Efficacy and Safety of Early Use PCC in Severe Trauma (eFAST)

Evaluation of the Efficacy and Safety of Early Use of a Four-factor Prothrombin Complex Concentrates in Patients With Severe Traumatic Hemorrhage: a Multicenter, Randomized Controlled, Open-label Clinical Study

Uncontrolled hemorrhage within 24 hours after severe trauma is the main cause of death in trauma patients. Hemorrhagic shock may be accompanied by traumatic coagulopathy in the early stages of severe trauma. Among them, the main pathogenesis of traumatic coagulation disorder is tissue injury, hypoperfusion, inflammatory response and , increased consumption of coagulation factor, loss of coagulation factor caused by massive bleeding, low temperature and other factors aggravate the disorder of coagulation function and cause hyperfibrinolysis. Studies have shown that the fatality rate of patients with severe traumatic coagulopathy is 4-8 times higher than that of patients without coagulopathy. Active and effective injury-controlled resuscitation and surgical treatment, target-oriented supplementation of coagulation substrate and correction of coagulation function are the main measures for high-quality treatment of patients with severe trauma. Therefore, early improvement of coagulation function is the key to improve the comprehensive treatment level of patients with severe trauma.

At present, four-factor prothrombin complex (4F-PCC) is a compound preparation containing coagulation factors Ⅱ, VII, IX and X separated from fresh plasma of healthy people. However, large-scale, long-term observation of the efficacy and safety of the early application of 4F-PCC in traumatic massive hemorrhage has not been proven.

In this study, it is to study the efficacy and safety of early use of 4F-PCC in patients with severe traumatic massive hemorrhage through a multi-center, randomized controlled and open-label clinical trial.

Study Overview

• Status: Completed
• Conditions: Severe Trauma; Traumatic Shock
• Intervention / Treatment: Drug: 4 factor Prothrombin Complex Concentrates

Detailed Description

The treatment of severe traumatic hemorrhage, hemorrhagic shock and traumatic coagulopathy includes timely correction of massive hemorrhage, timely use of proportional transfusion of blood products to ensure effective fluid volume resuscitation and temperature maintenance, and achieve target-oriented correction of coagulopathy while taking into account thrombosis prevention and other comprehensive therapeutic strategies. Therefore, more and more European and American countries begin to apply Coagulation Factor Concentrates (Coagulation Factor Concentrates, CFCs) included Prothrombin Complex Concentrates (PCC) and Fibrinogen Concentrates (FC) for early resuscitation and target-directed coagulation management. Compared with FFP alone, the advantages of CFCs to correct coagulation dysfunction include: by providing standardized and high concentration of coagulation factors, reducing virus transmission and transfusion-related adverse reactions (such as acute respiratory distress syndrome, sepsis and multiple organ failure), immediate use without matching, and easy operation; The bolus use of PCC can effectively reduce the need for blood transfusion, achieve faster correction of coagulation function and reduce in-hospital mortality. A prospective, single-center, randomized controlled trial found that early use of fibrinogen concentrate (FC) may reduce blood transfusion volume and the incidence of multiple organ failure . However, at present, for patients with severe trauma and massive hemorrhage, the use of MTP and blood products can only be effectively implemented on the basis of the completion of coagulation function test, accurate thrombus elastogram (TEG) and dynamic evaluation of the body's coagulation function. However, the acquisition of TEG test results is often slow, which cannot timely and effectively guide clinicians to carry out target-oriented use of blood products and clinical mass transfusion in early stage. In addition, when hemorrhagic shock cannot be effectively corrected in patients with severe traumatic massive hemorrhage in the early stage, timely treatment of coagulopathy is delayed. In conclusion, timely and sufficient supplement of prothrombin complex PCC and other blood products may have certain application value for timely and effective correction of coagulation dysfunction.

Prothrombin complex (PCC) is a kind of plasma protein concentrate containing coagulation factor which is isolated and prepared from healthy human mixed plasma. However, the efficacy and safety of 4F-PCC in early dosing and bunching of traumatic massive bleeding have not been demonstrated by prospective multicenter randomized controlled trials. In addition to the application of PCC in patients with traumatic hemorrhage complicated by anticoagulant drugs, the European Guidelines for Massive Hemorrhage 2023 Edition lacks clear guidelines for the treatment of patients with severe traumatic hemorrhage complicated with coagulopathy. Pharmacovigilance data suggest that the risk of thromboembolic complications in PCC may be low, but the primary source of these data is vitamin K antagonist reversal . Therefore, for the application of PCC in the management of traumatic coagulopathy, there is still a lack of scientific clinical practice guidance basis, and systematic prospective research is needed at the same time.

Therefore, we can assume that early use of 4F-PCC in severe trauma with hemorrhagic shock can correct bleeding and coagulodysfunction as soon as possible, thereby preventing circulatory, respiratory and renal multiple organ failure and improving prognosis. In addition, the lack of blood products and the difficulty in the implementation of massive blood transfusion plan also put forward a higher demand for the early and efficient use of clotting substrates in the treatment of patients with massive traumatic hemorrhage. This has also become an important research content in this study, such as the early empirical use of 4-PCC to improve the clinical prognosis of patients with severe traumatic massive hemorrhage, reduce the need for blood products, quickly correct coagulation dysfunction, and reduce the risk of thrombosis events. Therefore, this study intends to conduct early empirical bunching of 4-PCC in patients with severe traumatic massive hemorrhage, and evaluate its effectiveness and safety in the early stage of severe traumatic massive hemorrhage through a multicenter, randomized controlled, open-label study. To further improve the treatment of traumatic massive hemorrhage to provide a certain reference basis; It also provides the theoretical basis and clinical practice for correcting coagulation dysfunction in the early stage of severe trauma treatment.

• Study Type: Interventional
• Enrollment (Actual): 380
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Yongan Xu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years, or < 80 years
• Grade of triage: 1-2
• <3 hours after injury
• Assessment of blood consumption(ABC) score ≥2; Or an estimated infusion of 3 units of concentrated red blood cells within 1 hour after admission; or 10 units of concentrated red blood cells within 24 hours after admission
• Obtain the informed consent of the patient

Exclusion criteria :

• PCC was used before admission
• Taking anticoagulant drugs (such as low molecular weight heparin, rivaroxaban, warfarin, etc.)
• History of deep vein thrombosis (VTE, pulmonary embolism (PE) and myocardial infarction History of coronary stent within 6 months
• Patients who suffered cardiac arrest upon admission and before enrollment
• Have a history of heparin allergy or heparin-induced thrombocytopenia
• Allergic to PCC
• Women who are lactating, pregnant, or pregnant
• Patients with various mental illnesses lose their capacity for civil conduct
• Hemophilia A and other blood system diseases, severe liver disease, cirrhosis and other blood coagulation
• No capacity for civil right

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment of prothrombin complex concentrate; Based on the treatment plan of the control group, a single frequency of intravenous infusion of 4F-PCC was added. Therapeutic dose: 25 IU/kg. Infusion time: starting within 2 hours after admission Infusion method: Each bottle of 4F-PCC should be injected with a sterile solution pre-warmed to 20~30℃. Dilute with water to 25ML solution, then use a filter with the required amount of solution. The infusion is completed within 60 minutes. Basic treatment according to "The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition".	Drug: 4 factor Prothrombin Complex Concentrates; Based on the treatment plan of the control group, a single frequency of intravenous infusion of 4F-PCC (Boya) was added. Therapeutic dose: 25 IU/kg (rich in FVII, IX, II, and X) Infusion time: infusion as soon as possible, starting within 2 hours after admission at the latest Infusion method: Each bottle of 4F-PCC should be injected with a sterile solution pre-warmed to 20~30℃. Dilute with water to 25ML solution, then use a filter with the required amount of solution The device's blood transfusion device performs intravenous infusion, and the infusion is completed within 60 minutes.
No Intervention: control group by Basic treatment; Basic treatment according to "The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition".

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of multiple organ failure within 7 days	Incidence of multiple organ failure within 7 days after enrollment	within 7 days after enrollment
Day 28-mortality	the mortality within Day 28 after enrollment	within Day 28 after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The total volume of blood products within 24 hours after trauma	The total volume of blood products (red blood cells, fresh frozen plasma,platelets) within 24 hours after trauma	within 24 hours after admission
The total volume of blood products within Day 3 after trauma	The total volume of blood products (red blood cells, fresh frozen plasma, platelets) within Day 3 after trauma	within Day 3 after admission
The total volume of coagulation substrate within Day 1 after trauma	The total volume of coagulation substrate (fibrinogen, cryoprecipitate,tranexamic acid) within Day1 after trauma	within Day 1 after admission
The total volume of coagulation substrate within Day 3 after trauma	The total volume of coagulation substrate (fibrinogen, cryoprecipitate,tranexamic acid) within Day 3 after trauma	within Day 3 after admission
Incidence of thrombotic events at early stage	incidence of VTE(including deep vein thrombosis ,DVT), pulmonary embolism (PE),etc.）	DAY 2 after admission
Incidence of thrombotic events at early stage	incidence of cerebrovascular embolism, myocardial ischemia, and mesenteric arterial and venous thrombosis, etc.	Day 2 after admission
Incidence of thrombotic events at late stage (Day2 to Day 7)	incidence of VTE or PE	from Day2 to Day 7 after admission
ICU mortality	ICU mortality	within Day 28 after admission
overall mortality	overall mortality during Day 28 after enrollment	within Day 28 after admission
Length of mechanical ventilation within Day 28 after trauma	Days of mechanical ventilation and free days Without ventilation after admission	within Day 28 after admission
length of stay in ICU during 28 days after trauma	length of stay in ICU	within 28 days after admission
length of stay in hospital within 28 days after trauma	length of stay in hospital	within 28 days after admission
Coagulation profile at 12-Hour after enrollment	Coagulation profile (PT, APTT, INR, fibrinogen) within 12 hours after enrollment	within 12 hours after enrollment
Coagulation profile at Day 1 after enrollment	Coagulation profile (PT, APTT, INR, fibrinogen) within Day1 after enrollment	within Day 1 after enrollment
Coagulation profile at Day 3 after enrollment	Coagulation profile (PT, APTT, INR, fibrinogen) at Day 3 after enrollment	within Day 3 after enrollment
TEG at Hour 12 after enrollment	TEG at Hour 12 after enrollment	within Hours12 after enrollment
TEG at Day1 after enrollment	TEG at Day1 after enrollment	at Day1 after enrollment
TEG at Day 3 after enrollment	TEG at Day 3 after enrollment	Day 3 after enrollment

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Ningbo Medical Center Lihuili Hospital; Second Affiliated Hospital of Wenzhou Medical University; Jinhua Municipal Central Hospital; The People's Hospital of Quzhou; Shaoxing People's Hospital; Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University; Ningbo No.2 Hospital; Lishui Country People's Hospital; The Third Affiliated Hospital of Wenzhou Medical University; Affiliated Hospital of Jiaxing University
• Investigators: Study Chair: yongan xu, doctor, Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2023
• Primary Completion (Actual): June 30, 2025
• Study Completion (Actual): June 30, 2025

Study Registration Dates

• First Submitted: February 13, 2023
• First Submitted That Met QC Criteria: February 21, 2023
• First Posted (Actual): February 22, 2023

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: trauma; injury; Hemorrhagic shock
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Shock; Pathological Conditions, Signs and Symptoms; Wounds and Injuries; Shock, Hemorrhagic; Shock, Traumatic; Hemostatics; Coagulants; Thrombin
• Other Study ID Numbers: 2023-0029

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