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

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

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.

Study Overview

• Status: Completed
• Conditions: Trauma; Bleeding Disorder; Fibrinogen; Deficiency, Acquired
• Intervention / Treatment: Drug: Fibrinogen concentrate

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 05403-000
    • Hospital das Clinicas - FMUSP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Investigators: Principal Investigator: Lucas S Lucena, MD, Hospital das Clínicas da FMUSP

Publications and helpful links

General Publications

• Lucena LS, Rodrigues RDR, Carmona MJC, Noronha FJD, Oliveira HP, Lima NM, Pinheiro RB, Silva WAD, Cavalcanti AB. Early administration of fibrinogen concentrate in patients with polytrauma with thromboelastometry suggestive of hypofibrinogenemia: A randomized feasibility trial. Clinics (Sao Paulo). 2021 Nov 8;76:e3168. doi: 10.6061/clinics/2021/e3168. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): July 1, 2018

Study Registration Dates

• First Submitted: August 9, 2016
• First Submitted That Met QC Criteria: August 9, 2016
• First Posted (Estimate): August 12, 2016

Study Record Updates

• Last Update Posted (Actual): August 1, 2018
• Last Update Submitted That Met QC Criteria: July 31, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Trauma; Fibrinogen; Thromboelastometry; Coagulopathy; Fibrinogen Concentrate; Hypofibrinogenemia; Early Fibrinogen Replacement
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Blood Coagulation Disorders
• Other Study ID Numbers: 662.182

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No