FFP Versus PCC in Intracranial Hemorrhage

Not Applicable

Withdrawn

• Conditions: Intracranial Hemorrhage, Spontaneous; Intracranial Hemorrhage, Traumatic
• Interventions: Biological: Fresh Frozen Plasma; Drug: Four Factor Prothrombin Complex Concentrate

• Registration Number: NCT02429453
• Lead Sponsor: University of Utah

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2015-04
• Study First Submitted: 2015-04-21
• Study First Submitted QC: 2015-04-23
• Study First Posted: 2015-04-29
• Primary Completion: 2016-03
• Study Completion: 2016-03
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-15
• Last Update Posted: 2016-11-16

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fresh Frozen Plasma	Fresh Frozen Plasma	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+
Four Factor Prothrombin Complex Concentrate	Four Factor Prothrombin Complex Concentrate	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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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%
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
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
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
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
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
In hospital mortality	During duration of hospital stay, an expected average of 1 week	Mortality during hospital stay
Total hospital cost	During duration of hospital stay, an expected average of 1 week	Total cost of hospital stay based on hospital charges
30 day outcome as measured by the Glasgow outcome score	30 days after discharge	Glasgow outcome score 30 days after discharge
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

Trial Locations

Locations (1)

University of Utah Medical Center; 🇺🇸 Salt Lake City, Utah, United States