Fibrinogen in the Initial Resuscitation of Severe Trauma (FiiRST) (FiiRST)
|ClinicalTrials.gov Identifier: NCT02203968|
Recruitment Status : Completed
First Posted : July 30, 2014
Last Update Posted : April 14, 2016
Trauma is the leading cause of death in people 44 years of age or younger. After major trauma, such as following high-speed motor vehicle collision, bleeding coupled with clotting defects is responsible for most of deaths in the first hours of hospital admission. Of note, these bleeding-related deaths are potentially preventable. Accordingly, the initial in-hospital management of severely injured patients focuses on stopping bleeding, replacing blood loss and correcting clotting defects.
Recently, animal and human research demonstrated that one of the major clotting defects following injury and bleeding is the drop in blood levels of fibrinogen (a clotting factor), which is detected on hospital admission in severely injured patients. These low fibrinogen levels are associated with increased blood transfusion and death. However, in North America, the standard of care for replacing low fibrinogen requires the use of cryoprecipitate, which is a frozen blood product with long preparation time, and similarly to other blood products, carries the risk of viral transmission and transfusion complications. Alternately, many Europeans countries where cryoprecipitate has been withdrawn from the market due to safety concerns, use fibrinogen concentrate. Fibrinogen concentrate undergoes pathogen inactivation, which is a process to eliminate the risk of transmitting viruses, bacteria and parasites, is likely a safer and faster alternative to cryoprecipitate. In Canada, fibrinogen concentrate is licensed for congenital low fibrinogen only.
Although preliminary data suggest that fibrinogen supplementation in trauma is associated with reduced bleeding, blood transfusion, and death, the feasibility, safety and efficacy of early fibrinogen replacement remains unknown. We proposed to conduct a feasibility randomized trial to evaluate the use of early fibrinogen concentrate against placebo in injured patients at our trauma centre.
A pilot trial is necessary to demonstrate the feasibility of rapidly preparing, delivering, and infusing fibrinogen concentrate as an early therapy to prevent excessive bleeding in trauma. This feasibility trial will provide preliminary safety and clinical outcome data to inform the design of larger trials; which ultimately aims to prevent bleeding-related deaths in the trauma population.
|Condition or disease||Intervention/treatment||Phase|
|Trauma Injury Bleeding Haemorrhage Coagulopathy||Drug: Fibrinogen concentrate Drug: Placebo Comparator||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||50 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Fibrinogen in the Initial Resuscitation of Severe Trauma (FiiRST): a Randomized Feasibility Trial|
|Study Start Date :||October 2014|
|Actual Primary Completion Date :||December 2015|
|Actual Study Completion Date :||December 2015|
Placebo Comparator: Normal saline
Placebo (normal saline) will be administered intravenously as a single 300ml rapid infusion (less than 3min) via level I automated pressure pump within one hour of hospital admission.
Drug: Placebo Comparator
Placebo Comparator: Normal saline Placebo (normal saline) will be administered intravenously as a single 300ml rapid infusion (less than 3min) via level I automated pressure pump within one hour of hospital admission.
Other Name: Normal saline
Active Comparator: Fibrinogen concentrate
Fibrinogen concentrate (RiaSTAP™) is a freeze-dried lyophilised plasma product presented in powdered form. The powder is reconstituted with water for intravenous injection at a concentration of 20 mg fibrinogen per ml. The concentrate is formulated with human albumin, L-arginine, sodium citrate and sodium chloride. RiaSTAP™ is supplied as a purified lyophilisate in a 1g dosage form and is reconstituted in 50 ml of sterile water. The final volume of RiaSTAP™ to be infused in this study will therefore be 300 ml.
Drug: Fibrinogen concentrate
Six grams of fibrinogen concentrate (RiaSTAP™) will be administered intravenously as a single 300ml rapid infusion (less than 3min) via level I automated pressure pump within one hour of hospital admission.
Other Name: RiaSTAP™
- Feasibility [ Time Frame: One year ]1.Feasibility endpoint: 1.1Proportion of patients receiving study intervention (Fibrinogen Concentrate [FC] or placebo) within first hour of hospital admission. Based on the trial's sample size of 50 patients, feasibility is defined by 85% (96% confidence interval (CI) [72% - 98%]) of study participants receiving the study intervention within the first hour of hospital admission
- Other feasibility endpoints and physiologic endpoints [ Time Frame: one year ]
Other feasibility endpoints:1.2.Proportion of patients receiving study intervention prior to any blood transfusion; 1.3.Times to randomization, issue, and start of infusion; 1.4.Duration of infusion; 1.5.Wastage of study intervention; 1.6.Proportion of patients with blood tests performed for all time points; 1.7.Proportion of missed patients (eligible but not randomized); 1.8.Randomization errors.
Physiologic endpoints: Plasma fibrinogen levels; Rotational Thromboelastometry/ Thromboelastography parameters (functional fibrinogen, fibtem, fibtem plus); plasmin anti-plasmin complex; tissue plasminogen activator; plasminogen activator inhibitor-1; d-dimer levels; international normalized ratio [INR]; partial thromboplastin time; complete blood count; endogenous thrombin potential; factor XIII; factor V; and activated protein C will be obtained on admission; and +1h, +3h, +11h, +23h & +47h following start time of study infusion
- Clinical Parameters [ Time Frame: one year ]
Rates of symptomatic thromboembolic complications in both study arms defined by the evidence of any of the following any time during hospital stay: deep venous thrombosis; myocardium infarction; cerebral vascular accident; pulmonary embolism; and arterial thrombosis
Rates of asymptomatic deep venous thrombosis by leg doppler at day 7 of hospital stay
Mortality by exsanguination
All-cause mortality at 28 days (mainly due to exsanguination; mainly neurological/ due to traumatic brain injury/ withdrawal of care; or mainly due to multiple organ failure/sepsis)
Incidence of acute lung injury/ acute respiratory distress syndrome before day 28
Multiple organ failure
Total amount of crystalloids used in 24h
Units of blood and blood products transfused in 24h of hospitalization
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02203968
|Sunnybrook Health Sciences Centre|
|Toronto, Ontario, Canada, M4N3M5|
|Principal Investigator:||Barto Nascimento, MD MSc||Sunnybrook Health Sciences Centre, University of Toronto|