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

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 Coumarin Derivatives in Subjects With Acute Major Bleeding

The purpose of this study is to evaluate efficacy, safety and tolerance of BERIPLEX® P/N (Kcentra) compared with plasma in regard to rapid reversal of coagulopathy induced by coumarin derivatives in subjects who require immediate correction of INR (International Normalized Ratio)and to stop an acute major bleeding.

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