Fibrinogen Early In Severe Trauma studY II (FEISTY II): study protocol for a randomised clinical trial of fibrinogen concentrate vs cryoprecipitate in traumatic haemorrhage in Australia and New Zealand

Abstract

Haemorrhage is a leading cause of preventable death amongst severe trauma patients and is often complicated by hypofibrinogenaemia. Fibrinogen replacement can be achieved using fibrinogen concentrate (FC) or Cryoprecipitate (Cryo), but comparative evidence in traumatic haemorrhage is limited. To determine, in trauma patients with major haemorrhage and hypofibrinogenaemia, whether fibrinogen replacement using FC compared to Cryo increases the number of days alive and out of hospital (at home) within the first 90 days after randomisation (DAOH 90 ). The Fibrinogen Early In Severe Trauma studY II (FEISTY II) is a phase III, multi-centre, randomised, two-arm parallel, open-label, superiority trial comparing FC and Cryo for fibrinogen replacement in severely injured trauma patients with major haemorrhage and hypofibrinogenaemia. Inclusion criteria are adults (≥ 18 years) affected by trauma and judged to have significant active haemorrhage with FIBTEM A5 ≤ 10 mm, TEG FF A10 ≤ 15 mm or FibC ≤ 2 g/L, for whom the local Major Haemorrhage Protocol (MHP) has been activated and/or emergency blood products have been transfused. Exclusion criteria are injuries judged incompatible with survival, inability to randomise within 6 h of trauma centre admission, pregnancy, objection to blood products, genetic or acquired coagulation disorder, dedicated fibrinogen replacement prior to randomisation, participation in competing study, and pre-existing co-morbidity that may interfere with the assessment of outcome. Patients will be block randomised 1:1 and stratified by site and clinical suspicion of Traumatic Brain Injury. The primary outcome is DAOH 90 . Secondary outcomes include all-cause mortality, transfusion requirements and measures of functional recovery and quality of life. Safety data will include symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE), myocardial infarction (MI), ischaemic stroke and transfusion reactions. A total of 900 patients will be recruited by trauma centre clinical staff across 23 trauma centres in Australia and New Zealand. The optimal approach to fibrinogen replacement in traumatic haemorrhage remains uncertain. FEISTY II is a multi-centre randomised clinical trial in severely injured bleeding trauma patients, comparing FC to Cryo in terms of efficacy, safety, and cost-effectiveness. ClinicalTrials.gov. NCT05449834 . Registered on 08 July 2022. 1st Participant enrolled 21 November 2022.