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

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

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.

Study Overview

• Status: Completed
• Conditions: Shock, Hemorrhagic
• Intervention / Treatment: Drug: Pro-Thrombin Concentrate Complex; Drug: NaCl 0.9%

• Study Type: Interventional
• Enrollment (Actual): 350
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Annecy, France, 74370
    • Annecy University Hospital
  • Clichy, France, 92110
    • AP-HP Beaujon
  • Grenoble, France
    • Grenoble University Hospital
  • Le Kremlin-Bicêtre, France, 94275
    • AP-HP Kremlin Bicêtre
  • Lille, France, 59035
    • Lille University Hospital
  • Lyon, France, 69003
    • HCL - Hôpital Edouard Herriot
  • Marseille, France, 13915
    • AP-HM - Marseille Nord
  • Montpellier, France, 34090
    • Montpellier University Hospital
  • Nantes, France, 44 093
    • Nantes university hospital
  • Paris, France, 75651
    • AP-HP Pitié Salpetrière
  • Pierre-Bénite, France, 69495
    • HCL - Lyon Sud
  • Strasbourg, France, 67000
    • Strasbourg university hospital

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Investigators: Principal Investigator: Pierre BOUZAT, Chu Grenoble Alpes

Publications and helpful links

General Publications

• Bouzat P, Bosson JL, David JS, Riou B, Duranteau J, Payen JF; PROCOAG study group. Four-factor prothrombin complex concentrate to reduce allogenic blood product transfusion in patients with major trauma, the PROCOAG trial: study protocol for a randomized multicenter double-blind superiority study. Trials. 2021 Sep 16;22(1):634. doi: 10.1186/s13063-021-05524-x.

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2017
• Primary Completion (Actual): August 31, 2021
• Study Completion (Actual): June 15, 2022

Study Registration Dates

• First Submitted: July 12, 2017
• First Submitted That Met QC Criteria: July 12, 2017
• First Posted (Actual): July 14, 2017

Study Record Updates

• Last Update Posted (Actual): November 8, 2022
• Last Update Submitted That Met QC Criteria: November 7, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Hemostasis; Acute traumatic coagulopathy; Severe hemorrhage
• Additional Relevant MeSH Terms: Pathologic Processes; Shock; Hemorrhage; Shock, Hemorrhagic; Hemostatics; Coagulants; Thrombin
• Other Study ID Numbers: 38RC16.046

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