Intracranial Hemorrhage, TraumaticNCT02429453
FFP Versus PCC in Intracranial Hemorrhage
A study testing Four Factor Prothrombin Complex Concentrate and Fresh Frozen Plasma in people with Intracranial Hemorrhage, Traumatic and Intracranial Hemorrhage, Spontaneous, run by University of Utah at 1 site in United States.
Trial summary
The goal of this study will be to determine whether PCC confers any benefits over FFP in traumatic and spontaneous intracranial hemorrhage with respect to multiple factors including time to correction, absolute international normalized ratio correction amount, cost, need for surgical intervention, and radiographic… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intracranial Hemorrhage, Traumatic, Intracranial Hemorrhage, Spontaneous
- What is being tested?
- Four Factor Prothrombin Complex Concentrate and Fresh Frozen Plasma
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2015to Mar 2016
- Phase
- Interventional
- 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
- Coumadin use
- INR of 2.0 or higher on arrival at the study center
- Evidence on cranial imaging of spontaneous intracranial hemorrhage, subdural hematoma, epidural hematoma, cerebral contusion, traumatic subarachnoid hemorrhage, or traumatic intraparenchymal hemorrhage
Who cannot join
- Unable to obtain consent
- Estimated survival <24 hours
- Hypersensitivity to 4 factor prothrombin complex concentrate
- Concomitant use of novel vitamin K antagonists
- Religious/social prohibition to receiving blood products
- Need for emergent, non-neurosurgical operative intervention
- Mechanical heart valves
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Utah Medical Center
Salt Lake City, Utah, 84132
About this study
Official title: Fresh Frozen Plasma Versus Four Factor Prothrombin Complex Concentrate for Reversal of Vitamin K Antagonists in Intracranial Hemorrhage
The goal of this study will be to determine whether PCC confers any benefits over FFP in traumatic and spontaneous intracranial hemorrhage with respect to multiple factors including time to correction, absolute international normalized ratio correction amount, cost, need for surgical intervention, and radiographic bleed expansion through a prospective, randomized control trial.
Read the detailed description
Vitamin K antagonists in general and Coumadin in particular remains the most common form of outpatient anticoagulation in patients today. Despite the therapeutic benefits of these agents, bleeding in general and intracranial bleeding in particular are significant risks associated with these medications. Intracranial bleeding on oral anticoagulation agents are associated with a 20% increase in 30 day mortality versus non-anticoagulated controls, and rapid reversal of vitamin K antagonists in this population has been shown to have survival benefits.
Historically, vitamin K antagonists have been reversed using fresh frozen plasma (FFP) transfusions which, though effective, often incur delays due to the time required to obtain a type \& screen, thaw the product, and administer the product to the patient. In 2013, the FDA approved 4-factor prothrombin complex (PCC), a concentrate of factors II, VII, IX, X, protein C and protein S for use as a method for correcting vitamin K antagonist related coagulopathy. Though large, prospective randomized control trials have demonstrated efficacy and safety in a general population of all-comers bleeding, there is very little literature regarding the benefits of PCC versus FFP in the traumatic and spontaneous intracranial hemorrhage population.
Current standard of care in patients with traumatic and spontaneous intracranial hemorrhage who are on vitamin K antagonists is to reverse the effect of these agents with FFP or PCC. The choice of which agent to use is currently determined by both availability of each agent and surgeon preference. For this study, there will be an equal likelihood of either treatment being given.
The goal of this study will be to determine whether PCC confers any benefits over FFP in traumatic and spontaneous intracranial hemorrhage with respect to multiple factors including time to correction, absolute international normalized ratio correction amount, cost, need for surgical intervention, and radiographic bleed expansion through a prospective, randomized control trial.
- Being tested
- Four Factor Prothrombin Complex Concentrate, Fresh Frozen Plasma
- Keywords
- Warfarin, Traumatic intracranial hemorrhage, prothrombin complex concentrate, fresh frozen plasma, Spontaneous intracranial hemorrhage
- Medical subject headings
- Intracranial Hemorrhage, Traumatic, Intracranial Hemorrhages, Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Four Factor Prothrombin Complex ConcentrateDrug
Also called Kcentra
A purified, non-activated prothrombin complex concentrate containing factors II, VII, IX and X and proteins C \& S
Fresh Frozen PlasmaBiological
A pooled collection of plasma from donors
| Study group | Role | What they receive |
|---|---|---|
| Fresh Frozen Plasma | Active comparator | Administration of a single dose of fresh frozen plasma based on INR per the following regimen: 2U for INR of 2-2.5; 3U for INR of 2.5-3; 4U for INR of 3-3.5; 5U for INR of 3.5-4; 6U for INR of 4+ Receives: Biological: Fresh Frozen Plasma |
| Four Factor Prothrombin Complex Concentrate | Experimental | Administration of a single dose of four factor prothrombin complex concentrate per the following dosing regimen: 25 U/kg for INR of 2-4; 35 U/kg for INR of 4-6; 50 U/kg for INR of 6+; maximum dosing weight of 100kg, patients may be dispensed +/- 10% of ordered dose Receives: Drug: Four Factor Prothrombin Complex Concentrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rapid reversal of warfarin as measured by international normalized ratio (INR) drawn at 30 minutes after transfusion
INR level 30 minutes after transfusion completion of FFP or 4 factor prothrombin complex concentrate
Measured: 30 minutes after transfusion completion
Secondary outcomes (11)
Radiographic expansion of traumatic intracerebral hemorrhage as measured by CT scan within 24 hours of presentation
Expansion of blood on repeat CT scan of >10%
Measured: 24 hours after presentation
Timing of reversal of warfarin as measured by INR drawn at 3 hours, 8 hours and 24 hours after transfusion
INR level at 3 hours, 8 hours and 24 hours after transfusion completion of FFP or prothrombin complex concentrate
Measured: 3-24 hours after completion of FFP or 4 factor prothrombin complex concentrate transfusion
Thromboelastography response as measured by results of ROTEM analysis at 30 minutes and 24 hours after transfusion
Results of ROTEM analysis at 30 minutes and 24 hours after transfusion
Measured: 30 minutes and 24 hours after completion of FFP or 4 factor prothrombin complex concentrate transfusion
Absolute INR reversal as measured by INR drawn 24 hours after transfusion
Difference between initial INR and INR 24 hours after completion of transfusion
Measured: 24 hours after completion of FFP or 4 factor prothrombin complex concentrate transfusion
Need for operative intervention as measured by need for neurosurgical procedure during the hospitalization
Need for operative intervention during hospitalization related to initial trauma
Measured: During duration of hospital stay, an expected average of 1 week
Estimated blood loss during any neurosurgical procedure
Estimated blood loss during any neurosurgical interventions during the hospitalization
Measured: During duration of hospital stay, an expected average of 1 week
Further transfusion needs as measured by number of units of blood/platelet/plasma products transfused during the hospitalization
Need for blood product transfusions during hospitalization
Measured: During duration of hospital stay, an expected average of 1 week
In hospital mortality
Mortality during hospital stay
Measured: During duration of hospital stay, an expected average of 1 week
Total hospital cost
Total cost of hospital stay based on hospital charges
Measured: During duration of hospital stay, an expected average of 1 week
30 day outcome as measured by the Glasgow outcome score
Glasgow outcome score 30 days after discharge
Measured: 30 days after discharge
Complications as measured by development of deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, unanticipated intubation, heart failure, or need for aggressive diuresis during the hospitalization
Development of deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, unanticipated intubation, heart failure, or need for aggressive diuresis
Measured: During duration of hospital stay, an expected average of 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2015 (estimated)
- Study startApr 2015
- Primary completionMar 2016
- Study completionMar 2016
Why it stopped: Lack of enrolment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Intracranial Hemorrhage, TraumaticStudies of the same condition, open and under way.
- More trials run by University of UtahThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jian Guan, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02429453
- Sponsor's protocol ID
- IRB_00078143
- Status last verified
- Nov 2016
- First submitted
- 21 Apr 2015
- Last updated
- 16 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Eilertsen H, Menon CS, Law ZK, Chen C, Bath PM, Steiner T, Desborough MJ, Sandset EC, Sprigg N, Al-Shahi Salman R. Haemostatic therapies for stroke due to acute, spontaneous intracerebral haemorrhage. Cochrane Database Syst Rev. 2023 Oct 23;10(10):CD005951. doi: 10.1002/14651858.CD005951.pub5.
PubMed 37870112
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fresh Frozen Plasma Versus Four Factor Prothrombin Complex Concentrate for Reversal of Vitamin K Antagonists in Intracranial Hemorrhage
- ClinicalTrials.gov ID
- NCT02429453
- Acronym / sponsor ID
- IRB_00078143
- Keywords
- Warfarin, Traumatic intracranial hemorrhage, prothrombin complex concentrate, fresh frozen plasma, Spontaneous intracranial hemorrhage
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of enrolment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- Apr 2015
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 29 Apr 2015 (estimated)
- 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.
The goal of this study will be to determine whether PCC confers any benefits over FFP in traumatic and spontaneous intracranial hemorrhage with respect to multiple factors including time to correction, absolute international normalized ratio correction amount, cost, need for surgical intervention, and radiographic bleed expansion through a prospective, randomized control trial.
Detailed description
Vitamin K antagonists in general and Coumadin in particular remains the most common form of outpatient anticoagulation in patients today. Despite the therapeutic benefits of these agents, bleeding in general and intracranial bleeding in particular are significant risks associated with these medications. Intracranial bleeding on oral anticoagulation agents are associated with a 20% increase in 30 day mortality versus non-anticoagulated controls, and rapid reversal of vitamin K antagonists in this population has been shown to have survival benefits.
Historically, vitamin K antagonists have been reversed using fresh frozen plasma (FFP) transfusions which, though effective, often incur delays due to the time required to obtain a type \& screen, thaw the product, and administer the product to the patient. In 2013, the FDA approved 4-factor prothrombin complex (PCC), a concentrate of factors II, VII, IX, X, protein C and protein S for use as a method for correcting vitamin K antagonist related coagulopathy. Though large, prospective randomized control trials have demonstrated efficacy and safety in a general population of all-comers bleeding, there is very little literature regarding the benefits of PCC versus FFP in the traumatic and spontaneous intracranial hemorrhage population.
Current standard of care in patients with traumatic and spontaneous intracranial hemorrhage who are on vitamin K antagonists is to reverse the effect of these agents with FFP or PCC. The choice of which agent to use is currently determined by both availability of each agent and surgeon preference. For this study, there will be an equal likelihood of either treatment being given.
The goal of this study will be to determine whether PCC confers any benefits over FFP in traumatic and spontaneous intracranial hemorrhage with respect to multiple factors including time to correction, absolute international normalized ratio correction amount, cost, need for surgical intervention, and radiographic bleed expansion through a prospective, randomized control trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fresh Frozen Plasma | Active comparator | Biological: Fresh Frozen PlasmaAdministration of a single dose of fresh frozen plasma based on INR per the following regimen: 2U for INR of 2-2.5; 3U for INR of 2.5-3; 4U for INR of 3-3.5; 5U for INR of 3.5-4; 6U for INR of 4+ |
| Four Factor Prothrombin Complex Concentrate | Experimental | Drug: Four Factor Prothrombin Complex ConcentrateAdministration of a single dose of four factor prothrombin complex concentrate per the following dosing regimen: 25 U/kg for INR of 2-4; 35 U/kg for INR of 4-6; 50 U/kg for INR of 6+; maximum dosing weight of 100kg, patients may be dispensed +/- 10% of ordered dose |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Coumadin use
- INR of 2.0 or higher on arrival at the study center
- Evidence on cranial imaging of spontaneous intracranial hemorrhage, subdural hematoma, epidural hematoma, cerebral contusion, traumatic subarachnoid hemorrhage, or traumatic intraparenchymal hemorrhage
Key exclusion criteria (7 listed)
- Unable to obtain consent
- Estimated survival <24 hours
- Hypersensitivity to 4 factor prothrombin complex concentrate
- Concomitant use of novel vitamin K antagonists
- Religious/social prohibition to receiving blood products
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 |
|---|---|---|
| Four Factor Prothrombin Complex ConcentrateAlso: KcentraA purified, non-activated prothrombin complex concentrate containing factors II, VII, IX and X and proteins C \& S | Drug | Four Factor Prothrombin Complex Concentrate |
| Fresh Frozen PlasmaA pooled collection of plasma from donors | Biological | Fresh Frozen Plasma |
Primary outcome
Rapid reversal of warfarin as measured by international normalized ratio (INR) drawn at 30 minutes after transfusion
Time frame: 30 minutes after transfusion completion
INR level 30 minutes after transfusion completion of FFP or 4 factor prothrombin complex concentrate
11 secondary outcomes
Radiographic expansion of traumatic intracerebral hemorrhage as measured by CT scan within 24 hours of presentation
Time frame: 24 hours after presentation
Timing of reversal of warfarin as measured by INR drawn at 3 hours, 8 hours and 24 hours after transfusion
Time frame: 3-24 hours after completion of FFP or 4 factor prothrombin complex concentrate transfusion
Thromboelastography response as measured by results of ROTEM analysis at 30 minutes and 24 hours after transfusion
Time frame: 30 minutes and 24 hours after completion of FFP or 4 factor prothrombin complex concentrate transfusion
Absolute INR reversal as measured by INR drawn 24 hours after transfusion
Time frame: 24 hours after completion of FFP or 4 factor prothrombin complex concentrate transfusion
Need for operative intervention as measured by need for neurosurgical procedure during the hospitalization
Time frame: During duration of hospital stay, an expected average of 1 week
Estimated blood loss during any neurosurgical procedure
Time frame: During duration of hospital stay, an expected average of 1 week
Further transfusion needs as measured by number of units of blood/platelet/plasma products transfused during the hospitalization
Time frame: During duration of hospital stay, an expected average of 1 week
In hospital mortality
Time frame: During duration of hospital stay, an expected average of 1 week
Total hospital cost
Time frame: During duration of hospital stay, an expected average of 1 week
30 day outcome as measured by the Glasgow outcome score
Time frame: 30 days after discharge
Complications as measured by development of deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, unanticipated intubation, heart failure, or need for aggressive diuresis during the hospitalization
Time frame: During duration of hospital stay, an expected average of 1 week
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2016.
- Derived from this study: PubMed 37870112Eilertsen H, Menon CS, Law ZK, Chen C, Bath PM, Steiner T, Desborough MJ, Sandset EC, Sprigg N, Al-Shahi Salman R. Haemostatic therapies for stroke due to acute, spontaneous intracerebral haemorrhage. Cochrane Database Syst Rev. 2023 Oct 23;10(10):CD005951. doi: 10.1002/14651858.CD005951.pub5.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Four Factor Prothrombin Complex Concentrate and Fresh Frozen Plasma in people with Intracranial Hemorrhage, Traumatic and Intracranial Hemorrhage, Spontaneous, run by University of Utah at 1 site in United States.
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 3 inclusion and 7 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: withdrawn, as of the sponsor's last update on 16 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Rapid reversal of warfarin as measured by international normalized ratio (INR) drawn at 30 minutes after transfusion (time frame: 30 minutes after transfusion completion). 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 NCT02429453, which also lists 1 linked publication.
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 16 Nov 2016.