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

• ClinicalTrials.gov Identifier: NCT02187120
• Recruitment Status: Completed
• First Posted: July 10, 2014
• Last Update Posted: January 27, 2023
• Sponsor: Monash University
• Collaborators: National Health and Medical Research Council, Australia; Health Research Council, New Zealand
• Information provided by (Responsible Party): Russell Gruen, Monash University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Wounds and Injuries; Acute Coagulopathy	Drug: Tranexamic Acid; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1310 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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.
• Actual Study Start Date: July 28, 2014
• Actual Primary Completion Date: May 9, 2022
• Actual Study Completion Date: September 7, 2022

Arms and Interventions

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 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

Outcome Measures

Primary Outcome Measures :

1. 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 ]

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Blood lactate concentration [ Time Frame: Immediately upon patient arrival to hospital ]
2. Laboratory analysis of fibrinolytic activity [ Time Frame: At the end of 8 hour infusion of study drug ]
3. Laboratory analysis of fibrinolytic activity [ Time Frame: 24 hours after first (prehospital) dose of study drug ]
4. Laboratory analysis of plasmin/anti-plasmin complexes [ Time Frame: At the end of 8 hour infusion of study drug ]
5. Laboratory analysis of plasmin/anti-plasmin complexes [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
6. Laboratory analysis of tissue type plasminogen activator (tPA) [ Time Frame: At the end of 8 hour infusion of study drug ]
7. Laboratory analysis of tissue type plasminogen activator (tPA) [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
8. Laboratory analysis of plasminogen activator inhibitor 1 (PAI-1) [ Time Frame: At the end of 8 hour infusion of study drug ]
9. Laboratory analysis of plasminogen activator inhibitor 1 (PAI-1) [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
10. Laboratory analysis of t-PA/PAI-1 complexes [ Time Frame: At the end of 8 hour infusion of study drug ]
    Substudy
11. Laboratory analysis of t-PA/PAI-1 complexes [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
    Substudy
12. Laboratory analysis of thrombin activatable fibrinolysis inhibitor (TAFI) [ Time Frame: At the end of 8 hour infusion of study drug ]
    Substudy
13. Laboratory analysis of thrombin activatable fibrinolysis inhibitor (TAFI) [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
    Substudy
14. 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
15. 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
16. Laboratory analysis of granulocyte macrophage colony-stimulating factor (GM-CSF) [ Time Frame: At the end of 8 hour infusion of study drug ]
    Substudy
17. Laboratory analysis of granulocyte macrophage colony-stimulating factor (GM-CSF) [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
    Substudy
18. Laboratory analysis of interferon gamma [ Time Frame: At the end of 8 hour infusion of study drug ]
    Substudy
19. Laboratory analysis of interferon gamma [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
    Substudy
20. Laboratory analysis of tumour necrosis factor alpha [ Time Frame: At the end of 8 hour infusion of study drug ]
    Substudy
21. Laboratory analysis of tumour necrosis factor alpha [ Time Frame: 24 hours after first (pre-hospital) dose of study drug ]
    Substudy
22. TXA concentration in blood [ Time Frame: 8 hours after first dose of study drug ]
    substudy
23. TXA concentration in blood [ Time Frame: 24 hours after first dose of study drug ]
    substudy

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

Australia, New South Wales

Lismore Base Hospital

Lismore, New South Wales, Australia, 2480

NNSW Medical Retrieval Service

Lismore, New South Wales, Australia, 2480

John Hunter Hospital

Newcastle, New South Wales, Australia, 2305

CareFlight

Northmead, New South Wales, Australia, 2152

Orange Base Hospital

Orange, New South Wales, Australia, 2800

Ambulance Service of New South Wales

Rozelle, New South Wales, Australia, 2039

Royal North Shore Hospital

St Leonards, New South Wales, Australia, 2065

Liverpool Hospital

Sydney, New South Wales, Australia, 2170

Wagga Wagga Base Hospital

Wagga Wagga, New South Wales, Australia, 2650

Westmead Hospital

Westmead, New South Wales, Australia, 2145

Australia, Northern Territory

St John Ambulance

Darwin, Northern Territory, Australia, 0810

Royal Darwin Hospital

Darwin, Northern Territory, Australia, 0811

Australia, Queensland

Royal Brisbane and Women's Hospital

Brisbane, Queensland, Australia, 4006

Princess Alexandra Hospital

Brisbane, Queensland, Australia, 4102

Gold Coast Hospital

Gold Coast, Queensland, Australia, 4215

Queensland Ambulance Service

Kedron, Queensland, Australia, 4031

Australia, South Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia, 5000

Flinders Medical Centre

Bedford Park, South Australia, Australia, 5042

South Australia Ambulance Service

Eastwood, South Australia, Australia, 5063

Australia, Tasmania

Ambulance Tasmania

Hobart, Tasmania, Australia, 7000

Royal Hobart Hospital

Hobart, Tasmania, Australia, 7000

Australia, Victoria

Ambulance Victoria

Melbourne, Victoria, Australia, 2000

The Alfred Hospital

Melbourne, Victoria, Australia, 3004

Royal Melbourne Hospital

Melbourne, Victoria, Australia, 3050

Australia, Western Australia

St John Ambulance Western Australia

Geraldton, Western Australia, Australia, 6530

Royal Perth Hospital

Perth, Western Australia, Australia, 6000

New Zealand

St John Ambulance

Albany, New Zealand, 0632

Auckland City Hospital

Auckland, New Zealand, 1142

Middlemore Hospital

Auckland, New Zealand, 2025

Waikato Hospital

Hamilton West, New Zealand, 3204

Hawke's Bay

Hastings, New Zealand, 4156

Wellington Free Ambulance

Wellington, New Zealand, 6011

Wellington Hospital

Wellington, New Zealand, 6021

Sponsors and Collaborators

Monash University

National Health and Medical Research Council, Australia

Health Research Council, New Zealand

Investigators

• Principal Investigator: Russell L Gruen, MBBS PhD; Monash University

More Information

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Russell Gruen, Professor of Surgery and Public Health, Monash University
• ClinicalTrials.gov Identifier: NCT02187120
• Other Study ID Numbers: APP1044894; U1111-1160-6738 ( Other Identifier: WHO Universal Trial Number (UTN) )
• First Posted: July 10, 2014
• Last Update Posted: January 27, 2023
• Last Verified: January 2023

Keywords provided by Russell Gruen, Monash University:

Wounds and Injuries; Acute Coagulopathy; Tranexamic Acid; Emergency Medical Services

Additional relevant MeSH terms:

Hemostatic Disorders; Blood Coagulation Disorders; Wounds and Injuries; Hematologic Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Tranexamic Acid; Antifibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Hemostatics; Coagulants