Efficacy and Safety Study of BERIPLEX® P/N (Kcentra) Compared With Plasma in Patients With Acute Major Bleeding Caused by Anticoagulant Therapy

Inclusion criteria

• Male and female subjects ≥ 18 years
• Subjects who have received oral vitamin K-antagonist therapy
• Subjects who have acute major bleeding, defined as one of the following: life-threatening or potentially life-threatening, acute bleeding associated with a fall in hemoglobin (Hb) level ≥ 2g/dL, bleeding requiring blood product transfusion
• INR ≥ 2 within 3 hours before start of study treatment
• Informed consent has been obtained

Exclusion criteria

• Expected survival of less than 3 days, or expected surgery in less than 1 day
• Acute trauma for which reversal of vitamin K antagonists alone would not be expected to control the acute bleeding event
• Use of unfractionated or low molecular weight heparin use from 24 hours prior to enrollment or expected need within 24 hours after start of infusion
• For patients with ICH: Glasgow coma score (GCS) < 7; intracerebral hematoma volume > 30cc as assessed by ABC/21; for subdural hematomas: maximum thickness ≥ 10 mm, midline shift ≥ 5 mm; for subarachnoid hemorrhage: any evidence of hydrocephalus; infratentorial ICH location; epidural hematomas; intraventricular extension of hemorrhage; modified Rankin score (mRS) of >3 prior to ICH
• History of thrombotic event, myocardial infarction, disseminated intravascular coagulation, cerebral vascular accident, transient ischemic attack, unstable angina pectoris, or severe peripheral vascular disease within 3 months of enrollment
• Known history of antiphospholipid antibody syndrome or lupus anticoagulant antibodies
• Suspected or confirmed sepsis at time of enrollment
• Administration of whole blood, plasma, plasma fractions or platelets within 2 weeks prior to inclusion into the study
• Large blood vessel rupture (e.g. in advanced cancer patient)
• 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