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

Phase 3

Completed

• Conditions: Shock, Hemorrhagic
• Interventions: Drug: Pro-Thrombin Concentrate Complex; Drug: NaCl 0.9%

• Registration Number: NCT03218722
• Lead Sponsor: University Hospital, Grenoble

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-07-12
• Study First Submitted QC: 2017-07-12
• Study First Posted: 2017-07-14
• Study Start: 2017-12-29
• Primary Completion: 2021-08-31
• Study Completion: 2022-06-15
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-07
• Last Update Posted: 2022-11-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 350

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...)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PCC treatment	Pro-Thrombin Concentrate Complex	Conventional strategy for ATC management in addition to of intravenous Pro-Thrombin Concentrate Complex (25IU/kg factor IX)
Placebo treatment	NaCl 0.9%	Conventional strategy for ATC management without PCC (NaCl 0.9%)

Primary Outcome Measures

Name	Time	Method
Labile blood products transfused in the first 24 hours	24 hours following hospital admission	This outcome is measured in number of bags administered

Secondary Outcome Measures

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

Trial Locations

Locations (12)

Lille University Hospital; 🇫🇷 Lille, France

Nantes University Hospital; 🇫🇷 Nantes, France

AP-HM - Marseille Nord; 🇫🇷 Marseille, France

AP-HP Beaujon; 🇫🇷 Clichy, France

HCL - Hôpital Edouard Herriot; 🇫🇷 Lyon, France

AP-HP Pitié Salpetrière; 🇫🇷 Paris, France

Grenoble University Hospital; 🇫🇷 Grenoble, France

AP-HP Kremlin Bicêtre; 🇫🇷 Le Kremlin-Bicêtre, France

Montpellier University Hospital; 🇫🇷 Montpellier, France

Strasbourg University Hospital; 🇫🇷 Strasbourg, France

Annecy University Hospital; 🇫🇷 Annecy, France

HCL - Lyon Sud; 🇫🇷 Pierre-Bénite, France