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

NCT ID: NCT03218722

Last Updated: 2022-11-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-29
• Study Completion Date: 2022-06-15

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.

Conditions

Shock, Hemorrhagic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

PCC treatment

Conventional strategy for ATC management in addition to of intravenous Pro-Thrombin Concentrate Complex (25IU/kg factor IX)

Group Type: EXPERIMENTAL

Pro-Thrombin Concentrate Complex

Intervention Type: DRUG

Patient at risk of massive hemorrhage will be managed with standard care with 1ml/kg PCC.

Placebo treatment

Conventional strategy for ATC management without PCC (NaCl 0.9%)

Group Type: PLACEBO_COMPARATOR

NaCl 0.9%

Intervention Type: DRUG

Patient at risk of massive hemorrhage will be managed with standard care with 1ml/kg Saline solution.

Interventions

Pro-Thrombin Concentrate Complex

Patient at risk of massive hemorrhage will be managed with standard care with 1ml/kg PCC.

Intervention Type: DRUG

NaCl 0.9%

Patient at risk of massive hemorrhage will be managed with standard care with 1ml/kg Saline solution.

Intervention Type: DRUG

Other Intervention Names

KANOKAD

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...)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Grenoble

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pierre BOUZAT

Role: PRINCIPAL_INVESTIGATOR

CHU Grenoble Alpes

Locations

Annecy University Hospital

Annecy, , France

AP-HP Beaujon

Clichy, , France

Grenoble University Hospital

Grenoble, , France

AP-HP Kremlin Bicêtre

Le Kremlin-Bicêtre, , France

Lille University Hospital

Lille, , France

HCL - Hôpital Edouard Herriot

Lyon, , France

AP-HM - Marseille Nord

Marseille, , France

Montpellier University Hospital

Montpellier, , France

Nantes University Hospital

Nantes, , France

AP-HP Pitié Salpetrière

Paris, , France

HCL - Lyon Sud

Pierre-Bénite, , France

Strasbourg University Hospital

Strasbourg, , France

Countries

France

References

Bouzat P, Charbit J, Abback PS, Huet-Garrigue D, Delhaye N, Leone M, Marcotte G, David JS, Levrat A, Asehnoune K, Pottecher J, Duranteau J, Courvalin E, Adolle A, Sourd D, Bosson JL, Riou B, Gauss T, Payen JF; PROCOAG Study Group. Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion: The PROCOAG Randomized Clinical Trial. JAMA. 2023 Apr 25;329(16):1367-1375. doi: 10.1001/jama.2023.4080.

Reference Type: DERIVED

PMID: 36942533 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34530886 (View on PubMed)

Other Identifiers

38RC16.046

Identifier Type: -

Identifier Source: org_study_id