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

Wounds and Injuries Clinical Trial

— PATCH  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02187120
• Other study ID #: APP1044894
• Secondary ID: U1111-1160-6738
• Status: Completed
• Phase: Phase 3
• Start date: July 28, 2014
• Est. completion date: September 7, 2022

Study information

• Verified date: January 2023
• Source: Monash University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1310
• Est. completion date: September 7, 2022
• Est. primary completion date: May 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Coagulopathy
• Blood Coagulation Disorders
• Hemostatic Disorders
• Wounds and Injuries

Intervention

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.
• Placebo

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Royal Brisbane and Women's Hospital	Brisbane	Queensland
Australia	Royal Darwin Hospital	Darwin	Northern Territory
Australia	St John Ambulance	Darwin	Northern Territory
Australia	South Australia Ambulance Service	Eastwood	South Australia
Australia	St John Ambulance Western Australia	Geraldton	Western Australia
Australia	Gold Coast Hospital	Gold Coast	Queensland
Australia	Ambulance Tasmania	Hobart	Tasmania
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Queensland Ambulance Service	Kedron	Queensland
Australia	Lismore Base Hospital	Lismore	New South Wales
Australia	NNSW Medical Retrieval Service	Lismore	New South Wales
Australia	Ambulance Victoria	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	John Hunter Hospital	Newcastle	New South Wales
Australia	CareFlight	Northmead	New South Wales
Australia	Orange Base Hospital	Orange	New South Wales
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Ambulance Service of New South Wales	Rozelle	New South Wales
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Australia	Liverpool Hospital	Sydney	New South Wales
Australia	Wagga Wagga Base Hospital	Wagga Wagga	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
New Zealand	St John Ambulance	Albany
New Zealand	Auckland City Hospital	Auckland
New Zealand	Middlemore Hospital	Auckland
New Zealand	Waikato Hospital	Hamilton West
New Zealand	Hawke's Bay	Hastings
New Zealand	Wellington Free Ambulance	Wellington
New Zealand	Wellington Hospital	Wellington

Sponsors (3)

Lead Sponsor	Collaborator
Monash University	Health Research Council, New Zealand, National Health and Medical Research Council, Australia

Countries where clinical trial is conducted

Australia,  New Zealand, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Blood lactate concentration		Immediately upon patient arrival to hospital
Other	Laboratory analysis of fibrinolytic activity		At the end of 8 hour infusion of study drug
Other	Laboratory analysis of fibrinolytic activity		24 hours after first (prehospital) dose of study drug
Other	Laboratory analysis of plasmin/anti-plasmin complexes		At the end of 8 hour infusion of study drug
Other	Laboratory analysis of plasmin/anti-plasmin complexes		24 hours after first (pre-hospital) dose of study drug
Other	Laboratory analysis of tissue type plasminogen activator (tPA)		At the end of 8 hour infusion of study drug
Other	Laboratory analysis of tissue type plasminogen activator (tPA)		24 hours after first (pre-hospital) dose of study drug
Other	Laboratory analysis of plasminogen activator inhibitor 1 (PAI-1)		At the end of 8 hour infusion of study drug
Other	Laboratory analysis of plasminogen activator inhibitor 1 (PAI-1)		24 hours after first (pre-hospital) dose of study drug
Other	Laboratory analysis of t-PA/PAI-1 complexes	Substudy	At the end of 8 hour infusion of study drug
Other	Laboratory analysis of t-PA/PAI-1 complexes	Substudy	24 hours after first (pre-hospital) dose of study drug
Other	Laboratory analysis of thrombin activatable fibrinolysis inhibitor (TAFI)	Substudy	At the end of 8 hour infusion of study drug
Other	Laboratory analysis of thrombin activatable fibrinolysis inhibitor (TAFI)	Substudy	24 hours after first (pre-hospital) dose of study drug
Other	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
Other	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
Other	Laboratory analysis of granulocyte macrophage colony-stimulating factor (GM-CSF)	Substudy	At the end of 8 hour infusion of study drug
Other	Laboratory analysis of granulocyte macrophage colony-stimulating factor (GM-CSF)	Substudy	24 hours after first (pre-hospital) dose of study drug
Other	Laboratory analysis of interferon gamma	Substudy	At the end of 8 hour infusion of study drug
Other	Laboratory analysis of interferon gamma	Substudy	24 hours after first (pre-hospital) dose of study drug
Other	Laboratory analysis of tumour necrosis factor alpha	Substudy	At the end of 8 hour infusion of study drug
Other	Laboratory analysis of tumour necrosis factor alpha	Substudy	24 hours after first (pre-hospital) dose of study drug
Other	TXA concentration in blood	substudy	8 hours after first dose of study drug
Other	TXA concentration in blood	substudy	24 hours after first dose of study drug
Primary	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	Units of blood products used (red blood cells, plasma, platelets, prothrombin complex concentrate, fibrinogen, Factor VIIa, cryoprecipitate)		24 hours
Secondary	Coagulation assessed using the international normalised ratio (INR)		Immediately upon patient arrival to hospital
Secondary	Coagulation assessed using the international normalised ratio (INR)		At the end of 8 hour infusion of study drug
Secondary	Coagulation assessed using the international normalised ratio (INR)		24 hours after pre-hospital dose of study drug
Secondary	Coagulation assessed by activated partial thromboplastin time (APTT)		Immediately upon patient arrival to hospital
Secondary	Coagulation assessed by activated partial thromboplastin time (APTT)		At the end of 8 hour infusion of study drug
Secondary	Coagulation assessed by activated partial thromboplastin time (APTT)		24 hours after pre-hospital dose of study drug
Secondary	Platelet count		Immediately upon patient arrival to hospital
Secondary	Platelet count		At the end of 8 hour infusion of study drug
Secondary	Platelet count		24 hours after pre-hospital dose of study drug
Secondary	Vascular occlusive events (myocardial infarction, stroke, deep venous thrombosis (DVT), pulmonary embolus (PE))		Hospital discharge (or up to 28 days in hospital)
Secondary	Ventilator-free days		28 days
Secondary	Mortality		24 hours
Secondary	Mortality		28 days
Secondary	Mortality		6 months
Secondary	Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury		24 hours
Secondary	Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury		28 days
Secondary	Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury		6 months
Secondary	Cumulative incidence of sepsis		Hospital discharge (or up to 28 days in hospital)
Secondary	Quality of life measured using WHODAS 2.0		6 months
Secondary	Quality of life measured using the EuroQOL 5 dimensions questionnaire (EQ-5D)		6 months
Secondary	Number of participants with serious adverse events		hospital discharge (or up to 28 days in hospital)
Secondary	Coagulation assessed by fibrinogen		Immediately upon patient arrival to hospital
Secondary	Coagulation assessed by fibrinogen		At the end of 8 hour infusion of study drug
Secondary	Coagulation assessed by fibrinogen		24 hours after pre-hospital dose of study drug