an open-label, randomized, multicenter phase iiib study to assess the efficacy, safety and tolerance of beriplex® p/n (kcentra) compared with plasma for rapid reversal of coagulopathy induced by vitamin k antagonists in subjects requiring an urgent surgical procedure

Conditions: Reversal of Coagulopathy

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 vitamin k antagonists in subjects who require immediate correction of international normalized ratio (inr) because of emergency surgery.


Eligibility criteria:
inclusion criteria: * male and female subjects greater than or equal to 18 years, * subjects currently on oral vitamin k antagonist (vka) therapy, * an urgent surgical procedure is required within 24 hours of the start of investigational medicinal product (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

Keywords: anticoagulant reversal prothrombin complex concentrate coagulopathy coumarin derivatives emergency surgery invasive procedures vitamin k reversal of coagulopathy induced by coumarin derivatives kcentra