Efficacy and Safety Study of BERIPLEX® P/N (Kcentra) Compared With Plasma in Patients With Acute Major Bleeding Caused by Anticoagulant Therapy
Condition: Blood Coagulation Disorders; Acute Major Bleeding
MeSH terms: Hemostatic Disorders; Blood Coagulation Disorders; Hemorrhage
Intervention: Beriplex® P/N (Kcentra); Fresh frozen plasma
Intervention description: Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body weight; Intravenous Infusion, dosage depending on baseline INR and body weight
Intervention MeSH terms: Protein C; Protein S
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 216.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Anticoagulant reversal; Prothrombin; Complex; Concentrate; Coagulopathy; induced by; coumarin; derivatives; Kcentra

Summary:

      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.
    

Eligibility criteria:

        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