Fresh Frozen Plasma Versus Four Factor Prothrombin Complex Concentrate for Reversal of Vitamin K Antagonists in Intracranial Hemorrhage
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Rapid reversal of warfarin as measured by international normalized ratio (INR) drawn at 30 minutes after transfusion
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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+
干预措施: Fresh Frozen Plasma (Biological)
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
干预措施: Four Factor Prothrombin Complex Concentrate (Drug)
结局指标
主要结局
Rapid reversal of warfarin as measured by international normalized ratio (INR) drawn at 30 minutes after transfusion
时间窗: 30 minutes after transfusion completion
INR level 30 minutes after transfusion completion of FFP or 4 factor prothrombin complex concentrate
次要结局
- Radiographic expansion of traumatic intracerebral hemorrhage as measured by CT scan within 24 hours of presentation(24 hours after presentation)
- 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)
- 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)
- 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)
- Estimated blood loss during any neurosurgical procedure(During duration of hospital stay, an expected average of 1 week)
- 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)
- 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)
- In hospital mortality(During duration of hospital stay, an expected average of 1 week)
- Total hospital cost(During duration of hospital stay, an expected average of 1 week)
- 30 day outcome as measured by the 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)
研究者
Jian Guan
Neurosurgery Resident
University of Utah