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

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.

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.

Study Overview

• Status: Completed
• Conditions: Wounds and Injuries; Acute Coagulopathy
• Intervention / Treatment: Drug: Placebo; Drug: Tranexamic Acid

• Study Type: Interventional
• Enrollment (Actual): 1310
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Camila Battistuzzo, PhD; Phone Number: 0399030391; Email: camila.battistuzzo@monash.edu

Study Locations

• Australia
  • New South Wales
    • Lismore, New South Wales, Australia, 2480
      • Lismore Base Hospital
    • Lismore, New South Wales, Australia, 2480
      • NNSW Medical Retrieval Service
    • Newcastle, New South Wales, Australia, 2305
      • John Hunter Hospital
    • Northmead, New South Wales, Australia, 2152
      • CareFlight
    • Orange, New South Wales, Australia, 2800
      • Orange Base Hospital
    • Rozelle, New South Wales, Australia, 2039
      • Ambulance Service of New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
    • Sydney, New South Wales, Australia, 2170
      • Liverpool Hospital
    • Wagga Wagga, New South Wales, Australia, 2650
      • Wagga Wagga Base Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Northern Territory
    • Darwin, Northern Territory, Australia, 0810
      • St John Ambulance
    • Darwin, Northern Territory, Australia, 0811
      • Royal Darwin Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Princess Alexandra Hospital
    • Brisbane, Queensland, Australia, 4006
      • Royal Brisbane and Women'S Hospital
    • Gold Coast, Queensland, Australia, 4215
      • Gold Coast Hospital
    • Kedron, Queensland, Australia, 4031
      • Queensland Ambulance Service
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
    • Eastwood, South Australia, Australia, 5063
      • South Australia Ambulance Service
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
    • Hobart, Tasmania, Australia, 7000
      • Ambulance Tasmania
  • Victoria
    • Melbourne, Victoria, Australia, 3050
      • Royal Melbourne Hospital
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
    • Melbourne, Victoria, Australia, 2000
      • Ambulance Victoria
  • Western Australia
    • Geraldton, Western Australia, Australia, 6530
      • St John Ambulance Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
• New Zealand
  • Albany, New Zealand, 0632
    • St John Ambulance
  • Auckland, New Zealand, 1142
    • Auckland City Hospital
  • Auckland, New Zealand, 2025
    • Middlemore Hospital
  • Hamilton West, New Zealand, 3204
    • Waikato Hospital
  • Hastings, New Zealand, 4156
    • Hawke's Bay
  • Wellington, New Zealand, 6021
    • Wellington Hospital
  • Wellington, New Zealand, 6011
    • Wellington Free Ambulance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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).	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Mortality	28 days
Ventilator-free days	28 days
Mortality	6 months
Units of blood products used (red blood cells, plasma, platelets, prothrombin complex concentrate, fibrinogen, Factor VIIa, cryoprecipitate)	24 hours
Coagulation assessed using the international normalised ratio (INR)	Immediately upon patient arrival to hospital
Coagulation assessed using the international normalised ratio (INR)	At the end of 8 hour infusion of study drug
Coagulation assessed using the international normalised ratio (INR)	24 hours after pre-hospital dose of study drug
Coagulation assessed by activated partial thromboplastin time (APTT)	Immediately upon patient arrival to hospital
Coagulation assessed by activated partial thromboplastin time (APTT)	At the end of 8 hour infusion of study drug
Coagulation assessed by activated partial thromboplastin time (APTT)	24 hours after pre-hospital dose of study drug
Platelet count	Immediately upon patient arrival to hospital
Platelet count	At the end of 8 hour infusion of study drug
Platelet count	24 hours after pre-hospital dose of study drug
Vascular occlusive events (myocardial infarction, stroke, deep venous thrombosis (DVT), pulmonary embolus (PE))	Hospital discharge (or up to 28 days in hospital)
Mortality	24 hours
Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury	24 hours
Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury	28 days
Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury	6 months
Cumulative incidence of sepsis	Hospital discharge (or up to 28 days in hospital)
Quality of life measured using WHODAS 2.0	6 months
Quality of life measured using the EuroQOL 5 dimensions questionnaire (EQ-5D)	6 months
Number of participants with serious adverse events	hospital discharge (or up to 28 days in hospital)
Coagulation assessed by fibrinogen	Immediately upon patient arrival to hospital
Coagulation assessed by fibrinogen	At the end of 8 hour infusion of study drug
Coagulation assessed by fibrinogen	24 hours after pre-hospital dose of study drug

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood lactate concentration		Immediately upon patient arrival to hospital
Laboratory analysis of fibrinolytic activity		At the end of 8 hour infusion of study drug
Laboratory analysis of fibrinolytic activity		24 hours after first (prehospital) dose of study drug
Laboratory analysis of plasmin/anti-plasmin complexes		At the end of 8 hour infusion of study drug
Laboratory analysis of plasmin/anti-plasmin complexes		24 hours after first (pre-hospital) dose of study drug
Laboratory analysis of tissue type plasminogen activator (tPA)		At the end of 8 hour infusion of study drug
Laboratory analysis of tissue type plasminogen activator (tPA)		24 hours after first (pre-hospital) dose of study drug
Laboratory analysis of plasminogen activator inhibitor 1 (PAI-1)		At the end of 8 hour infusion of study drug
Laboratory analysis of plasminogen activator inhibitor 1 (PAI-1)		24 hours after first (pre-hospital) dose of study drug
Laboratory analysis of t-PA/PAI-1 complexes	Substudy	At the end of 8 hour infusion of study drug
Laboratory analysis of t-PA/PAI-1 complexes	Substudy	24 hours after first (pre-hospital) dose of study drug
Laboratory analysis of thrombin activatable fibrinolysis inhibitor (TAFI)	Substudy	At the end of 8 hour infusion of study drug
Laboratory analysis of thrombin activatable fibrinolysis inhibitor (TAFI)	Substudy	24 hours after first (pre-hospital) dose of study drug
Laboratory analysis of interleukins (IL-2, IL-4, IL-6, IL-8, IL-10)	Substudy	At the end of 8 hour infusion of study drug
Laboratory analysis of interleukins (IL-2, IL-4, IL-6, IL-8, IL-10)	Substudy	24 hours after first (pre-hospital) dose of study drug
Laboratory analysis of granulocyte macrophage colony-stimulating factor (GM-CSF)	Substudy	At the end of 8 hour infusion of study drug
Laboratory analysis of granulocyte macrophage colony-stimulating factor (GM-CSF)	Substudy	24 hours after first (pre-hospital) dose of study drug
Laboratory analysis of interferon gamma	Substudy	At the end of 8 hour infusion of study drug
Laboratory analysis of interferon gamma	Substudy	24 hours after first (pre-hospital) dose of study drug
Laboratory analysis of tumour necrosis factor alpha	Substudy	At the end of 8 hour infusion of study drug
Laboratory analysis of tumour necrosis factor alpha	Substudy	24 hours after first (pre-hospital) dose of study drug
TXA concentration in blood	substudy	8 hours after first dose of study drug
TXA concentration in blood	substudy	24 hours after first dose of study drug

Collaborators and Investigators

• Sponsor: Monash University
• Collaborators: National Health and Medical Research Council, Australia; Health Research Council, New Zealand
• Investigators: Principal Investigator: Russell L Gruen, MBBS PhD, Monash University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• Mitra B, Bernard S, Gantner D, Burns B, Reade MC, Murray L, Trapani T, Pitt V, McArthur C, Forbes A, Maegele M, Gruen RL; PATCH-Trauma study investigators; PATCH-Trauma Study investigators. Protocol for a multicentre prehospital randomised controlled trial investigating tranexamic acid in severe trauma: the PATCH-Trauma trial. BMJ Open. 2021 Mar 15;11(3):e046522. doi: 10.1136/bmjopen-2020-046522.

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2014
• Primary Completion (Actual): May 9, 2022
• Study Completion (Actual): September 7, 2022

Study Registration Dates

• First Submitted: July 8, 2014
• First Submitted That Met QC Criteria: July 9, 2014
• First Posted (Estimate): July 10, 2014

Study Record Updates

• Last Update Posted (Actual): January 27, 2023
• Last Update Submitted That Met QC Criteria: January 26, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Emergency Medical Services; Wounds and Injuries; Tranexamic Acid; Acute Coagulopathy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Blood Coagulation Disorders; Wounds and Injuries; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: APP1044894; U1111-1160-6738 (Other Identifier: WHO Universal Trial Number (UTN))