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

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

The primary objective of this study is to evaluate the efficacy of two different doses of Atenativ, versus placebo, in restoring and maintaining heparin responsiveness in adult patients undergoing cardiac surgery necessitating cardiopulmonary bypass (CPB)

Inclusion Criteria:

1. Planned cardiac surgery with CPB
2. 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)
3. Patients between 18 and 85 years of age, inclusive
4. Freely given written or electronic informed consent
5. In female patients of childbearing potential, a pre-existing negative pregnancy test within 14 days prior to surgery

Exclusion Criteria:

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

   1. vitamin K antagonists (within 3 days)
   2. direct oral anticoagulants (within 2 days)
   3. 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
   4. ticagrelor (within 5 days), unless platelet function is satisfactory according to local standard of care assessment
   5. glycoprotein IIb/IIIa antagonist (within 24 hours)

2. Pre-existing coagulopathy, a history of bleeding problems, or a laboratory-diagnosed bleeding disorder (e.g., von Willebrand disease, platelet disorder)

3. Renal insufficiency, defined as serum creatinine level >2.0 mg/dL

4. Thrombocytosis, defined as platelet count >400,000 per μL

5. Known hypersensitivity or allergic reaction to antithrombin or any of the excipients in Atenativ, i.e., human albumin, sodium chloride, acetyl tryptophan, caprylic acid

6. History of anaphylactic reaction(s) to blood or blood components

7. Refusal to receive transfusion of blood or blood-derived products

8. Current participation in another interventional clinical trial or previous participation in the current trial

9. Treatment with any IMP within 30 days prior to screening visit