Efficacy and Safety of Prothromplex Total (Prothrombin Complex Concentrate) in Oral Anticoagulant Reversal

An International, Multi-centre, Prospective, Open-Label, Non-Randomised, Uncontrolled Study to Assess the Efficacy and Safety of Prothromplex Total in Oral Anticoagulant Reversal in Patients With Acquired Deficiency of Prothrombin Complex Coagulation Factors (II, VII, IX, X)

The purpose of the study is to assess the efficacy and safety of Prothromplex Total as a treatment for the immediate reversal of oral anticoagulant therapy with vitamin K antagonists in patients with acquired deficiency of prothrombin complex coagulation factors (II, VII, IX, X). Upon enrolment, subjects will receive Prothromplex Total for the treatment of acute bleeding due to oral anticoagulants or for the prevention of excessive bleeding during the interventional procedure (Day 1). Additional doses of Prothromplex Total may be administered at the discretion of the investigator. Efficacy and safety assessments will be performed during a period of 72 (± 4) hours after administration of the last dose of Prothromplex Total or until discharge from hospital, whichever occurs first.

Inclusion Criteria:

• Subject is at least 16 years or older at enrolment with acquired deficiency of prothrombin complex coagulation factors (II, VII, IX, X), due to oral anticoagulation with vitamin K antagonists (e.g. coumarin, warfarin), requiring reversal of oral anticoagulation for urgent surgery, or invasive procedure or acute bleeding episode
• Subject or parent/legally authorised representative has provided written informed consent
• Subject has INR >= 2,0 at screening
• Subject is willing and able to comply with the requirements of the protocol

Exclusion Criteria:

• Subject has laboratory and/or clinical symptoms which are clearly indicative of overt disseminated intravascular coagulation (DIC)
• Subject has been treated with whole blood, fresh frozen plasma (FFP), or platelets within 6 hours prior to study enrolment
• Subject has a hypersensitivity to prothrombin complex concentrate (PCC) constituents (including heparin-induced thrombocytopenia)
• Subject has blood loss of >= 5 units of blood
• Subject has hereditary thrombophilia or bleeding disorder
• Subject has a life expectancy of < 3 months
• Subject has been on oral anticoagulant treatment for a period of < 4 weeks for the treatment of a thrombotic event such as deep vein thrombosis or pulmonary embolism
• Subject has an acute ischemic cardiovascular disorder
• Subject has or is suspected to have sepsis
• Subject with acute or chronic liver failure (hepatic cirrhosis Child-PUGH score C)
• Subject has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to enrolment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study