Efficacy and Safety of 4F-PCC (4-Factor Prothrombin Complex Concentrate) in Adult Patients Undergoing Complex Cardiovascular Surgery With Cardiopulmonary Bypass (CPB)

Number of Participants With Effective or Not Effective Hemostatic Response from 30 Minutes to 24 Hours After the End of IP Infusion

The hemostatic response will be recorded as either effective or not effective. 'Effective' is defined as no hemostatic intervention was required, whereas 'non effective' is defined as a hemostatic intervention was required in the period from 30 minutes to 24 hours after the end of IP infusion. Hemostatic intervention includes surgical re-intervention for bleeding and / or the administration of any systemic hemostatic agents.

Time frame: Up to 24 hours after the end of IP infusion

Number of Participants With and Without Successful Correction of Coagulation Factor Deficiency

Successful correction ("Yes or No") of coagulation factor deficiency measured by a rotational thromboelastometry (ROTEM) extrinsically activated thromboelastometric test (EXTEM) clotting time (CT) ≤ 80 seconds or thromboelastography (TEG) reaction time ≤ 8 minutes. ROTEM and TEG are viscoelastic coagulation tests that quantify the process of clot formation and degradation.

Time frame: At Day 1 after IP infusion (30 minutes after the end of infusion)

Change in INR from Baseline

Time frame: From baseline (before IP infusion), to 30 minutes, 6 hours, 24 hours, and 48 hours after the end IP infusion

Number of Participants With Effective and Not Effective Hemostatic Response From the Start of IP Infusion to 24 Hours After the Start of IP Infusion

The hemostatic response will be recorded as either effective or not effective. 'Effective' is defined as no hemostatic intervention was required, whereas 'non effective' is defined as a hemostatic intervention was required in the period from the start of IP infusion to 24 hours after the start of IP infusion. Hemostatic intervention includes surgical re-intervention for bleeding and / or the administration of any systemic hemostatic agents.

Time frame: Up to 24 hours after the start of IP infusion

Change in Z-Scores for ROTEM EXTEM CT and TEG Reaction Time

Measurements on either ROTEM EXTEM CT or TEG reaction time will be collected. To combine these measurements, z-scores will be calculated for each method of measurement. The z-score standardizes each measurement by subtracting the mean and dividing by the standard deviation of the respective method.

Time frame: From baseline (before IP infusion) to 30 minutes and 24 hours after the end IP infusion

Change in Bleeding Severity Scale (BSS) Score From Baseline

The BSS is a validated intraoperative scale used in clinical studies of hemostatic agents as a measure of bleeding severity. Bleeding is scored on a scale from 0 (no bleeding) to 4 (unidentified or inaccessible spurting or gush). A lower score indicates a better outcome.

Time frame: From baseline (before IP infusion) to 30 minutes after end of IP infusion

Number of Participants in Each Universal Definition for Perioperative Bleeding (UDPB) Class

Bleeding is assessed based on 9 events occurring during surgery or within the first postoperative day. These 9 events will be used to determine UDPB class ranging from Class 0 to 5 as follows: Class 0 (insignificant), Class 1 (mild), Class 2 (moderate), Class 3 (severe), and Class 4 (massive).

Time frame: During surgery (Day 1) and on the first postoperative day (Day 2)

Total Number of Units of Allogeneic Blood Products (ABPs) Administered

The ABPs include whole blood, cryoprecipitate, platelets, red blood cells (RBCs), and FFP (except the dose administered as IP). For the purposes of this study, a dose of fibrinogen concentrate will be counted as an ABP, because it is administered in lieu of cryoprecipitate.

Time frame: From the start of IP infusion and up to 24 hours and 5 days after surgery

Number of Units of Individual ABPs Administered

The ABPs include whole blood, cryoprecipitate, platelets, RBCs, and FFP (except the dose administered as IP). For the purposes of this study, a dose of fibrinogen concentrate will be counted as an ABP, because it is administered in lieu of cryoprecipitate.

Time frame: Up to 24 hours after the start of IP infusion

Volume of Chest Tube Output

Time frame: Up to 24 hours after the end of surgery

Number of Participants Requiring Reoperation for Bleeding and for Other Reasons

Time frame: Up to 30 days after surgery

Duration of Mechanical Ventilation

The duration of mechanical ventilation is defined as the number of days on mechanical ventilation after the study surgery. If there are multiple incidences of mechanical ventilation, the duration will be the sum of the number of days for all incidences.

Time frame: Up to 30 days after surgery

Duration of Primary Intensive Care Unit (ICU) Stay

The duration of primary ICU stay is defined as the number of days in the ICU after the study surgery.

Time frame: Up to 30 days after surgery

Duration of Primary Hospital Stay

The duration of primary hospital stay is defined as the duration in calendar days from the date of IP administration to the date of primary hospital discharge, or death in the hospital, or end of study (EOS) visit, whichever occurs first.

Time frame: Up to 30 days after surgery

Number of Deaths

Time frame: Up to Day 1 during the primary hospital stay, and within 28 days following IP infusion

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs)

Time frame: Up to 30 days after IP infusion

Change in Plasma Concentrations of Coagulation Factor II (FII), Factor VII (FVII), Factor IX (FIX), and Factor X (FX), and Proteins C and S From Baseline

Time frame: From baseline to 30 minutes after the end of IP infusion

Plasma Concentrations of Coagulation FII, FVII, FIX, and FX and Proteins C and S

Time frame: Up to 48 hours after the end of IP infusion