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

• Applicant: Professor Dr. Marc Maegele
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 400971975

Uncontrolled hemorrhage and acute traumatic coagulopathy (ATC) are the major causes for preventable death after trauma. ATC occurs immediately after injury with activation of inflammatory/coagulation cascades, including clot break down (fibrinolysis). Registries confirmed a high frequency of ATC in trauma patients with 1/3 displaying laboratory coagulopathy including fibrinolysis on hospital admission. Despite methodological deficits the early use of TXA was adopted by many clinical algorithms/guidelines to guide therapies in ATC based upon the results of the recent randomized-controlled CRASH-2 trial. Important aspects with the use of TXA in bleeding trauma patients with ATC, in particular with respect to dosing, timing and mechanism by which TXA works in this setting remain scarce. While CRASH-2 found all-cause mortality was reduced in adult trauma patients with, or at risk of, significant haemorrhage a post-hoc analysis also found an unexpected and yet unexplained increase in death due to bleeding when TXA was given beyond 3 hours from injury. Almost all patients in CRASH-2 were treated in low/middle-income countries with different standards for the management of ATC/trauma, higher baseline mortality, and a younger patient population than most trauma centres in high-income countries. Meanwhile, there is an increasing number of studies conducted in advanced trauma systems which could not replicate the results from CRASH-2; indeed, these studies report increasing frequencies of side-effects including thromboembolic events and also mortality and call for a more selective use of TXA in bleeding trauma patients. We will conduct a multi-centre randomized placebo-controlled trial to assess the overall benefits and harms of early pre-hospital TXA administration for severely injured patients at high risk of ATC who are treated in advanced trauma systems with rapid access to blood products, surgery, angioembolisation, and critical care and whether it improves survival and recovery at 6 months. It may be that, in advanced settings, TXA combined with other treatments to minimise bleeding and support clotting, especially in patients with age-related comorbidities and medications, might lead to harmful pro-thrombotic events that outweigh any benefits. The study has been initiated in Australia/New Zealand through the ANZICS-CTG and be extended to air rescue centres (HEMS) with affiliated trauma centres in Germany.

• DFG Programme: Clinical Trials