Clinical trial NCT02429453: FFP Versus PCC in Intracranial Hemorrhage
Official title: Fresh Frozen Plasma Versus Four Factor Prothrombin Complex Concentrate for Reversal of Vitamin K Antagonists in Intracranial Hemorrhage
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Intracranial Hemorrhage, Traumatic
Intracranial Hemorrhage, Spontaneous
Keywords: Warfarin
Traumatic intracranial hemorrhage
prothrombin complex concentrate
fresh frozen plasma
Spontaneous intracranial hemorrhage
Lead sponsor: University of Utah
Sponsor class: OTHER
First posted: 2015-04-29
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rapid reversal of warfarin as measured by international normalized ratio (INR) drawn at 30 minutes after transfusion
timeFrame: 30 minutes after transfusion completion
Secondary outcomes:
measure: Radiographic expansion of traumatic intracerebral hemorrhage as measured by CT scan within 24 hours of presentation
timeFrame: 24 hours after presentation
measure: Timing of reversal of warfarin as measured by INR drawn at 3 hours, 8 hours and 24 hours after transfusion
timeFrame: 3-24 hours after completion of FFP or 4 factor prothrombin complex concentrate transfusion
measure: Thromboelastography response as measured by results of ROTEM analysis at 30 minutes and 24 hours after transfusion
timeFrame: 30 minutes and 24 hours after completion of FFP or 4 factor prothrombin complex concentrate transfusion
measure: Absolute INR reversal as measured by INR drawn 24 hours after transfusion
timeFrame: 24 hours after completion of FFP or 4 factor prothrombin complex concentrate transfusion
measure: Need for operative intervention as measured by need for neurosurgical procedure during the hospitalization
timeFrame: During duration of hospital stay, an expected average of 1 week
measure: Estimated blood loss during any neurosurgical procedure
timeFrame: During duration of hospital stay, an expected average of 1 week
measure: Further transfusion needs as measured by number of units of blood/platelet/plasma products transfused during the hospitalization
timeFrame: During duration of hospital stay, an expected average of 1 week
measure: In hospital mortality
timeFrame: During duration of hospital stay, an expected average of 1 week
measure: Total hospital cost
timeFrame: During duration of hospital stay, an expected average of 1 week
measure: 30 day outcome as measured by the Glasgow outcome score
timeFrame: 30 days after discharge
measure: 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
timeFrame: During duration of hospital stay, an expected average of 1 week
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
Study officials:
References: