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FFP Versus PCC in Intracranial Hemorrhage

Primary Purpose

Intracranial Hemorrhage, Traumatic, Intracranial Hemorrhage, Spontaneous

Status
Withdrawn
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Four Factor Prothrombin Complex Concentrate
Fresh Frozen Plasma
Sponsored by
University of Utah
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Intracranial Hemorrhage, Traumatic focused on measuring Warfarin, Traumatic intracranial hemorrhage, prothrombin complex concentrate, fresh frozen plasma, Spontaneous intracranial hemorrhage

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Utah Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Fresh Frozen Plasma

Four Factor Prothrombin Complex Concentrate

Arm Description

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+

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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%
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
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
Absolute INR reversal as measured by INR drawn 24 hours after 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
Need for operative intervention during hospitalization related to initial trauma
Estimated blood loss during any neurosurgical procedure
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
Need for blood product transfusions during hospitalization
In hospital mortality
Mortality during hospital stay
Total hospital cost
Total cost of hospital stay based on hospital charges
30 day outcome as measured by the Glasgow outcome score
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
Development of deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, unanticipated intubation, heart failure, or need for aggressive diuresis

Full Information

First Posted
April 21, 2015
Last Updated
November 15, 2016
Sponsor
University of Utah
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1. Study Identification

Unique Protocol Identification Number
NCT02429453
Brief Title
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

2. Study Status

Record Verification Date
November 2016
Overall Recruitment Status
Withdrawn
Why Stopped
Lack of enrolment
Study Start Date
April 2015 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Utah

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intracranial Hemorrhage, Traumatic, Intracranial Hemorrhage, Spontaneous
Keywords
Warfarin, Traumatic intracranial hemorrhage, prothrombin complex concentrate, fresh frozen plasma, Spontaneous intracranial hemorrhage

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fresh Frozen Plasma
Arm Type
Active Comparator
Arm Description
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+
Arm Title
Four Factor Prothrombin Complex Concentrate
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Four Factor Prothrombin Complex Concentrate
Other Intervention Name(s)
Kcentra
Intervention Description
A purified, non-activated prothrombin complex concentrate containing factors II, VII, IX and X and proteins C & S
Intervention Type
Biological
Intervention Name(s)
Fresh Frozen Plasma
Intervention Description
A pooled collection of plasma from donors
Primary Outcome Measure Information:
Title
Rapid reversal of warfarin as measured by international normalized ratio (INR) drawn at 30 minutes after transfusion
Description
INR level 30 minutes after transfusion completion of FFP or 4 factor prothrombin complex concentrate
Time Frame
30 minutes after transfusion completion
Secondary Outcome Measure Information:
Title
Radiographic expansion of traumatic intracerebral hemorrhage as measured by CT scan within 24 hours of presentation
Description
Expansion of blood on repeat CT scan of >10%
Time Frame
24 hours after presentation
Title
Timing of reversal of warfarin as measured by INR drawn at 3 hours, 8 hours and 24 hours after transfusion
Description
INR level at 3 hours, 8 hours and 24 hours after transfusion completion of FFP or prothrombin complex concentrate
Time Frame
3-24 hours after completion of FFP or 4 factor prothrombin complex concentrate transfusion
Title
Thromboelastography response as measured by results of ROTEM analysis at 30 minutes and 24 hours after transfusion
Description
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
Title
Absolute INR reversal as measured by INR drawn 24 hours after transfusion
Description
Difference between initial INR and INR 24 hours after completion of transfusion
Time Frame
24 hours after completion of FFP or 4 factor prothrombin complex concentrate transfusion
Title
Need for operative intervention as measured by need for neurosurgical procedure during the hospitalization
Description
Need for operative intervention during hospitalization related to initial trauma
Time Frame
During duration of hospital stay, an expected average of 1 week
Title
Estimated blood loss during any neurosurgical procedure
Description
Estimated blood loss during any neurosurgical interventions during the hospitalization
Time Frame
During duration of hospital stay, an expected average of 1 week
Title
Further transfusion needs as measured by number of units of blood/platelet/plasma products transfused during the hospitalization
Description
Need for blood product transfusions during hospitalization
Time Frame
During duration of hospital stay, an expected average of 1 week
Title
In hospital mortality
Description
Mortality during hospital stay
Time Frame
During duration of hospital stay, an expected average of 1 week
Title
Total hospital cost
Description
Total cost of hospital stay based on hospital charges
Time Frame
During duration of hospital stay, an expected average of 1 week
Title
30 day outcome as measured by the Glasgow outcome score
Description
Glasgow outcome score 30 days after discharge
Time Frame
30 days after discharge
Title
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
Description
Development of deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, unanticipated intubation, heart failure, or need for aggressive diuresis
Time Frame
During duration of hospital stay, an expected average of 1 week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
University of Utah Medical Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States

12. IPD Sharing Statement

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FFP Versus PCC in Intracranial Hemorrhage

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