Reversibility of Apixaban Anticoagulation With the Four Factor Prothrombin Complex Concentrate Kcentra
Condition: Thrombosis
MeSH terms: Thrombosis
Study type: Interventional
Phase: Phase 1

Summary: 
      Apixaban is an anticoagulant (also known as blood thinner) approved by the Food and Drug
      Administration (FDA) for reducing the risk of stroke and systemic embolism in patients with
      non-valvular atrial fibrillation. It has no reliable method of reversal. Kcentra is an FDA
      approved drug derived from blood that is used as an antidote to treat people with bleeding
      associated with taking the well-known anticoagulant warfarin. This is a Phase I,
      placebo-controlled, single site, open-label, crossover trial to evaluate the reversibility
      apixaban anticoagulation with Kcentra.
    

Detailed description: 
      Oral anticoagulants are effective in the treatment and prevention of venous and arterial
      thrombotic events. For more than 50 years the only class of anticoagulant available had been
      the vitamin K antagonist (VKA), warfarin, which requires frequent blood work for monitoring.
      Apixaban is a new approved anticoagulant that is used to treat patients who have blood clots
      or are at risk for developing blood clots. Unlike warfarin, the use of apixaban does not
      require frequent blood work for monitoring and is associated with lower bleeding risk. All
      anticoagulation therapies are associated with spontaneous or provoked bleeding risk and
      reversal of their blood thinning effects might be needed. Reversal of anticoagulation may
      also be needed in cases where emergent or urgent surgery is indicated. There is currently no
      available reversal agent for apixaban. Prothrombin complex concentrate (PCC) contain clotting
      factors and can replace factors inhibited by anticoagulants. In a recent study in the
      Netherlands a four factor prothrombin complex concentrate, Cofact (not available in the USA)
      was shown to be able to reverse the anticoagulation effects of another factor Xa inhibitor,
      rivaroxaban. Kcentra is a four factor prothrombin complex concentrate that was FDA approved
      in 2013 and is used as an antidote to treat people with bleeding associated with taking
      warfarin. It contains clotting factors II, VII, IX and X derived from donated blood and could
      be effective in reversing the anticoagulation effects of the factor Xa inhibitor, apixaban.
      No effective reversal agent for apixaban exists. Physicians struggle with bleeding in
      patients who are on apixaban. Indeed, this is not an uncommon problem for patients who suffer
      brain bleeds or trauma. This study could potentially identify Kcentra as reversal agent for
      patients taking apixaban. This study will test the hypothesis that Kcentra has the potential
      to significantly reduce the anticoagulation effect of apixaban as measured by thrombin
      generation assay at 30 minutes post infusion of Kcentra as compared to placebo infusion in
      subjects dosed to steady state with apixaban.
    

Intervention name(s): Kcentra; Apixaban; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): IV infusion
Other intervention name(s): 4 factor prothrombin complex concentrate
Intervention MeSH terms: Apixaban
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Xa inhibitor; Prothrombin complex concentrate; anticoagulation