Safety and Efficacy of Preoperative Antithrombin Supplementation in Patients Undergoing High-Risk Cardiopulmonary Bypass

Inclusion Criteria

• Male or female.
• At least 18 years of age.
• Subject needed non-emergency cardiac surgery with CPB.
• Types of cardiac operations permitted: complex/combined procedures (CABG+valve), double/triple valve repair/replacement, ascending aorta/aortic arch surgeries. Isolated CABG or single valve repair/replacements were allowed only if subject had received preoperative heparin >2 days.
• Following the incorporation of Protocol Version 4.0 (Amendment 3 dated 02 Apr 2015), this criterion was revised to include complex/combined procedures (CABG+valve), double/triple valve repair/replacements, ascending aorta/aortic arch surgeries (without baseline AT level restriction or preoperative heparin requirement). OR isolated CABG or single valve repair/replacements were allowed only if either (a) AT level was less than 80% OR (b) preoperative heparin was received ([UFH for at least 12 hours; LMWH for more than 5 days).
• Subject had a baseline AT level of less than 80%.
• Following incorporation of Protocol Version 3.0 (Amendment 2 dated 02 Sep 2014) this was changed to Subject had a Prescreening/Screening and baseline local lab AT level of less than 80%.
• Following the incorporation of Protocol Version 4.0 (Amendment 3 dated 02 Apr 2015) this criterion was deleted and noted as "Not applicable - intentionally left blank for data management purposes (consistency in eCRF capture of eligibility criteria historically)."
• Subject had signed informed consent form.
• Subject was willing to comply with all aspects of the protocol, including blood sampling, for the total duration of the study.

Exclusion Criteria

• Subject needed emergency surgery.
• Subject needed heart transplantation.
• Subject needed the use of minimally invasive surgery.
• Subject had previous cardiac operation.
• Subject had infective endocarditis.
• Subject had thromboembolic events, stroke, or ST-elevated MI within 7 days of surgery.
• Subject had cardiogenic shock at the time of surgery.
• Subject had renal dysfunction: creatinine levels >2 mg/dL or chronic dialysis.
• Subject had liver dysfunction: aspartate aminotransferase (AST), alanine aminotransferase (ALT) increase ≥2-fold above the upper-limit of local lab normal ranges.
• Subject had treatment with Clopidogrel® and Ticagrelor® within 5 days before surgery, Prasugrel® within 7 days before surgery, glycoprotein IIb/IIIa receptor blockers within 24 hours of surgery.
• Subject had treatment with new oral anticoagulants (Apixaban®, Rivaroxaban®, Dabigatran®) within 48 hours before surgery.
• Subject had Vitamin K antagonist therapy and an international normalized ratio (INR) >1.3 on the day of surgery.
• Subject had platelet count <120,000/μL.
• Subject had history or suspicion of a congenital or acquired coagulation disorder.
• Subject had history of anaphylactic reaction(s) to blood or blood components.
• Subject had allergies to excipients in the study drug.
• Subject had refused to receive allogenic transfusion of blood-derived products.
• Subject had received AT treatment within the last 3 months prior to Screening Visit.
• Subject was pregnant. Subject had participated in any another investigational study within the last 3 months prior to Screening Visit.