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

NCT03218722 | Completed Phase 3 DMC

• 1 other identifier: 38RC16.046
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 12

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

Keywords

Acute traumatic coagulopathy; Hemostasis; Severe hemorrhage

Outcome Measures

Primary Outcomes (1)

• Labile blood products transfused in the first 24 hours

  This outcome is measured in number of bags administered

  24 hours following hospital admission

Secondary Outcomes (13)

• RBC (Red Blood Cells) transfused in the first 24 hours

  24 hours following hospital admission

• FFP transfused in the first 24 hours

  24 hours following hospital admission

• Platelets transfused in the first 24 hours

  24 hours following hospital admission

• Time to achieve Prothrombin ratio < 1.5

  Within the first 24 hours

• Time to hemostasis

  Within the first 24 hours following admission

Study Arms (2)

PCC treatment

EXPERIMENTAL

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

Drug: Pro-Thrombin Concentrate Complex

Placebo treatment

PLACEBO COMPARATOR

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

Drug: NaCl 0.9%

Interventions

Pro-Thrombin Concentrate Complex DRUG

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

Also known as: KANOKAD

PCC treatment

NaCl 0.9% DRUG

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

Placebo treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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...)

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Study Sites (12)

Annecy University Hospital

Annecy, 74370, France

Location

AP-HP Beaujon

Clichy, 92110, France

Location

Grenoble University Hospital

Grenoble, France

Location

AP-HP Kremlin Bicêtre

Le Kremlin-Bicêtre, 94275, France

Location

Lille University Hospital

Lille, 59035, France

Location

HCL - Hôpital Edouard Herriot

Lyon, 69003, France

Location

AP-HM - Marseille Nord

Marseille, 13915, France

Location

Montpellier University Hospital

Montpellier, 34090, France

Location

Nantes University Hospital

Nantes, 44 093, France

Location

AP-HP Pitié Salpetrière

Paris, 75651, France

Location

HCL - Lyon Sud

Pierre-Bénite, 69495, France

Location

Strasbourg University Hospital

Strasbourg, 67000, France

Location

Related Publications (2)

• 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.

  PMID: 36942533 DERIVED

• 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.

  PMID: 34530886 DERIVED

MeSH Terms

Conditions

Shock, Hemorrhagic; Hemorrhage

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Pierre BOUZAT

  CHU Grenoble Alpes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2017
• First Posted: July 14, 2017
• Study Start: December 29, 2017
• Primary Completion: August 31, 2021
• Study Completion: June 15, 2022
• Last Updated: November 8, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (12)