Early Administration of Prothrombin Concentrate Complex in Patients With Acute Hemorrhage Following Severe Trauma

Study Overview
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Brief Summary
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Acute traumatic coagulopathy (ATC) is common in severe trauma patients (around 25 to 30% of patients with severe trauma) and is associated with increased mortality. ATC is associated with fibrinogen and clotting factors deficiencies. Therefore, ATC management relies on early administration of fibrinogen and blood products in case of massive transfusion with a 1:1 or 1:2 ratio between Fresh Frozen Plasma (FFP) and Red Blood Cells (RBC). This strategy relies on fast supply of FFP. To overcome delay for FFP ordering, transport and defrosting, the PROCOAG study proposes to use prothrombrin concentrate complex (PCC) as alternative to treat coagulation factor deficiency. PCC is readily available upon hospital arrival. In addition to fibrinogen treatment, it is thought that PCC can be efficient in ATC management, while reducing risks associated with massive transfusion. ProCoag is a randomized, controlled, double-blinded, parallel clinical trial aiming at showing superiority of early PPC+ fibrinogen strategy on fibrinogen only strategy for the management of patients at risk of massive transfusion. Early administration of PPC should optimize patient blood management and therefore reduce blood products transfused within the first 24 hours following a severe trauma.

Official Title
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Impact of Early Administration of Prothrombin Concentrate Complex in Patients With Acute Hemorrhage Following Severe Trauma

Conditions
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Shock, Hemorrhagic

Intervention / Treatment
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* Drug: Pro-Thrombin Concentrate Complex
* Drug: NaCl 0.9%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Primary admission for a severe trauma Out-of-hospital transfusion or RBC transfusion within the first hour following hospital admission Clinical prediction or ABC score (Assessment of Blood Consumption) ≥ 2 of massive transfusion defined by a transfusion of at least 10 CGR during the first 24 hours or 3 CGR during the first hour. Informed consent signed by a relative or emergency procedure Exclusion Criteria: Cardiac arrest before randomisation Secondary transfer from another hospital (a technical stop is accepted) Post-traumatic lesions out of therapeutic resources with death expected in the hour following hospital admission Anti-coagulation treatment (K anti-vitamine, new oral anticoagulant) Pregnancy Hypersensitivity to active substances or one of the excipients of KANOKAD® Patient treated with an experimental medicine within the last 30 days Decision of therapeutic limitation before randomisation Patient protected by article L1121-7 of the French Public health code. Knowledge of a contraindication to the use of NaCl 0.9% at the dose of 1 mg/kg (hyperchloremia, hypernatremia...)

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PCC treatment<br>Conventional strategy for ATC management in addition to of intravenous Pro-Thrombin Concentrate Complex (25IU/kg factor IX) | Drug: Pro-Thrombin Concentrate Complex<br>* Patient at risk of massive hemorrhage will be managed with standard care with 1ml/kg PCC.<br>* Other names: KANOKAD;|
| Placebo Comparator: Placebo treatment<br>Conventional strategy for ATC management without PCC (NaCl 0.9%) | Drug: NaCl 0.9%<br>* Patient at risk of massive hemorrhage will be managed with standard care with 1ml/kg Saline solution.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Labile blood products transfused in the first 24 hours | This outcome is measured in number of bags administered | 24 hours following hospital admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RBC (Red Blood Cells) transfused in the first 24 hours | This outcome is measured in number of bags administered | 24 hours following hospital admission | 
| FFP transfused in the first 24 hours | This outcome is measured in number of bags administered | 24 hours following hospital admission | 
| Platelets transfused in the first 24 hours | This outcome is measured in number of bags administered | 24 hours following hospital admission | 
| Time to achieve Prothrombin ratio < 1.5 |  | Within the first 24 hours | 
| Time to hemostasis | Hemostasis is defined as bleeding control in the surgical field or resolution of contrast blush after embolization during interventional radiology | Within the first 24 hours following admission | 
| Thrombo-embolic events |  | ICU stay (an average of 28 days) | 
| Mortality |  | 24 hours and Day 28 | 
| ICU-free days | Number of in-hospital days outside Intensive Care Unit (ICU) | Hospital stay (an average of 28 days) | 
| Ventilator-Free Days | Number of days without mechanical ventilation | ICU stay (an average of 21 days) | 
| Hospital-free days | Number of days outside hospital | Within the first 28 days | 
| Glasgow Outcome Scale Extended (GOSE) |  | Day 28 | 
| Hospitalisation status |  | Day 28 | 
| Cost of the strategy |  | Day 8 and Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute traumatic coagulopathy, Hemostasis, Severe hemorrhage