Clinical Trial: FFP Versus PCC in Intracranial Hemorrhage

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

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

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 Summary:

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 intracr
Sponsor: University of Utah

Current Primary Outcome: 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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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%
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • In hospital mortality [ Time Frame: During duration of hospital stay, an expected average of 1 week ]
    Mortality during hospital stay
  • 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
  • 30 day outcome as measured by the Glasgow outcome score [ Time Frame: 30 days after discharge ]
    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 [ 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


Original Secondary Outcome:

  • 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%
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • In hospital mortality [ Time Frame: During duration of hospital stay, an expected average of 1 week ]
    Mortality during hospital stay
  • 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
  • 30 day outcome as measured by the Glasgow outcome score [ Time Frame: 30 days after discharge ]
    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 [ Time Frame: During duration of hospital stay, an expected average of 1 week ]
    Development of deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, unantincipated intubation, heart failure, or need for aggressive diuresis


Information By: University of Utah

Dates:
Date Received: April 21, 2015
Date Started: April 2015
Date Completion:
Last Updated: November 15, 2016
Last Verified: November 2016