Clinical trial NCT03218722: Early Administration of Prothrombin Concentrate Complex in Patients With Acute Hemorrhage Following Severe Trauma
Official title: Impact of Early Administration of Prothrombin Concentrate Complex in Patients With Acute Hemorrhage Following Severe Trauma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Shock, Hemorrhagic
Keywords: Acute traumatic coagulopathy
Hemostasis
Severe hemorrhage
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
First posted: 2017-07-14
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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...)

Primary outcomes:
measure: Labile blood products transfused in the first 24 hours
timeFrame: 24 hours following hospital admission
Secondary outcomes:
measure: RBC (Red Blood Cells) transfused in the first 24 hours
timeFrame: 24 hours following hospital admission
measure: FFP transfused in the first 24 hours
timeFrame: 24 hours following hospital admission
measure: Platelets transfused in the first 24 hours
timeFrame: 24 hours following hospital admission
measure: Time to achieve Prothrombin ratio < 1.5
timeFrame: Within the first 24 hours
measure: Time to hemostasis
timeFrame: Within the first 24 hours following admission
measure: Thrombo-embolic events
timeFrame: ICU stay (an average of 28 days)
measure: Mortality
timeFrame: 24 hours and Day 28
measure: ICU-free days
timeFrame: Hospital stay (an average of 28 days)
measure: Ventilator-Free Days
timeFrame: ICU stay (an average of 21 days)
measure: Hospital-free days
timeFrame: Within the first 28 days
measure: Glasgow Outcome Scale Extended (GOSE)
timeFrame: Day 28
measure: Hospitalisation status
timeFrame: Day 28
measure: Cost of the strategy
timeFrame: Day 8 and Day 28
Other outcomes:
Locations:
city: Annecy
country: France
facility: Annecy University Hospital
city: Clichy
country: France
facility: AP-HP Beaujon
city: Grenoble
country: France
facility: Grenoble University Hospital
city: Le Kremlin-Bicêtre
country: France
facility: AP-HP Kremlin Bicêtre
city: Lille
country: France
facility: Lille University Hospital
city: Lyon
country: France
facility: HCL - Hôpital Edouard Herriot
city: Marseille
country: France
facility: AP-HM - Marseille Nord
city: Montpellier
country: France
facility: Montpellier University Hospital
city: Nantes
country: France
facility: Nantes University Hospital
city: Paris
country: France
facility: AP-HP Pitié Salpetrière
city: Pierre-Bénite
country: France
facility: HCL - Lyon Sud
city: Strasbourg
country: France
facility: Strasbourg University Hospital
Study officials:
affiliation: CHU Grenoble Alpes
name: Pierre BOUZAT
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.