Shock, HemorrhagicPhase 3PROCOAGNCT03218722
Early Administration of Prothrombin Concentrate Complex in Patients With Acute Hemorrhage Following Severe Trauma
A Phase 3 study testing Pro-Thrombin Concentrate Complex and NaCl 0.9% in people with Shock, Hemorrhagic, run by University Hospital, Grenoble at 12 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Shock, Hemorrhagic
- What is being tested?
- Pro-Thrombin Concentrate Complex and NaCl 0.9%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 350 participants
- Where
- 12 sitesFrance
- Study dates
- 29 Dec 2017to 15 Jun 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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®
Show all 10Show fewer
- 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...)
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
France12 sites
Annecy University Hospital
Annecy, 74370
AP-HP Beaujon
Clichy, 92110
Grenoble University Hospital
Grenoble
AP-HP Kremlin Bicêtre
Le Kremlin-Bicêtre, 94275
Lille University Hospital
Lille, 59035
HCL - Hôpital Edouard Herriot
Lyon, 69003
AP-HM - Marseille Nord
Marseille, 13915
Montpellier University Hospital
Montpellier, 34090
Nantes University Hospital
Nantes, 44 093
AP-HP Pitié Salpetrière
Paris, 75651
HCL - Lyon Sud
Pierre-Bénite, 69495
Strasbourg University Hospital
Strasbourg, 67000
About this study
Official title: 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.
Read more
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
- Being tested
- Pro-Thrombin Concentrate Complex, NaCl 0.9%
- Keywords
- Acute traumatic coagulopathy, Hemostasis, Severe hemorrhage
- Medical subject headings
- Shock, Hemorrhagic, Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pro-Thrombin Concentrate ComplexDrug
Also called KANOKAD
Patient at risk of massive hemorrhage will be managed with standard care with 1ml/kg PCC.
NaCl 0.9%Drug
Patient at risk of massive hemorrhage will be managed with standard care with 1ml/kg Saline solution.
| Study group | Role | What they receive |
|---|---|---|
| PCC treatment | Experimental | Conventional strategy for ATC management in addition to of intravenous Pro-Thrombin Concentrate Complex (25IU/kg factor IX) Receives: Drug: Pro-Thrombin Concentrate Complex |
| Placebo treatment | Placebo comparator | Conventional strategy for ATC management without PCC (NaCl 0.9%) Receives: Drug: NaCl 0.9% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Labile blood products transfused in the first 24 hours
This outcome is measured in number of bags administered
Measured: 24 hours following hospital admission
Secondary outcomes (13)
RBC (Red Blood Cells) transfused in the first 24 hours
This outcome is measured in number of bags administered
Measured: 24 hours following hospital admission
FFP transfused in the first 24 hours
This outcome is measured in number of bags administered
Measured: 24 hours following hospital admission
Platelets transfused in the first 24 hours
This outcome is measured in number of bags administered
Measured: 24 hours following hospital admission
Time to achieve Prothrombin ratio < 1.5
Measured: 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
Measured: Within the first 24 hours following admission
Thrombo-embolic events
Measured: ICU stay (an average of 28 days)
Mortality
Measured: 24 hours and Day 28
ICU-free days
Number of in-hospital days outside Intensive Care Unit (ICU)
Measured: Hospital stay (an average of 28 days)
Ventilator-Free Days
Number of days without mechanical ventilation
Measured: ICU stay (an average of 21 days)
Hospital-free days
Number of days outside hospital
Measured: Within the first 28 days
Glasgow Outcome Scale Extended (GOSE)
Measured: Day 28
Hospitalisation status
Measured: Day 28
Cost of the strategy
Measured: Day 8 and Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2017
- Study start29 Dec 2017
- Primary completion31 Aug 2021
- Study completion15 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Shock, HemorrhagicStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 350 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pierre BOUZAT, Principal investigator, CHU Grenoble Alpes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03218722
- Sponsor's protocol ID
- 38RC16.046
- Acronym
- PROCOAG
- Status last verified
- Nov 2022
- First submitted
- 12 Jul 2017
- Last updated
- 8 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36942533Bouzat 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.
PubMed 34530886
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Early Administration of Prothrombin Concentrate Complex in Patients With Acute Hemorrhage Following Severe Trauma
- ClinicalTrials.gov ID
- NCT03218722
- Acronym / sponsor ID
- PROCOAG / 38RC16.046
- Conditions
- Shock, Hemorrhagic
- Keywords
- Acute traumatic coagulopathy, Hemostasis, Severe hemorrhage
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 350 participants (actual)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Study start
- 29 Dec 2017 (actual)
- Primary completion
- 31 Aug 2021 (actual)
- Study completion
- 15 Jun 2022 (actual)
- First posted
- 14 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PCC treatment | Experimental | Drug: Pro-Thrombin Concentrate ComplexConventional strategy for ATC management in addition to of intravenous Pro-Thrombin Concentrate Complex (25IU/kg factor IX) |
| Placebo treatment | Placebo comparator | Drug: NaCl 0.9%Conventional strategy for ATC management without PCC (NaCl 0.9%) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pro-Thrombin Concentrate ComplexAlso: KANOKADPatient at risk of massive hemorrhage will be managed with standard care with 1ml/kg PCC. | Drug | PCC treatment |
| NaCl 0.9%Patient at risk of massive hemorrhage will be managed with standard care with 1ml/kg Saline solution. | Drug | Placebo treatment |
Primary outcome
Labile blood products transfused in the first 24 hours
Time frame: 24 hours following hospital admission
This outcome is measured in number of bags administered
13 secondary outcomes
RBC (Red Blood Cells) transfused in the first 24 hours
Time frame: 24 hours following hospital admission
FFP transfused in the first 24 hours
Time frame: 24 hours following hospital admission
Platelets transfused in the first 24 hours
Time frame: 24 hours following hospital admission
Time to achieve Prothrombin ratio < 1.5
Time frame: Within the first 24 hours
Time to hemostasis
Time frame: Within the first 24 hours following admission
Thrombo-embolic events
Time frame: ICU stay (an average of 28 days)
Mortality
Time frame: 24 hours and Day 28
ICU-free days
Time frame: Hospital stay (an average of 28 days)
Ventilator-Free Days
Time frame: ICU stay (an average of 21 days)
Hospital-free days
Time frame: Within the first 28 days
Glasgow Outcome Scale Extended (GOSE)
Time frame: Day 28
Hospitalisation status
Time frame: Day 28
Cost of the strategy
Time frame: Day 8 and Day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2022.
- Derived from this study: PubMed 36942533Bouzat 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.
- Derived from this study: PubMed 34530886Bouzat 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pierre BOUZAT principal investigator
CHU Grenoble Alpes
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pro-Thrombin Concentrate Complex and NaCl 0.9% in people with Shock, Hemorrhagic, run by University Hospital, Grenoble at 12 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Labile blood products transfused in the first 24 hours (time frame: 24 hours following hospital admission). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03218722, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2022.