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

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Wounds and Injuries, Acute Coagulopathy

Intervention / Treatment
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* Drug: Tranexamic Acid
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tranexamic Acid<br>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<br>* 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.<br>* Other names: Cyklokapron;|
| Placebo Comparator: Placebo<br>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<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| Ventilator-free days |  | 28 days | 
| Mortality |  | 24 hours | 
| Mortality |  | 28 days | 
| Mortality |  | 6 months | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Wounds and Injuries, Acute Coagulopathy, Tranexamic Acid, Emergency Medical Services