwood</city>
        <state>South Australia</state>
        <zip>5063</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ambulance Tasmania</name>
      <address>
        <city>Hobart</city>
        <state>Tasmania</state>
        <zip>7000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Hobart Hospital</name>
      <address>
        <city>Hobart</city>
        <state>Tasmania</state>
        <zip>7000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ambulance Victoria</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>2000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Alfred Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3004</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Melbourne Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St John Ambulance Western Australia</name>
      <address>
        <city>Geraldton</city>
        <state>Western Australia</state>
        <zip>6530</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Perth Hospital</name>
      <address>
        <city>Perth</city>
        <state>Western Australia</state>
        <zip>6000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St John Ambulance</name>
      <address>
        <city>Albany</city>
        <zip>0632</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Auckland City Hospital</name>
      <address>
        <city>Auckland</city>
        <zip>1142</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Middlemore Hospital</name>
      <address>
        <city>Auckland</city>
        <zip>2025</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Waikato Hospital</name>
      <address>
        <city>Hamilton West</city>
        <zip>3204</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hawke's Bay</name>
      <address>
        <city>Hastings</city>
        <zip>4156</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wellington Free Ambulance</name>
      <address>
        <city>Wellington</city>
        <zip>6011</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wellington Hospital</name>
      <address>
        <city>Wellington</city>
        <zip>6021</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>New Zealand</country>
  </location_countries>
  <reference>
    <citation>Gruen RL, Jacobs IG, Reade MC; PATCH-Trauma study. Trauma and tranexamic acid. Med J Aust. 2013 Sep 2;199(5):310-1. doi: 10.5694/mja13.10747. No abstract available.</citation>
    <PMID>23992173</PMID>
  </reference>
  <reference>
    <citation>Reade MC, Pitt V, Gruen RL. Tranexamic acid and trauma: current status and knowledge gaps with recommended research priorities. Shock. 2013 Aug;40(2):160-1. doi: 10.1097/SHK.0b013e31829ab240. No abstract available.</citation>
    <PMID>23860584</PMID>
  </reference>
  <reference>
    <citation>Mitra B, Mazur S, Cameron PA, Bernard S, Burns B, Smith A, Rashford S, Fitzgerald M, Smith K, Gruen RL; PATCH-Trauma Study Investigators. Tranexamic acid for trauma: filling the 'GAP' in evidence. Emerg Med Australas. 2014 Apr;26(2):194-7. doi: 10.1111/1742-6723.12172.</citation>
    <PMID>24708011</PMID>
  </reference>
  <reference>
    <citation>Gruen RL, Mitra B. Tranexamic acid for trauma. Lancet. 2011 Mar 26;377(9771):1052-4. doi: 10.1016/S0140-6736(11)60396-6. No abstract available.</citation>
    <PMID>21439636</PMID>
  </reference>
  <reference>
    <citation>Mitra B, Cameron PA, Mori A, Maini A, Fitzgerald M, Paul E, Street A. Early prediction of acute traumatic coagulopathy. Resuscitation. 2011 Sep;82(9):1208-13. doi: 10.1016/j.resuscitation.2011.04.007. Epub 2011 Apr 21.</citation>
    <PMID>21600687</PMID>
  </reference>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 8, 2014</study_first_submitted>
  <study_first_submitted_qc>July 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 10, 2014</study_first_posted>
  <last_update_submitted>January 26, 2023</last_update_submitted>
  <last_update_submitted_qc>January 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Monash University</investigator_affiliation>
    <investigator_full_name>Russell Gruen</investigator_full_name>
    <investigator_title>Professor of Surgery and Public Health</investigator_title>
  </responsible_party>
  <keyword>Wounds and Injuries</keyword>
  <keyword>Acute Coagulopathy</keyword>
  <keyword>Tranexamic Acid</keyword>
  <keyword>Emergency Medical Services</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemostatic Disorders</mesh_term>
    <mesh_term>Blood Coagulation Disorders</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tranexamic Acid</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02187120
org study id: APP1044894
secondary id: U1111-1160-6738
nct id: NCT02187120
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: 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
measure: Units of blood products used (red blood cells, plasma, platelets, prothrombin complex concentrate, fibrinogen, Factor VIIa, cryoprecipitate)
time frame: 24 hours
measure: Coagulation assessed using the international normalised ratio (INR)
time frame: Immediately upon patient arrival to hospital
measure: Coagulation assessed using the international normalised ratio (INR)
time frame: At the end of 8 hour infusion of study drug
measure: Coagulation assessed using the international normalised ratio (INR)
time frame: 24 hours after pre-hospital dose of study drug
measure: Coagulation assessed by activated partial thromboplastin time (APTT)
time frame: Immediately upon patient arrival to hospital
measure: Coagulation assessed by activated partial thromboplastin time (APTT)
time frame: At the end of 8 hour infusion of study drug
measure: Coagulation assessed by activated partial thromboplastin time (APTT)
time frame: 24 hours after pre-hospital dose of study drug
measure: Platelet count
time frame: Immediately upon patient arrival to hospital
measure: Platelet count
time frame: At the end of 8 hour infusion of study drug
measure: Platelet count
time frame: 24 hours after pre-hospital dose of study drug
measure: Vascular occlusive events (myocardial infarction, stroke, deep venous thrombosis (DVT), pulmonary embolus (PE))
time frame: Hospital discharge (or up to 28 days in hospital)
measure: Ventilator-free days
time frame: 28 days
measure: Mortality
time frame: 24 hours
measure: Mortality
time frame: 28 days
measure: Mortality
time frame: 6 months
measure: Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury
time frame: 24 hours
measure: Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury
time frame: 28 days
measure: Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury
time frame: 6 months
measure: Cumulative incidence of sepsis
time frame: Hospital discharge (or up to 28 days in hospital)
measure: Quality of life measured using WHODAS 2.0
time frame: 6 months
measure: Quality of life measured using the EuroQOL 5 dimensions questionnaire (EQ-5D)
time frame: 6 months
measure: Number of participants with serious adverse events
time frame: hospital discharge (or up to 28 days in hospital)
measure: Coagulation assessed by fibrinogen
time frame: Immediately upon patient arrival to hospital
measure: Coagulation assessed by fibrinogen
time frame: At the end of 8 hour infusion of study drug
measure: Coagulation assessed by fibrinogen
time frame: 24 hours after pre-hospital dose of study drug
measure: Blood lactate concentration
time frame: Immediately upon patient arrival to hospital
measure: Laboratory analysis of fibrinolytic activity
time frame: At the end of 8 hour infusion of study drug
measure: Laboratory analysis of fibrinolytic activity
time frame: 24 hours after first (prehospital) dose of study drug
measure: Laboratory analysis of plasmin/anti-plasmin complexes
time frame: At the end of 8 hour infusion of study drug
measure: Laboratory analysis of plasmin/anti-plasmin complexes
time frame: 24 hours after first (pre-hospital) dose of study drug
measure: Laboratory analysis of tissue type plasminogen activator (tPA)
time frame: At the end of 8 hour infusion of study drug
measure: Laboratory analysis of tissue type plasminogen activator (tPA)
time frame: 24 hours after first (pre-hospital) dose of study drug
measure: Laboratory analysis of plasminogen activator inhibitor 1 (PAI-1)
time frame: At the end of 8 hour infusion of study drug
measure: Laboratory analysis of plasminogen activator inhibitor 1 (PAI-1)
time frame: 24 hours after first (pre-hospital) dose of study drug
measure: Laboratory analysis of t-PA/PAI-1 complexes
time frame: At the end of 8 hour infusion of study drug
description: Substudy
measure: Laboratory analysis of t-PA/PAI-1 complexes
time frame: 24 hours after first (pre-hospital) dose of study drug
description: Substudy
measure: Laboratory analysis of thrombin activatable fibrinolysis inhibitor (TAFI)
time frame: At the end of 8 hour infusion of study drug
description: Substudy
measure: Laboratory analysis of thrombin activatable fibrinolysis inhibitor (TAFI)
time frame: 24 hours after first (pre-hospital) dose of study drug
description: Substudy
measure: 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
description: Substudy
measure: 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
description: Substudy
measure: Laboratory analysis of granulocyte macrophage colony-stimulating factor (GM-CSF)
time frame: At the end of 8 hour infusion of study drug
description: Substudy
measure: Laboratory analysis of granulocyte macrophage colony-stimulating factor (GM-CSF)
time frame: 24 hours after first (pre-hospital) dose of study drug
description: Substudy
measure: Laboratory analysis of interferon gamma
time frame: At the end of 8 hour infusion of study drug
description: Substudy
measure: Laboratory analysis of interferon gamma
time frame: 24 hours after first (pre-hospital) dose of study drug
description: Substudy
measure: Laboratory analysis of tumour necrosis factor alpha
time frame: At the end of 8 hour infusion of study drug
description: Substudy
measure: Laboratory analysis of tumour necrosis factor alpha
time frame: 24 hours after first (pre-hospital) dose of study drug
description: Substudy
measure: TXA concentration in blood
time frame: 8 hours after first dose of study drug
description: substudy
measure: TXA concentration in blood
time frame: 24 hours after first dose of study drug
description: substudy
arm group label: Tranexamic Acid
arm group type: Experimental
description: 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.
arm group label: Placebo
arm group type: Placebo Comparator
description: 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.
intervention type: Drug
intervention name: Tranexamic Acid
description: 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.
arm group label: Tranexamic Acid
other name: Cyklokapron
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Russell L Gruen, MBBS PhD
role: Principal Investigator
affiliation: Monash University
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country: Australia
country: New Zealand
citation: Gruen RL, Jacobs IG, Reade MC; PATCH-Trauma study. Trauma and tranexamic acid. Med J Aust. 2013 Sep 2;199(5):310-1. doi: 10.5694/mja13.10747. No abstract available.
PMID: 23992173
citation: Reade MC, Pitt V, Gruen RL. Tranexamic acid and trauma: current status and knowledge gaps with recommended research priorities. Shock. 2013 Aug;40(2):160-1. doi: 10.1097/SHK.0b013e31829ab240. No abstract available.
PMID: 23860584
citation: Mitra B, Mazur S, Cameron PA, Bernard S, Burns B, Smith A, Rashford S, Fitzgerald M, Smith K, Gruen RL; PATCH-Trauma Study Investigators. Tranexamic acid for trauma: filling the 'GAP' in evidence. Emerg Med Australas. 2014 Apr;26(2):194-7. doi: 10.1111/1742-6723.12172.
PMID: 24708011
citation: Gruen RL, Mitra B. Tranexamic acid for trauma. Lancet. 2011 Mar 26;377(9771):1052-4. doi: 10.1016/S0140-6736(11)60396-6. No abstract available.
PMID: 21439636
citation: Mitra B, Cameron PA, Mori A, Maini A, Fitzgerald M, Paul E, Street A. Early prediction of acute traumatic coagulopathy. Resuscitation. 2011 Sep;82(9):1208-13. doi: 10.1016/j.resuscitation.2011.04.007. Epub 2011 Apr 21.
PMID: 21600687
responsible party type: Principal Investigator
investigator affiliation: Monash University
investigator full name: Russell Gruen
investigator title: Professor of Surgery and Public Health
mesh term: Hemostatic Disorders
mesh term: Blood Coagulation Disorders
mesh term: Wounds and Injuries
mesh term: Tranexamic Acid