Fibrinogen Early In Severe Trauma studY (FEISTY): study protocol for a randomised controlled trial

Abstract

BackgroundHaemorrhage is a leading cause of death in severe trauma. Fibrinogen plays a critical role in maintaining haemostasis in traumatic haemorrhage. Early fibrinogen replacement is recommended by several international trauma guidelines using either fibrinogen concentrate (FC) or cryoprecipitate (Cryo). There is limited evidence to support one product over the other with widespread geographic and institutional variation in practice. This pilot trial is the first randomised controlled trial comparing FC to Cryo in traumatic haemorrhage.Methods/designThe Fibrinogen Early In Severe Trauma studY (FEISTY) is an exploratory, multicentre, randomised controlled trial comparing FC to Cryo for fibrinogen supplementation in traumatic haemorrhage. This trial will utilise thromboelastometry (ROTEM®) to guide and dose fibrinogen supplementation. The trial will recruit 100 trauma patients at four major trauma centres in Australia. Adult trauma patients with evidence of haemorrhage will be enrolled on arrival in the trauma unit and randomised to receiving fibrinogen supplementation with either FC or Cryo. The primary outcome is the differential time to fibrinogen supplementation. There are a number of predetermined secondary outcomes including: effects of the intervention on plasma fibrinogen levels, feasibility assessments and clinical outcomes including transfusion requirements and mortality.DiscussionThe optimal method for replacing fibrinogen in traumatic haemorrhage is fiercely debated. In this trial the feasibility and efficacy of fibrinogen supplementation using FC will be compared to Cryo. The results of this pilot study will facilitate the design of a larger trial with sufficient power to address patient-centred outcomes.Trial registrationClinicalTrials.gov, ID: NCT02745041. Registered 4 May 2016.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-1980-x) contains supplementary material, which is available to authorized users.

Hemostatic profile and safety of pooled cryoprecipitate up to 120 hours after thawing

“…Compared to cryoprecipitate, however, lyophilized fibrinogen concentrate is very expensive and lacks other coagulation factors (FVIII, vWF, and FXIII). A clinical trial comparing the feasibility and efficacy of fibrinogen concentrate and cryoprecipitate to replace fibrinogen early in severe trauma is ongoing …”

Defining trauma‐induced coagulopathy with respect to future implications for patient management: Communication from the SSC of the ISTH

“…A large observational study in combat‐injured patients in Afghanistan suggested that supplementation with cryoprecipitate may have independent survival benefit . Current European guidelines suggest the early empiric administration of higher concentrations of fibrinogen, although the benefits are currently being assessed in a number of clinical trials …”

“…46 Current European guidelines suggest the early empiric administration of higher concentrations of fibrinogen, 47 although the benefits are currently being assessed in a number of clinical trials. 48 Acute severe injury and haemorrhagic shock cause a complex response of the innate immune and inflammatory systems that are tightly coupled with the coagulation system. 49 Damageassociated molecular pattern proteins (DAMPs) released during tissue injury 50,51 and ischemia/reperfusion 52-54 elicit time-dependent changes in coagulation and fibrinolysis that may have common pathways; namely, immediate thrombin generation, t-PA availability, and later suppression of fibrinolysis by PAI-1.…”

Viscoelastic haemostatic assays and fibrinogen in paediatric acute traumatic coagulopathy: A comprehensive review

“…While there is no evidence proving a difference in efficacy between cryoprecipitate and FC, there are practical factors that may allow more rapid administration in clinical practice. A number of studies have investigated the time to administration of fibrinogen replacement and have compared FC to cryoprecipitate but as yet there have been no large studies powered for patient‐centred outcomes or reduction in blood product usage . Systems that achieve early and rapid fibrinogen replacement generally involve empiric delivery of FC to patients presenting with clinical indications of severe bleeding, not those exclusively with a low fibrinogen level .…”

“…A number of studies have investigated the time to administration of fibrinogen replacement and have compared FC to cryoprecipitate but as yet there have been no large studies powered for patient-centred outcomes or reduction in blood product usage. 51,54,55 Systems that achieve early and rapid fibrinogen replacement generally involve empiric delivery of FC to patients presenting with clinical indications of severe bleeding, not those exclusively with a low fibrinogen level. 56,57 Empiric, immediate transfusion therapy such as the early coagulation support protocol, which provides FC to patients meeting clinical parameters on presentation and before ROTEM or SLT results, have been able to reduce the administration time to under 30 min.…”