Clinical Trial: Factor VII, Prothrombin Complex Concentrate, and Fresh Frozen Plasma in Warfarin-Related Intracranial Hemorrhage

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Comparison of Recombinant Activated Factor VII, Prothrombin Complex Concentrate, and Fresh Frozen Plasma for Anticoagulation Reversal in Warfarin-Associated Acute Intracranial

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 Summary:

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 pro
Sponsor: University of Utah

Current Primary Outcome: Normalization of INR (<1.4) [ Time Frame: 20min, 2hrs, 4hrs, 6hrs, 24hrs ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Hematoma progression [ Time Frame: 24hrs ]
  • Neurological status [ Time Frame: 24hrs & 1month ]
  • Timing of intervention completion [ Time Frame: 24hrs ]
  • Dosing of intervention required [ Time Frame: 24hrs ]
  • Medical complications during hospitalization [ Time Frame: days ]


Original Secondary Outcome: Same as current

Information By: University of Utah

Dates:
Date Received: October 9, 2008
Date Started: April 2008
Date Completion:
Last Updated: November 22, 2011
Last Verified: November 2011