TraumaPhase 1/2FiiRSTNCT02203968
Fibrinogen in the Initial Resuscitation of Severe Trauma (FiiRST)
A Phase 1/2 study testing Fibrinogen concentrate in people with Trauma and Injury, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Fibrinogen concentrate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteCanada
- Study dates
- Oct 2014to Dec 2015
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Injured trauma (penetrating or blunt) patients who are at risk of significant bleeding, defined as: i. Systolic blood pressure (SBP) ≤ 100mmHg at any time from the injury scene until 30min after hospital admission AND ii. Red blood cell transfusion has been ordered by the trauma team leader (or delegate)
Who cannot join
- Patients in shock which the etiology is purely not related to bleeding:
- Cardiogenic (myocardial or valvular dysfunction); ii. Distributive (septic, anaphylactic, acute adrenal insufficiency and neurogenic) and iii. Obstructive (cardiac tamponade, tension pneumothorax and massive pulmonary emboli).
- Severe head injury, defined as any of the following:
- Glasgow coma scale (GCS) of 3 due to severe traumatic brain injury (TBI); ii. TBI with clear indication of immediate neurosurgical intervention based on clinical findings (mechanism of trauma associated with focal signs such as anisocoria with fixed pupil) or on CT results (bleeding causing mass effect); iii. Unsalvageable head injury such as through-through gunshot wound to the head, open skull fracture with exposure/loss of brain tissue; as per the trauma team or neurosurgery initial clinical assessment or as per initial CT of the head findings;
- Known complete or incomplete spinal cord injury;
- Known hereditary or acquired coagulopathies unrelated to the trauma resuscitation (e.g. known hepatic dysfunction);
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- Use of anticoagulant medications such as warfarin, low-molecular weight heparin, and direct thrombin and factor Xa inhibitors;
- Moribund with evidence of unsalvageable injuries and withdrawal of care, as per the trauma team;
- Received blood products prior to admission;
- Patients with estimated body weight under 50Kg;
- Patients with known or suspected pregnancy;
- Patients arriving more than 6hr after injury.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Fibrinogen in the Initial Resuscitation of Severe Trauma (FiiRST): a Randomized Feasibility Trial
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.
Read more
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.
- Conditions
- Trauma, Injury, Bleeding, Haemorrhage, Coagulopathy
- Being tested
- Fibrinogen concentrate, Placebo Comparator
- Keywords
- Fibrinogen replacement, Trauma coagulopathy, Hypofibrinogenemia, Early trauma coagulopathy, Haemorrhage, Fibrinogen concentrate, Feasibility trial, Clinical trials
- Medical subject headings
- Wounds and Injuries, Hemorrhage, Hemostatic Disorders, Afibrinogenemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fibrinogen concentrateDrug
Also called RiaSTAP™
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.
Placebo ComparatorDrug
Also called Normal saline
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.
| Study group | Role | What they receive |
|---|---|---|
| Normal saline | Placebo comparator | 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. Receives: Drug: Placebo Comparator |
| Fibrinogen concentrate | Active comparator | 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. Receives: Drug: Fibrinogen concentrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility
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
Measured: One year
Secondary outcomes (1)
Other feasibility endpoints and physiologic endpoints
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
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2014 (estimated)
- Study startOct 2014
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TraumaStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Barto Nascimento, MD MSc, Principal investigator, Sunnybrook Health Sciences Centre, University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02203968
- Sponsor's protocol ID
- 064-2014
- Acronym
- FiiRST
- Status last verified
- Apr 2016
- First submitted
- 8 Jul 2014
- Last updated
- 14 Apr 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fibrinogen in the Initial Resuscitation of Severe Trauma (FiiRST): a Randomized Feasibility Trial
- ClinicalTrials.gov ID
- NCT02203968
- Acronym / sponsor ID
- FiiRST / 064-2014
- Conditions
- Trauma, Injury, Bleeding, Haemorrhage, Coagulopathy
- Keywords
- Fibrinogen replacement, Trauma coagulopathy, Hypofibrinogenemia, Early trauma coagulopathy, Haemorrhage, Fibrinogen concentrate, Feasibility trial, Clinical trials
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- Oct 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 30 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Normal saline | Placebo comparator | Drug: Placebo ComparatorPlacebo (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. |
| Fibrinogen concentrate | Active comparator | Drug: Fibrinogen concentrateFibrinogen 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 1. Injured trauma (penetrating or blunt) patients who are at risk of significant bleeding, defined as: i. Systolic blood pressure (SBP) ≤ 100mmHg at any time from the injury scene until 30min after hospital admission AND ii. Red blood cell transfusion has been ordered by the trauma team leader (or delegate)
Key exclusion criteria (12 listed)
- Patients in shock which the etiology is purely not related to bleeding:
- Severe head injury, defined as any of the following:
- Known complete or incomplete spinal cord injury;
- Known hereditary or acquired coagulopathies unrelated to the trauma resuscitation (e.g. known hepatic dysfunction);
- Use of anticoagulant medications such as warfarin, low-molecular weight heparin, and direct thrombin and factor Xa inhibitors;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fibrinogen concentrateAlso: RiaSTAP™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. | Drug | Fibrinogen concentrate |
| Placebo ComparatorAlso: Normal salinePlacebo 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 | Normal saline |
Primary outcome
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
1 secondary outcome
Other feasibility endpoints and physiologic endpoints
Time frame: one year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Barto Nascimento, MD MSc principal investigator
Sunnybrook Health Sciences Centre, University of Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Fibrinogen concentrate in people with Trauma and Injury, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility (time frame: One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2016.