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

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ClinicalTrials.gov Identifier: NCT02187120
Recruitment Status : Recruiting
First Posted : July 10, 2014
Last Update Posted : August 6, 2018
Sponsor:
Collaborators:
National Health and Medical Research Council, Australia
Health Research Council, New Zealand
Information provided by (Responsible Party):
Russell Gruen, Monash University

Tracking Information
First Submitted Date  ICMJE July 8, 2014
First Posted Date  ICMJE July 10, 2014
Last Update Posted Date August 6, 2018
Actual Study Start Date  ICMJE July 2014
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 9, 2014)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02187120 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 6, 2016)
  • Units of blood products used (red blood cells, plasma, platelets, prothrombin complex concentrate, fibrinogen, Factor VIIa, cryoprecipitate) [ Time Frame: 24 hours ]
  • Coagulation assessed using the international normalised ratio (INR) [ Time Frame: Immediately upon patient arrival to hospital ]
  • Coagulation assessed using the international normalised ratio (INR) [ Time Frame: At the end of 8 hour infusion of study drug ]
  • Coagulation assessed using the international normalised ratio (INR) [ Time Frame: 24 hours after pre-hospital dose of study drug ]
  • Coagulation assessed by activated partial thromboplastin time (APTT) [ Time Frame: Immediately upon patient arrival to hospital ]
  • Coagulation assessed by activated partial thromboplastin time (APTT) [ Time Frame: At the end of 8 hour infusion of study drug ]
  • Coagulation assessed by activated partial thromboplastin time (APTT) [ Time Frame: 24 hours after pre-hospital dose of study drug ]
  • Platelet count [ Time Frame: Immediately upon patient arrival to hospital ]
  • Platelet count [ Time Frame: At the end of 8 hour infusion of study drug ]
  • Platelet count [ Time Frame: 24 hours after pre-hospital dose of study drug ]
  • Vascular occlusive events (myocardial infarction, stroke, deep venous thrombosis (DVT), pulmonary embolus (PE)) [ Time Frame: Hospital discharge (or up to 28 days in hospital) ]
  • Ventilator-free days [ Time Frame: 28 days ]
  • Mortality [ Time Frame: 24 hours ]
  • Mortality [ Time Frame: 28 days ]
  • Mortality [ Time Frame: 6 months ]
  • Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury [ Time Frame: 24 hours ]
  • Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury [ Time Frame: 28 days ]
  • Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury [ Time Frame: 6 months ]
  • Cumulative incidence of sepsis [ Time Frame: Hospital discharge (or up to 28 days in hospital) ]
  • Quality of life measured using WHODAS 2.0 [ Time Frame: 6 months ]
  • Quality of life measured using the EuroQOL 5 dimensions questionnaire (EQ-5D) [ Time Frame: 6 months ]
  • Number of participants with serious adverse events [ Time Frame: hospital discharge (or up to 28 days in hospital) ]
  • Coagulation assessed by fibrinogen [ Time Frame: Immediately upon patient arrival to hospital ]
  • Coagulation assessed by fibrinogen [ Time Frame: At the end of 8 hour infusion of study drug ]
  • Coagulation assessed by fibrinogen [ Time Frame: 24 hours after pre-hospital dose of study drug ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2014)
  • Units of blood products used (red blood cells, plasma, platelets, prothrombin complex concentrate, fibrinogen, Factor VIIa, cryoprecipitate) [ Time Frame: 24 hours ]
  • Coagulation assessed using the international normalised ratio (INR) [ Time Frame: On patient arrival to hospital ]
  • Coagulation assessed using the international normalised ratio (INR) [ Time Frame: At the end of 8 hour infusion of study drug ]
  • Coagulation assessed using the international normalised ratio (INR) [ Time Frame: 24 hours after pre-hospital dose of study drug ]
  • Coagulation assessed by activated partial thromboplastin time (APTT) [ Time Frame: On patient arrival to hospital ]
  • Coagulation assessed by activated partial thromboplastin time (APTT) [ Time Frame: At the end of 8 hour infusion of study drug ]
  • Coagulation assessed by activated partial thromboplastin time (APTT) [ Time Frame: 24 hours after pre-hospital dose of study drug ]
  • Platelet count [ Time Frame: On patient arrival to hospital ]
  • Platelet count [ Time Frame: At the end of 8 hour infusion of study drug ]
  • Platelet count [ Time Frame: 24 hours after pre-hospital dose of study drug ]
  • Vascular occlusive events (myocardial infarction, stroke, deep venous thrombosis (DVT), pulmonary embolus (PE)) [ Time Frame: Hospital discharge (or up to 28 days in hospital) ]
  • Ventilator-free days [ Time Frame: 28 days ]
  • Mortality [ Time Frame: 24 hours ]
  • Mortality [ Time Frame: 28 days ]
  • Mortality [ Time Frame: 6 months ]
  • Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury [ Time Frame: 24 hours ]
  • Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury [ Time Frame: 28 days ]
  • Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury [ Time Frame: 6 months ]
  • Cumulative incidence of sepsis [ Time Frame: Hospital discharge (or up to 28 days in hospital) ]
  • Pain measured using the modified Brief Pain Inventory (mBPI) [ Time Frame: 6 months ]
  • Quality of life measured using the 12-item short form health survey (SF12®) [ Time Frame: 6 months ]
  • Quality of life measured using the EuroQOL 5 dimensions questionnaire (EQ-5D) [ Time Frame: 6 months ]
  • Number of participants with serious adverse events [ Time Frame: hospital discharge (or up to 28 days in hospital) ]
Current Other Pre-specified Outcome Measures
 (submitted: June 6, 2016)
  • Blood lactate concentration [ Time Frame: Immediately upon patient arrival to hospital ]
  • Laboratory analysis of fibrinolytic activity [ Time Frame: At the end of 8 hour infusion of study drug ]
  • Laboratory analysis of fibrinolytic activity [ Time Frame: 24 hours after first (prehospital) dose of study drug ]
  • Laboratory analysis of plasmin/anti-plasmin complexes [ Time Frame: At the end of 8 hour infusion of study drug ]
  • Laboratory analysis of plasmin/anti-plasmin complexes [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
  • Laboratory analysis of tissue type plasminogen activator (tPA) [ Time Frame: At the end of 8 hour infusion of study drug ]
  • Laboratory analysis of tissue type plasminogen activator (tPA) [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
  • Laboratory analysis of plasminogen activator inhibitor 1 (PAI-1) [ Time Frame: At the end of 8 hour infusion of study drug ]
  • Laboratory analysis of plasminogen activator inhibitor 1 (PAI-1) [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
  • Laboratory analysis of t-PA/PAI-1 complexes [ Time Frame: At the end of 8 hour infusion of study drug ]
    Substudy
  • Laboratory analysis of t-PA/PAI-1 complexes [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
    Substudy
  • Laboratory analysis of thrombin activatable fibrinolysis inhibitor (TAFI) [ Time Frame: At the end of 8 hour infusion of study drug ]
    Substudy
  • Laboratory analysis of thrombin activatable fibrinolysis inhibitor (TAFI) [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
    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 ]
    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 ]
    Substudy
  • Laboratory analysis of granulocyte macrophage colony-stimulating factor (GM-CSF) [ Time Frame: At the end of 8 hour infusion of study drug ]
    Substudy
  • Laboratory analysis of granulocyte macrophage colony-stimulating factor (GM-CSF) [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
    Substudy
  • Laboratory analysis of interferon gamma [ Time Frame: At the end of 8 hour infusion of study drug ]
    Substudy
  • Laboratory analysis of interferon gamma [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
    Substudy
  • Laboratory analysis of tumour necrosis factor alpha [ Time Frame: At the end of 8 hour infusion of study drug ]
    Substudy
  • Laboratory analysis of tumour necrosis factor alpha [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
    Substudy
  • TXA concentration in blood [ Time Frame: 8 hours after first dose of study drug ]
    substudy
  • TXA concentration in blood [ Time Frame: 24 hours after first dose of study drug ]
    substudy
Original Other Pre-specified Outcome Measures
 (submitted: July 9, 2014)
  • Blood lactate concentration [ Time Frame: On patient arrival to hospital ]
  • Laboratory analysis of fibrinolytic activity [ Time Frame: At the end of 8 hour infusion of study drug ]
  • Laboratory analysis of fibrinolytic activity [ Time Frame: 24 hours after first (prehospital) dose of study drug ]
  • Laboratory analysis of plasmin/anti-plasmin complexes [ Time Frame: At the end of 8 hour infusion of study drug ]
  • Laboratory analysis of plasmin/anti-plasmin complexes [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
  • Laboratory analysis of tissue type plasminogen activator (tPA) [ Time Frame: At the end of 8 hour infusion of study drug ]
  • Laboratory analysis of tissue type plasminogen activator (tPA) [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
  • Laboratory analysis of plasminogen activator inhibitor 1 (PAI-1) [ Time Frame: At the end of 8 hour infusion of study drug ]
  • Laboratory analysis of plasminogen activator inhibitor 1 (PAI-1) [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
  • Laboratory analysis of t-PA/PAI-1 complexes [ Time Frame: At the end of 8 hour infusion of study drug ]
    Substudy
  • Laboratory analysis of t-PA/PAI-1 complexes [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
    Substudy
  • Laboratory analysis of thrombin activatable fibrinolysis inhibitor (TAFI) [ Time Frame: At the end of 8 hour infusion of study drug ]
    Substudy
  • Laboratory analysis of thrombin activatable fibrinolysis inhibitor (TAFI) [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
    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 ]
    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 ]
    Substudy
  • Laboratory analysis of granulocyte macrophage colony-stimulating factor (GM-CSF) [ Time Frame: At the end of 8 hour infusion of study drug ]
    Substudy
  • Laboratory analysis of granulocyte macrophage colony-stimulating factor (GM-CSF) [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
    Substudy
  • Laboratory analysis of interferon gamma [ Time Frame: At the end of 8 hour infusion of study drug ]
    Substudy
  • Laboratory analysis of interferon gamma [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
    Substudy
  • Laboratory analysis of tumour necrosis factor alpha [ Time Frame: At the end of 8 hour infusion of study drug ]
    Substudy
  • Laboratory analysis of tumour necrosis factor alpha [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
    Substudy
  • TXA concentration in blood [ Time Frame: 8 hours after first dose of study drug ]
    substudy
  • TXA concentration in blood [ Time Frame: 24 hours after first dose of study drug ]
    substudy
 
Descriptive Information
Brief Title  ICMJE Pre-hospital Anti-fibrinolytics for Traumatic Coagulopathy and Haemorrhage (The PATCH Study)
Official Title  ICMJE 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.
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Wounds and Injuries
  • Acute Coagulopathy
Intervention  ICMJE
  • 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
  • Drug: Placebo
Study Arms  ICMJE
  • 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.

    Intervention: Drug: Tranexamic Acid
  • 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.

    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 9, 2014)
1184
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2021
Estimated Primary Completion Date January 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Veronica Pitt, PhD +613 9903 0343 veronica.pitt@monash.edu
Listed Location Countries  ICMJE Australia,   New Zealand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02187120
Other Study ID Numbers  ICMJE APP1044894
U1111-1160-6738 ( Other Identifier: WHO Universal Trial Number (UTN) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Russell Gruen, Monash University
Study Sponsor  ICMJE Monash University
Collaborators  ICMJE
  • National Health and Medical Research Council, Australia
  • Health Research Council, New Zealand
Investigators  ICMJE
Principal Investigator: Russell L Gruen, MBBS PhD Monash University
PRS Account Monash University
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP