Acute Coagulopathy, Wounds and Injuries
Conditions
Keywords
Wounds and Injuries, Acute Coagulopathy, Tranexamic Acid, Emergency Medical Services
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.
Interventions
DRUGTranexamic 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.
DRUGPlacebo
Sponsors
National Health and Medical Research Council, Australia
Health Research Council, New Zealand
Monash University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| Coagulation assessed using the international normalised ratio (INR) | Immediately upon patient arrival to hospital |
| Units of blood products used (red blood cells, plasma, platelets, prothrombin complex concentrate, fibrinogen, Factor VIIa, cryoprecipitate) | 24 hours |
| Coagulation assessed by activated partial thromboplastin time (APTT) | Immediately upon patient arrival to hospital |
| Platelet count | Immediately upon patient arrival to hospital |
| 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 |
| Proportion of deaths due to bleeding, vascular occlusion (pulmonary embolus, stroke, acute myocardial infarction), multi-organ failure, or head injury | 24 hours |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Laboratory analysis of plasmin/anti-plasmin complexes | At the end of 8 hour infusion of study drug | — |
| Laboratory analysis of tissue type plasminogen activator (tPA) | At the end of 8 hour infusion 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 t-PA/PAI-1 complexes | At the end of 8 hour infusion of study drug | Substudy |
| Laboratory analysis of thrombin activatable fibrinolysis inhibitor (TAFI) | At the end of 8 hour infusion of study drug | Substudy |
| Laboratory analysis of interleukins (IL-2, IL-4, IL-6, IL-8, IL-10) | At the end of 8 hour infusion of study drug | Substudy |
| Laboratory analysis of granulocyte macrophage colony-stimulating factor (GM-CSF) | At the end of 8 hour infusion of study drug | Substudy |
| Laboratory analysis of interferon gamma | At the end of 8 hour infusion of study drug | Substudy |
| Laboratory analysis of tumour necrosis factor alpha | At the end of 8 hour infusion of study drug | Substudy |
| TXA concentration in blood | 8 hours after first dose of study drug | substudy |
| Laboratory analysis of fibrinolytic activity | At the end of 8 hour infusion of study drug | — |
| Blood lactate concentration | Immediately upon patient arrival to hospital | — |
Countries
Australia, New Zealand
Outcome results
None listed