Intracranial Hemorrhage, Spontaneous, Intracranial Hemorrhage, Traumatic
Conditions
Keywords
Warfarin, Traumatic intracranial hemorrhage, prothrombin complex concentrate, fresh frozen plasma, Spontaneous intracranial hemorrhage
Brief 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 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.
Interventions
A purified, non-activated prothrombin complex concentrate containing factors II, VII, IX and X and proteins C & S
BIOLOGICALFresh Frozen Plasma
A pooled collection of plasma from donors
Sponsors
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rapid reversal of warfarin as measured by international normalized ratio (INR) drawn at 30 minutes after transfusion | 30 minutes after transfusion completion | INR level 30 minutes after transfusion completion of FFP or 4 factor prothrombin complex concentrate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total hospital cost | During duration of hospital stay, an expected average of 1 week | Total cost of hospital stay based on hospital charges |
| Radiographic expansion of traumatic intracerebral hemorrhage as measured by CT scan within 24 hours of presentation | 24 hours after presentation | Expansion of blood on repeat CT scan of \>10% |
| Timing of reversal of warfarin as measured by INR drawn at 3 hours, 8 hours and 24 hours after transfusion | 3-24 hours after completion of FFP or 4 factor prothrombin complex concentrate transfusion | INR level at 3 hours, 8 hours and 24 hours after transfusion completion of FFP or prothrombin complex concentrate |
| Thromboelastography response as measured by results of ROTEM analysis at 30 minutes and 24 hours after transfusion | 30 minutes and 24 hours after completion of FFP or 4 factor prothrombin complex concentrate transfusion | Results of ROTEM analysis at 30 minutes and 24 hours after transfusion |
| Absolute INR reversal as measured by INR drawn 24 hours after transfusion | 24 hours after completion of FFP or 4 factor prothrombin complex concentrate transfusion | Difference between initial INR and INR 24 hours after completion of transfusion |
| In hospital mortality | During duration of hospital stay, an expected average of 1 week | Mortality during hospital stay |
| Estimated blood loss during any neurosurgical procedure | During duration of hospital stay, an expected average of 1 week | Estimated blood loss during any neurosurgical interventions during the hospitalization |
| Further transfusion needs as measured by number of units of blood/platelet/plasma products transfused during the hospitalization | During duration of hospital stay, an expected average of 1 week | Need for blood product transfusions during hospitalization |
| 30 day outcome as measured by the Glasgow outcome score | 30 days after discharge | Glasgow outcome score 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 | During duration of hospital stay, an expected average of 1 week | Development of deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, unanticipated intubation, heart failure, or need for aggressive diuresis |
| Need for operative intervention as measured by need for neurosurgical procedure during the hospitalization | During duration of hospital stay, an expected average of 1 week | Need for operative intervention during hospitalization related to initial trauma |
Countries
United States
Outcome results
None listed