Clinical trial NCT00770718: Factor VII, Prothrombin Complex Concentrate, and Fresh Frozen Plasma in Warfarin-Related Intracranial Hemorrhage
Official title: A Comparison of Recombinant Activated Factor VII, Prothrombin Complex Concentrate, and Fresh Frozen Plasma for Anticoagulation Reversal in Warfarin-Associated Acute Intracranial Hemorrhage: A Dose Ranging Pilot Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Intracranial Hemorrhage
Keywords: intracranial hemorrhage
warfarin
anticoagulant
Factor VII
Prothrombin
Lead sponsor: University of Utah
Sponsor class: OTHER
Collaborators: name: Sheila B. Terry Memorial Research Fund
First posted: 2008-10-10
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this dose-ranging pilot study is to compare Recombinant Activated Factor VII, Prothrombin Complex Concentrate and Fresh Frozen Plasma (each starting at low doses with escalation if necessary) for the reversal of warfarin in the setting of acute intracranial hemorrhage.

Detailed description: Both recombinant activated Factor VIIa (rFVIIa) as well as Prothrombin Complex Concentrate (PCC) are labeled for the treatment of bleeding episodes in patients with hemophilia. Many hospitals are also using each for the following unlabeled indications: bleeding rescue in surgical patients, severe multiple trauma with ongoing bleeding, intracranial bleeding \< 4 hours since symptom onset, traumatic head injury with evidence of expanding bleed, retroperitoneal bleed, and life-threatening bleeding due to idiopathic coagulopathy. To our knowledge, these two products have never been clinically compared head to head for the reversal of warfarin in the setting of intracranial hemorrhage.

The rFVIIa (Novoseven) guidelines are based off of national data and utilize a dose range of 40-90 mcg/kg of ideal body weight (2.8-6.3 mg for a 70 kg. patient) with an additional dose if needed. The dose cited in the literature for the management of intracerebral bleeds ranges from 10 to 120 mcg/kg (0.7 - 8.4 mg for a 70 kg. patient,) with higher doses associated with increased risk of thromboembolic events.

The recommended dosing of PCC is 30-50 i.u. per kilogram of ideal body weight with additional dosing if needed. PCC (Profilnine®SD) is a mixture of the following vitamin K-dependent clotting factors: II (prothrombin), VII (proconvertin), IX (plasma thromboplastin component; PTC; Christmas factor), and X (Stuart-Prower factor). These factors are required for the conversion of prothrombin to thrombin and thus adequate hemostasis, and are synthesized in the liver.

Currently at the most hospitals around the country, fresh frozen plasma (FFP) is the mainstay for reversal of warfarin-related coagulopathy in intracranial hemorrhage at the discretion of the treating attending physician. We propose to study all the current reversal practices in the intracranial hemorrhage population here at the University of Utah as part of a quality improvement project for both patient safety and cost.

We will perform a safety and feasibility study comparing dosage regimens of rFVIIa, FIXa and fresh frozen plasma (FFP) infusion in the normalization of coagulopathy in the context of warfarin-related intracerebral hemorrhage. Our primary outcome is time to INR normalization defined as INR≤ 1.3 on two consecutive readings separated by 2 hours.

Eligibility criteria: Inclusion Criteria:

* Non-traumatic intracranial hemorrhage (subdural or intraparenchymal)
* Known warfarin ingestion
* INR ≥2.0
* GCS \<13

Exclusion Criteria:

* Pregnancy
* History of venous thrombosis or pulmonary embolus
* Acute myocardial infarction
* Acute stroke

Primary outcomes:
measure: Normalization of INR (<1.4)
timeFrame: 20min, 2hrs, 4hrs, 6hrs, 24hrs
Secondary outcomes:
measure: Hematoma progression
timeFrame: 24hrs
measure: Neurological status
timeFrame: 24hrs & 1month
measure: Timing of intervention completion
timeFrame: 24hrs
measure: Dosing of intervention required
timeFrame: 24hrs
measure: Medical complications during hospitalization
timeFrame: days
Other outcomes:
Locations:
Study officials:
References: