An Open-label, Randomized, Multicenter Phase IIIb Study to Assess the Efficacy, Safety and Tolerance of BERIPLEX® P/N Compared With Plasma for Rapid Reversal of Coagulopathy Induced by Vitamin K Antagonists in Subjects Requiring an Urgent Surgical Procedure (BE1116_3003)

Inclusion Criteria:

• Male and female subjects greater than or equal to 18 years,
• Subjects currently on oral VKA therapy,
• An urgent surgical procedure is required within 24 hours of the start of IMP,
• Due to the nature of the procedure, withdrawal of oral VKA therapy and infusion of plasma are also indicated to reverse the VKA effect,
• INR greater than or equal to 2 within 3 hours before start of IMP,
• Informed consent has been obtained.

Exclusion Criteria:

• Subjects requiring urgent surgical procedures where according to the surgeon's clinical judgment, an accurate estimate of blood loss is not possible (e.g., ruptured aneurysm),
• Subjects for whom administration of intravenous vitamin K and vitamin K antagonists withdrawal alone can adequately correct the subject's coagulopathy before initiation of the urgent surgical procedure,
• Administration of intravenous vitamin K more than 3 hours or administration of oral vitamin K more than 6 hours prior to infusion of IMP,
• Subjects in whom lowering INR within normal range may present an unacceptable risk for a thromboembolic complication where the INR goal is to lower but not normalize the INR because of risk of a procedure-associated stroke,
• Subjects, who despite medical management that includes close monitoring and diuretics, may not, by investigator assessment, tolerate the total volume of IMP required by the protocol,
• Expected need for additional non-study blood products before infusion of IMP (Note: Administration of packed red blood cells is not an exclusion criterion),
• Expected need for platelet transfusions or desmopressin before Day 10,
• Acute trauma for which reversal of vitamin K antagonists alone would not be expected to control or resolve an acute bleeding complication and/or control the acute bleeding event,
• Unfractionated or low molecular weight heparin use within 24 hours before randomization or potential need before completion of the procedure,
• History of thromboembolic event, myocardial infarction, unstable angina pectoris, critical aortic stenosis, cerebral vascular accident, transient ischemic attack, severe peripheral vascular disease, disseminated intravascular coagulation within 3 months of enrollment,
• Reversal of VKA therapy alone may not resolve the coagulopathy (eg, receiving a potent anti-platelet agent, i.e., clopidogrel or prasugrel, or advanced liver disease),
• Known history of antiphospholipid antibody syndrome or lupus anticoagulant antibodies,
• Suspected or confirmed serious viral or bacterial infection, e.g., meningitis, or sepsis at time of enrollment,
• Administration of whole blood, plasma, plasma fractions or platelets within 2 weeks prior to inclusion into the study (Note: Administration of packed red blood cells is not an exclusion criterion),
• Pre-existing progressive fatal disease with a life expectancy of less than 2 months,
• Known inhibitors to coagulation factors II, VII, IX, or X; or hereditary protein C or protein S deficiency; or heparin-induced, type II thrombocytopenia,
• Treatment with any other investigational medicinal product within 30 days prior to inclusion into the study,
• Presence or history of hypersensitivity to components of the study medication,
• Pregnant or breast-feeding women,
• Prior inclusion in this study or any other CSL Behring sponsored Beriplex study,
• For subjects with intracranial hemorrhage with:
• Glasgow Coma Score <10 (see Appendix 8)
• modified Rankin Score > 3 prior to ICH (see Appendix 9)
• Intracerebral hemorrhage
• Epidural hematomas
• Infratentorial hemorrhage
• Subarachnoid hemorrhage (SAH) subjects with a Hunt and Hess Scale >2
• Subdural hematomas that:
• are judged to be an acute subdural hematoma (based on neurosurgeon review)
• have a concurrent SAH or parenchymal contusion