FFP Versus PCC in Intracranial Hemorrhage

Intracranial Hemorrhage, Traumatic Clinical Trial

Official title:

Fresh Frozen Plasma Versus Four Factor Prothrombin Complex Concentrate for Reversal of Vitamin K Antagonists in Intracranial Hemorrhage

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02429453
• Other study ID #: IRB_00078143
• Status: Withdrawn
• Phase: N/A
• First received: April 21, 2015
• Last updated: November 15, 2016
• Start date: April 2015
• Est. completion date: March 2016

Study information

• Verified date: November 2016
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemorrhage
• Intracranial Hemorrhage, Spontaneous
• Intracranial Hemorrhage, Traumatic
• Intracranial Hemorrhages

Intervention

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

Biological:
• Fresh Frozen Plasma
A pooled collection of plasma from donors

Locations

Country	Name	City	State
United States	University of Utah Medical Center	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
University of Utah

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	30 minutes after transfusion completion	No
Secondary	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%	24 hours after presentation	No
Secondary	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	3-24 hours after completion of FFP or 4 factor prothrombin complex concentrate transfusion	No
Secondary	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	30 minutes and 24 hours after completion of FFP or 4 factor prothrombin complex concentrate transfusion	No
Secondary	Absolute INR reversal as measured by INR drawn 24 hours after transfusion	Difference between initial INR and INR 24 hours after completion of transfusion	24 hours after completion of FFP or 4 factor prothrombin complex concentrate transfusion	No
Secondary	Need for operative intervention as measured by need for neurosurgical procedure during the hospitalization	Need for operative intervention during hospitalization related to initial trauma	During duration of hospital stay, an expected average of 1 week	No
Secondary	Estimated blood loss during any neurosurgical procedure	Estimated blood loss during any neurosurgical interventions during the hospitalization	During duration of hospital stay, an expected average of 1 week	No
Secondary	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	During duration of hospital stay, an expected average of 1 week	No
Secondary	In hospital mortality	Mortality during hospital stay	During duration of hospital stay, an expected average of 1 week	No
Secondary	Total hospital cost	Total cost of hospital stay based on hospital charges	During duration of hospital stay, an expected average of 1 week	No
Secondary	30 day outcome as measured by the Glasgow outcome score	Glasgow outcome score 30 days after discharge	30 days after discharge	No
Secondary	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	During duration of hospital stay, an expected average of 1 week	No