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FFP Versus PCC in Intracranial Hemorrhage

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ClinicalTrials.gov Identifier: NCT02429453
Recruitment Status : Withdrawn (Lack of enrolment)
First Posted : April 29, 2015
Last Update Posted : November 16, 2016
Sponsor:
Information provided by (Responsible Party):
Jian Guan, 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.

Condition or disease Intervention/treatment Phase
Intracranial Hemorrhage, Traumatic Intracranial Hemorrhage, Spontaneous Drug: Four Factor Prothrombin Complex Concentrate Biological: Fresh Frozen Plasma Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Fresh Frozen Plasma Versus Four Factor Prothrombin Complex Concentrate for Reversal of Vitamin K Antagonists in Intracranial Hemorrhage
Study Start Date : April 2015
Actual Primary Completion Date : March 2016
Actual Study Completion Date : March 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding

Arm Intervention/treatment
Active Comparator: 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+
Biological: Fresh Frozen Plasma
A pooled collection of plasma from donors

Experimental: 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
Drug: Four Factor Prothrombin Complex Concentrate
A purified, non-activated prothrombin complex concentrate containing factors II, VII, IX and X and proteins C & S
Other Name: Kcentra




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Radiographic expansion of traumatic intracerebral hemorrhage as measured by CT scan within 24 hours of presentation [ Time Frame: 24 hours after presentation ]
    Expansion of blood on repeat CT scan of >10%

  2. 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 ]
    INR level at 3 hours, 8 hours and 24 hours after transfusion completion of FFP or prothrombin complex concentrate

  3. 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 ]
    Results of ROTEM analysis at 30 minutes and 24 hours after transfusion

  4. 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 ]
    Difference between initial INR and INR 24 hours after completion of transfusion

  5. 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 ]
    Need for operative intervention during hospitalization related to initial trauma

  6. Estimated blood loss during any neurosurgical procedure [ Time Frame: During duration of hospital stay, an expected average of 1 week ]
    Estimated blood loss during any neurosurgical interventions during the hospitalization

  7. 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 ]
    Need for blood product transfusions during hospitalization

  8. In hospital mortality [ Time Frame: During duration of hospital stay, an expected average of 1 week ]
    Mortality during hospital stay

  9. Total hospital cost [ Time Frame: During duration of hospital stay, an expected average of 1 week ]
    Total cost of hospital stay based on hospital charges

  10. 30 day outcome as measured by the Glasgow outcome score [ Time Frame: 30 days after discharge ]
    Glasgow outcome score 30 days after discharge

  11. 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 ]
    Development of deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, unanticipated intubation, heart failure, or need for aggressive diuresis



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02429453


Locations
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United States, Utah
University of Utah Medical Center
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
University of Utah

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Responsible Party: Jian Guan, Neurosurgery Resident, University of Utah
ClinicalTrials.gov Identifier: NCT02429453     History of Changes
Other Study ID Numbers: IRB_00078143
First Posted: April 29, 2015    Key Record Dates
Last Update Posted: November 16, 2016
Last Verified: November 2016
Keywords provided by Jian Guan, University of Utah:
Warfarin
Traumatic intracranial hemorrhage
prothrombin complex concentrate
fresh frozen plasma
Spontaneous intracranial hemorrhage
Additional relevant MeSH terms:
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Intracranial Hemorrhages
Intracranial Hemorrhage, Traumatic
Hemorrhage
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Thrombin
Hemostatics
Coagulants