Clinical trial NCT02187120: Pre-hospital Anti-fibrinolytics for Traumatic Coagulopathy and Haemorrhage (The PATCH Study)
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Wounds and Injuries
Acute Coagulopathy
Keywords: Wounds and Injuries
Acute Coagulopathy
Tranexamic Acid
Emergency Medical Services
Lead sponsor: Monash University
Sponsor class: OTHER
Collaborators: name: National Health and Medical Research Council, Australia
name: Health Research Council, New Zealand
First posted: 2014-07-10
Enrollment: 1310
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
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).
timeFrame: 6 months
Secondary outcomes:
measure: Units of blood products used (red blood cells, plasma, platelets, prothrombin complex concentrate, fibrinogen, Factor VIIa, cryoprecipitate)
timeFrame: 24 hours
measure: Coagulation assessed using the international normalised ratio (INR)
timeFrame: Immediately upon patient arrival to hospital
measure: Coagulation assessed using the international normalised ratio (INR)
timeFrame: At the end of 8 hour infusion of study drug
measure: Coagulation assessed using the international normalised ratio (INR)
timeFrame: 24 hours after pre-hospital dose of study drug
measure: Coagulation assessed by activated partial thromboplastin time (APTT)
timeFrame: Immediately upon patient arrival to hospital
measure: Coagulation assessed by activated partial thromboplastin time (APTT)
timeFrame: At the end of 8 hour infusion of study drug
measure: Coagulation assessed by activated partial thromboplastin time (APTT)
timeFrame: 24 hours after pre-hospital dose of study drug
measure: Platelet count
timeFrame: Immediately upon patient arrival to hospital
measure: Platelet count
timeFrame: At the end of 8 hour infusion of study drug
measure: Platelet count
timeFrame: 24 hours after pre-hospital dose of study drug
measure: Vascular occlusive events (myocardial infarction, stroke, deep venous thrombosis (DVT), pulmonary embolus (PE))
timeFrame: Hospital discharge (or up to 28 days in hospital)
measure: Ventilator-free days
timeFrame: 28 days
measure: Mortality
timeFrame: 24 hours
measure: Mortality
timeFrame: 28 days
measure: Mortality
timeFrame: 6 months
measure: Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury
timeFrame: 24 hours
measure: Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury
timeFrame: 28 days
measure: Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury
timeFrame: 6 months
measure: Cumulative incidence of sepsis
timeFrame: Hospital discharge (or up to 28 days in hospital)
measure: Quality of life measured using WHODAS 2.0
timeFrame: 6 months
measure: Quality of life measured using the EuroQOL 5 dimensions questionnaire (EQ-5D)
timeFrame: 6 months
measure: Number of participants with serious adverse events
timeFrame: hospital discharge (or up to 28 days in hospital)
measure: Coagulation assessed by fibrinogen
timeFrame: Immediately upon patient arrival to hospital
measure: Coagulation assessed by fibrinogen
timeFrame: At the end of 8 hour infusion of study drug
measure: Coagulation assessed by fibrinogen
timeFrame: 24 hours after pre-hospital dose of study drug
Other outcomes:
measure: Blood lactate concentration
timeFrame: Immediately upon patient arrival to hospital
measure: Laboratory analysis of fibrinolytic activity
timeFrame: At the end of 8 hour infusion of study drug
measure: Laboratory analysis of fibrinolytic activity
timeFrame: 24 hours after first (prehospital) dose of study drug
measure: Laboratory analysis of plasmin/anti-plasmin complexes
timeFrame: At the end of 8 hour infusion of study drug
measure: Laboratory analysis of plasmin/anti-plasmin complexes
timeFrame: 24 hours after first (pre-hospital) dose of study drug
measure: Laboratory analysis of tissue type plasminogen activator (tPA)
timeFrame: At the end of 8 hour infusion of study drug
measure: Laboratory analysis of tissue type plasminogen activator (tPA)
timeFrame: 24 hours after first (pre-hospital) dose of study drug
measure: Laboratory analysis of plasminogen activator inhibitor 1 (PAI-1)
timeFrame: At the end of 8 hour infusion of study drug
measure: Laboratory analysis of plasminogen activator inhibitor 1 (PAI-1)
timeFrame: 24 hours after first (pre-hospital) dose of study drug
measure: Laboratory analysis of t-PA/PAI-1 complexes
timeFrame: At the end of 8 hour infusion of study drug
measure: Laboratory analysis of t-PA/PAI-1 complexes
timeFrame: 24 hours after first (pre-hospital) dose of study drug
measure: Laboratory analysis of thrombin activatable fibrinolysis inhibitor (TAFI)
timeFrame: At the end of 8 hour infusion of study drug
measure: Laboratory analysis of thrombin activatable fibrinolysis inhibitor (TAFI)
timeFrame: 24 hours after first (pre-hospital) dose of study drug
measure: Laboratory analysis of interleukins (IL-2, IL-4, IL-6, IL-8, IL-10)
timeFrame: At the end of 8 hour infusion of study drug
measure: Laboratory analysis of interleukins (IL-2, IL-4, IL-6, IL-8, IL-10)
timeFrame: 24 hours after first (pre-hospital) dose of study drug
measure: Laboratory analysis of granulocyte macrophage colony-stimulating factor (GM-CSF)
timeFrame: At the end of 8 hour infusion of study drug
measure: Laboratory analysis of granulocyte macrophage colony-stimulating factor (GM-CSF)
timeFrame: 24 hours after first (pre-hospital) dose of study drug
measure: Laboratory analysis of interferon gamma
timeFrame: At the end of 8 hour infusion of study drug
measure: Laboratory analysis of interferon gamma
timeFrame: 24 hours after first (pre-hospital) dose of study drug
measure: Laboratory analysis of tumour necrosis factor alpha
timeFrame: At the end of 8 hour infusion of study drug
measure: Laboratory analysis of tumour necrosis factor alpha
timeFrame: 24 hours after first (pre-hospital) dose of study drug
measure: TXA concentration in blood
timeFrame: 8 hours after first dose of study drug
measure: TXA concentration in blood
timeFrame: 24 hours after first dose of study drug
Locations:
city: Lismore
country: Australia
facility: Lismore Base Hospital
state: New South Wales
city: Lismore
country: Australia
facility: NNSW Medical Retrieval Service
state: New South Wales
city: Newcastle
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Northmead
country: Australia
facility: CareFlight
state: New South Wales
city: Orange
country: Australia
facility: Orange Base Hospital
state: New South Wales
city: Rozelle
country: Australia
facility: Ambulance Service of New South Wales
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Wagga Wagga
country: Australia
facility: Wagga Wagga Base Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Darwin
country: Australia
facility: St John Ambulance
state: Northern Territory
city: Darwin
country: Australia
facility: Royal Darwin Hospital
state: Northern Territory
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Gold Coast
country: Australia
facility: Gold Coast Hospital
state: Queensland
city: Kedron
country: Australia
facility: Queensland Ambulance Service
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Eastwood
country: Australia
facility: South Australia Ambulance Service
state: South Australia
city: Hobart
country: Australia
facility: Ambulance Tasmania
state: Tasmania
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Melbourne
country: Australia
facility: Ambulance Victoria
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Geraldton
country: Australia
facility: St John Ambulance Western Australia
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Albany
country: New Zealand
facility: St John Ambulance
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Auckland
country: New Zealand
facility: Middlemore Hospital
city: Hamilton West
country: New Zealand
facility: Waikato Hospital
city: Hastings
country: New Zealand
facility: Hawke's Bay
city: Wellington
country: New Zealand
facility: Wellington Free Ambulance
city: Wellington
country: New Zealand
facility: Wellington Hospital
Study officials:
affiliation: Monash University
name: Russell L Gruen, MBBS PhD
role: PRINCIPAL_INVESTIGATOR
References:
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: 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: 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: 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: 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: 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.