Phase 3 Study on the Efficacy and Safety of Human Plasma Derived Antithrombin (Atenativ) in Heparin-Resistant Patients Scheduled to Undergo Cardiac Surgery Necessitating Cardiopulmonary Bypass

Inclusion Criteria

• Planned cardiac surgery with CPB
• Heparin-resistant patients (pre-CPB Hemochron ACT less than 480 s in the measurement taken between 2-5 minutes following intravenous administration of 500 U/kg UFH)
• Patients between 18 and 85 years of age, inclusive
• Freely given written or electronic informed consent
• In female patients of childbearing potential, a pre-existing negative pregnancy test within 14 days prior to surgery

Exclusion Criteria

• Receiving, or have received within the timeframes specified, one or more of the following medications prior to the start of surgery:

• vitamin K antagonists (within 3 days)
• direct oral anticoagulants (within 2 days)
• thienopyridines (ticlopidine within 14 days, prasugrel within 7 days, or clopidogrel within 5 days), unless platelet function is satisfactory according to local standard of care assessment
• ticagrelor (within 5 days), unless platelet function is satisfactory according to local standard of care assessment
• glycoprotein IIb/IIIa antagonist (within 24 hours)
• Pre-existing coagulopathy, a history of bleeding problems, or a laboratory-diagnosed bleeding disorder (e.g., von Willebrand disease, platelet disorder)
• Renal insufficiency, defined as serum creatinine level >2.0 mg/dL
• Thrombocytosis, defined as platelet count >400,000 per μL
• Known hypersensitivity or allergic reaction to antithrombin or any of the excipients in Atenativ, i.e., human albumin, sodium chloride, acetyl tryptophan, caprylic acid
• History of anaphylactic reaction(s) to blood or blood components
• Refusal to receive transfusion of blood or blood-derived products
• Current participation in another interventional clinical trial or previous participation in the current trial
• Treatment with any IMP within 30 days prior to screening visit