Early Administration of Prothrombin Concentrate Complex in Patients With Acute Hemorrhage Following Severe Trauma (PROCOAG)
Primary Purpose
Shock, Hemorrhagic
Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Pro-Thrombin Concentrate Complex
NaCl 0.9%
Sponsored by
About this trial
This is an interventional treatment trial for Shock, Hemorrhagic focused on measuring Acute traumatic coagulopathy, Hemostasis, Severe hemorrhage
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...)
Sites / Locations
- Annecy University Hospital
- AP-HP Beaujon
- Grenoble University Hospital
- AP-HP Kremlin Bicêtre
- Lille University Hospital
- HCL - Hôpital Edouard Herriot
- AP-HM - Marseille Nord
- Montpellier University Hospital
- Nantes University Hospital
- AP-HP Pitié Salpetrière
- HCL - Lyon Sud
- Strasbourg University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
PCC treatment
Placebo treatment
Arm Description
Conventional strategy for ATC management in addition to of intravenous Pro-Thrombin Concentrate Complex (25IU/kg factor IX)
Conventional strategy for ATC management without PCC (NaCl 0.9%)
Outcomes
Primary Outcome Measures
Labile blood products transfused in the first 24 hours
This outcome is measured in number of bags administered
Secondary Outcome Measures
RBC (Red Blood Cells) transfused in the first 24 hours
This outcome is measured in number of bags administered
FFP transfused in the first 24 hours
This outcome is measured in number of bags administered
Platelets transfused in the first 24 hours
This outcome is measured in number of bags administered
Time to achieve Prothrombin ratio < 1.5
Time to hemostasis
Hemostasis is defined as bleeding control in the surgical field or resolution of contrast blush after embolization during interventional radiology
Thrombo-embolic events
Mortality
ICU-free days
Number of in-hospital days outside Intensive Care Unit (ICU)
Ventilator-Free Days
Number of days without mechanical ventilation
Hospital-free days
Number of days outside hospital
Glasgow Outcome Scale Extended (GOSE)
Hospitalisation status
Cost of the strategy
Full Information
NCT ID
NCT03218722
First Posted
July 12, 2017
Last Updated
November 7, 2022
Sponsor
University Hospital, Grenoble
1. Study Identification
Unique Protocol Identification Number
NCT03218722
Brief Title
Early Administration of Prothrombin Concentrate Complex in Patients With Acute Hemorrhage Following Severe Trauma
Acronym
PROCOAG
Official Title
Impact of Early Administration of Prothrombin Concentrate Complex in Patients With Acute Hemorrhage Following Severe Trauma
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
December 29, 2017 (Actual)
Primary Completion Date
August 31, 2021 (Actual)
Study Completion Date
June 15, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Grenoble
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Shock, Hemorrhagic
Keywords
Acute traumatic coagulopathy, Hemostasis, Severe hemorrhage
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
350 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PCC treatment
Arm Type
Experimental
Arm Description
Conventional strategy for ATC management in addition to of intravenous Pro-Thrombin Concentrate Complex (25IU/kg factor IX)
Arm Title
Placebo treatment
Arm Type
Placebo Comparator
Arm Description
Conventional strategy for ATC management without PCC (NaCl 0.9%)
Intervention Type
Drug
Intervention Name(s)
Pro-Thrombin Concentrate Complex
Other Intervention Name(s)
KANOKAD
Intervention Description
Patient at risk of massive hemorrhage will be managed with standard care with 1ml/kg PCC.
Intervention Type
Drug
Intervention Name(s)
NaCl 0.9%
Intervention Description
Patient at risk of massive hemorrhage will be managed with standard care with 1ml/kg Saline solution.
Primary Outcome Measure Information:
Title
Labile blood products transfused in the first 24 hours
Description
This outcome is measured in number of bags administered
Time Frame
24 hours following hospital admission
Secondary Outcome Measure Information:
Title
RBC (Red Blood Cells) transfused in the first 24 hours
Description
This outcome is measured in number of bags administered
Time Frame
24 hours following hospital admission
Title
FFP transfused in the first 24 hours
Description
This outcome is measured in number of bags administered
Time Frame
24 hours following hospital admission
Title
Platelets transfused in the first 24 hours
Description
This outcome is measured in number of bags administered
Time Frame
24 hours following hospital admission
Title
Time to achieve Prothrombin ratio < 1.5
Time Frame
Within the first 24 hours
Title
Time to hemostasis
Description
Hemostasis is defined as bleeding control in the surgical field or resolution of contrast blush after embolization during interventional radiology
Time Frame
Within the first 24 hours following admission
Title
Thrombo-embolic events
Time Frame
ICU stay (an average of 28 days)
Title
Mortality
Time Frame
24 hours and Day 28
Title
ICU-free days
Description
Number of in-hospital days outside Intensive Care Unit (ICU)
Time Frame
Hospital stay (an average of 28 days)
Title
Ventilator-Free Days
Description
Number of days without mechanical ventilation
Time Frame
ICU stay (an average of 21 days)
Title
Hospital-free days
Description
Number of days outside hospital
Time Frame
Within the first 28 days
Title
Glasgow Outcome Scale Extended (GOSE)
Time Frame
Day 28
Title
Hospitalisation status
Time Frame
Day 28
Title
Cost of the strategy
Time Frame
Day 8 and Day 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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...)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pierre BOUZAT
Organizational Affiliation
CHU Grenoble Alpes
Official's Role
Principal Investigator
Facility Information:
Facility Name
Annecy University Hospital
City
Annecy
ZIP/Postal Code
74370
Country
France
Facility Name
AP-HP Beaujon
City
Clichy
ZIP/Postal Code
92110
Country
France
Facility Name
Grenoble University Hospital
City
Grenoble
Country
France
Facility Name
AP-HP Kremlin Bicêtre
City
Le Kremlin-Bicêtre
ZIP/Postal Code
94275
Country
France
Facility Name
Lille University Hospital
City
Lille
ZIP/Postal Code
59035
Country
France
Facility Name
HCL - Hôpital Edouard Herriot
City
Lyon
ZIP/Postal Code
69003
Country
France
Facility Name
AP-HM - Marseille Nord
City
Marseille
ZIP/Postal Code
13915
Country
France
Facility Name
Montpellier University Hospital
City
Montpellier
ZIP/Postal Code
34090
Country
France
Facility Name
Nantes University Hospital
City
Nantes
ZIP/Postal Code
44 093
Country
France
Facility Name
AP-HP Pitié Salpetrière
City
Paris
ZIP/Postal Code
75651
Country
France
Facility Name
HCL - Lyon Sud
City
Pierre-Bénite
ZIP/Postal Code
69495
Country
France
Facility Name
Strasbourg University Hospital
City
Strasbourg
ZIP/Postal Code
67000
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34530886
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.
Results Reference
derived
Learn more about this trial
Early Administration of Prothrombin Concentrate Complex in Patients With Acute Hemorrhage Following Severe Trauma
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