Early Administration of Fibrinogen in Polytraumatized Patients With Hypofibrinogenemia: a Randomized Feasibility Trial

Study Overview
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Brief Summary
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This is a randomized feasibility trial conducted with severe trauma patients. At admission patients presented hypofibrinogenemia, hypotension and tachycardia. The primary outcome was feasibility assessed by the proportion of patients receiving the allocated treatment up to 60 minutes after randomization. The treatments regards to receive or not to receive an early replacement of fibrinogen.

Detailed Description
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This is a randomized feasibility trial conducted between December 2015 and January 2017 with severe trauma patients (Index of Shock Severity [ISS] ≥ 15) admitted to the emergency room of a large trauma center. At admission patients presented qualitative hypofibrinogenemia (FIBTEM A5 ≤ 9 mm), hypotension (systolic blood pressure <90 mmHg) and tachycardia (heart rate > 100 bpm). The primary outcome was feasibility assessed by the proportion of patients receiving the allocated treatment up to 60 minutes after randomization meaning receive replacement through fibrinogen concentrate (50mg per kg of body weight) by the intervention group and not to receive an early replacement of fibrinogen by control group.

Official Title
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Early Administration of Fibrinogen Concentrate in Polytraumatized Patients With Thromboelastometry Suggestive of Hypofibrinogenemia: a Randomized Feasibility Trial

Conditions
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Trauma, Bleeding Disorder, Fibrinogen; Deficiency, Acquired

Intervention / Treatment
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* Drug: Fibrinogen concentrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 80 years Severe trauma patients (Index of Shock Severity [ISS] ≥ 15) Hypotension (systolic blood pressure < 90 mmHg) Tachycardia (heart rate > 100 bpm) Qualitative hypofibrinogenemia (FIBTEM A5 ≤ 9 mm) Exclusion Criteria: Patient or family do not agree to sign the informed consent form Eligible for institutional massive transfusion protocol Pregnant Previous coagulopathy disorders Use of anticoagulants drugs and/or platelet anti aggregation drugs (exception for aspirin) Previous thromboembolic disorders or events Cardiopulmonary arrest before hospital admission Patient admitted after another hospital transfer Time from trauma to screening above six hours Patients with exclusively traumatic brain injury

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Not to receive an early replacement of fibrinogen | |
| Experimental: Intervention<br>Receive early replacement through fibrinogen concentrate (50mg per kg of body weight) | Drug: Fibrinogen concentrate<br>* Receive fibrinogen concentrate 50mg/kg of body weight after randomization<br>* Other names: Haemocomplettan®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility assessed by the proportion of patients receiving the allocated treatment up to 60 minutes after randomization | The proportion of patients receiving the allocated treatment up to 60 minutes after randomization | 60 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall blood tube drainage | Overall blood tube drainage | 48 hours | 
| Overall blood tube drainage | Overall blood tube drainage | Up to four weeks - Through the length of hospital stay | 
| Transfusion requirements assessed as units of red blood cell, fresh frozen plasma, blood platelets and cryoprecipitate | Transfusion requirements | 48 hours | 
| Transfusion requirements assessed as units of red blood cell, fresh frozen plasma, blood platelets and cryoprecipitate | Transfusion requirements | Up to four days - Through the Length of operating room stay | 
| Transfusion requirements assessed as units of red blood cell, fresh frozen plasma, blood platelets and cryoprecipitate | Transfusion requirements | Up to four weeks - Through the Length of intensive care unit stay | 
| Transfusion requirements assessed as units of red blood cell, fresh frozen plasma, blood platelets and cryoprecipitate | Transfusion requirements | Up to four weeks - Through the Length of operating room stay | 
| Costs of blood therapy assessed by de median value spent on each patient due to red blood cell, fresh frozen plasma, blood platelets, cryoprecipitate and fibrinogen concentrate | Costs of blood therapy | Up to four weeks - Through the Length of operating room stay | 
| Thromboembolic events assessed by any clinical manifestation that can be related to a thromboembolic event | Thromboembolic events | First two weeks after hospital admission | 
| Reoperate due to bleeding | Reoperate due to bleeding | Up to four weeks - Through the Length of operating room stay | 
| Ventilator-free days | Ventilator-free days | Up to four weeks - Through the Length of operating room stay | 
| Vasopressor-free days | Vasopressor-free days | Up to four weeks - Through the Length of operating room stay | 
| Length of hospital stay | Length of hospital stay | Up to four weeks - Through the Length of operating room stay | 
| Length of intensive care unit stay | Length of intensive care unit stay | Up to four weeks - Through the Length of intensive care unit stay | 
| In-hospital Deaths | In-hospital Deaths | Up to four weeks - Through the Length of operating room stay | 
| Sequential Organ Failure Assessment (SOFA) score on the first day after intensive care unit admission | The Sequential Organ Failure Assessment (SOFA) score is a mortality prediction score that is based on the degree of dysfunction of 6 organ systems. The SOFA score can be used to determine the level of organ dysfunction and the mortality risk in ICU patients. High values means worst outcomes | First day after intensive care unit admission | 
| Sequential Organ Failure Assessment (SOFA) score on the fifth day after intensive care unit admission | The Sequential Organ Failure Assessment (SOFA) score is a mortality prediction score that is based on the degree of dysfunction of 6 organ systems. The SOFA score can be used to determine the level of organ dysfunction and the mortality risk in ICU patients. High values means worst outcomes | Fifth day after intensive care unit admission | 
| Sequential Organ Failure Assessment (SOFA) score on the seventh day after intensive care unit admission | The Sequential Organ Failure Assessment (SOFA) score is a mortality prediction score that is based on the degree of dysfunction of 6 organ systems. The SOFA score can be used to determine the level of organ dysfunction and the mortality risk in ICU patients. High values means worst outcomes | Seventh day after intensive care unit admission | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trauma, Coagulopathy, Fibrinogen, Fibrinogen Concentrate, Thromboelastometry, Hypofibrinogenemia, Early Fibrinogen Replacement