Study of Octaplex, a Four-factor Prothrombin Complex Concentrate (4F-PCC) and Beriplex® P/N (Kcentra) for the Reversal of Vitamin K Antagonist (VKA) Induced Anticoagulation in Patients Needing Urgent Surgery With Significant Bleeding Risk.
Condition: Significant Bleeding Risk
MeSH terms: Hemorrhage
Intervention: Octaplex; Beriplex P/N (Kcentra)
Intervention description: OCTAPLEX will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).; Beriplex® P/N (Kcentra) will be administered by intravenous infusion at a rate of 0.12 mL/kg/min (~3 units/kg/min), up to a maximum rate of 8.4 mL/min (~210 units/min).
Intervention MeSH terms: Protein C; Protein S; Thrombin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 208.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: anticoagulant reversal; urgent surgery; invasive procedures; vitamin K; prothrombin complex concentrate; four-factor prothrombin complex concentrate (4F-PCC)

Summary:

      To demonstrate that the efficacy of OCTAPLEX as a reversal agent in patients under Vitamin K
      Antagonist (VKA) therapy with the need for urgent surgery with significant bleeding risk is
      clinically non-inferior to that Beriplex® P/N (Kcentra).
    

Eligibility criteria:

        Inclusion Criteria

          1. Male or female patients at least 18 years of age.

          2. Patients currently on oral anticoagulation treatment with VKA of coumadin or warfarin
             type.

          3. Patients being admitted to the hospital or currently hospitalized where:

               -  an urgent surgery carrying significant bleeding risk (≥50 mL expected blood loss)
                  is required as part of routine clinical care;

               -  the use of oral or parenteral vitamin K alone to reverse anticoagulation is
                  deemed too slow or inappropriate for reversal;

          4. Patients with an international normalized ratio (INR) of 2.0 or above at the time of
             decision to reverse the anticoagulation status.

          5. Patients who have given written informed consent and who are able and willing to
             comply with the procedures described in the study protocol.

        Exclusion Criteria

          1. Patients with a life expectancy of less than 48 hours per physician's judgment (e.g.
             patients with a Glasgow Coma Scale equal to 3 or a Head Abbreviated Injury Score of 6,
             patients requiring continuous inotropic or pressor support, and patients whose status
             is post cardiac arrest).

          2. Patients for whom the planned surgery or procedure is commonly associated with a very
             low bleeding risk (e.g. catheter placement, gastroscopy).

          3. Patients with a history of thromboembolic events (TEEs), myocardial infarction,
             unstable angina pectoris, critical aortic stenosis, cerebrovascular accident,
             transient ischemic attack, severe peripheral vascular disease, or disseminated
             intravascular coagulation within 3 months of enrollment.

          4. Patients with a known congenital bleeding disorder.

          5. Patients with a known antiphospholipid antibody syndrome.

          6. Patients with present or past specific factor inhibitor activity.

          7. Patients with thrombocytopenia of <80,000/μL or history of heparin-induced
             thrombocytopenia.

          8. Patients who have received heparin of any type or any non-VKA anticoagulant within 24
             hours prior to enrollment into the study or with potential need to receive these
             medications before completion of hemostasis evaluation at the end of surgery.

          9. Patients who have received prothrombin complex concentrates (PCCs), fresh frozen
             plasma or vitamin K within 72 hours prior to enrollment into the study.

         10. Patients with a known history of hypersensitivity to plasma-derived products.

         11. Patients with acute major bleeding or polytrauma.

         12. Pregnant or nursing women.

         13. Patients participating in another interventional clinical study currently or during
             the past 30 days prior to enrollment into this study.

         14. Patients previously enrolled in this study.