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.

A Phase III, Randomized, Double-blind, Multicenter Study to Assess the Efficacy and Safety of OCTAPLEX, a Four-factor Prothrombin Complex Concentrate (4F-PCC), Compared to the 4F-PCC Beriplex® P/N (Kcentra), for the Reversal of Vitamin K Antagonist (VKA) Induced Anticoagulation in Patients Needing Urgent Surgery With Significant Bleeding Risk.

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).

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

The secondary objective of the study is to investigate the safety and tolerability of OCTAPLEX compared to Beriplex® P/N (Kcentra) in patients under Vitamin K Antagonist (VKA) therapy with the need for urgent surgery with significant bleeding risk.

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.