Bleeding Cardiac Surgery Patients
Conditions
Brief summary
This is a multicenter, active-control randomized, prospective, Phase 3 study in adult cardiac surgery patients. 420 patients were randomized at 12 hospitals.
Detailed description
Patients were randomized to receive either 4-factor PCC (Octaplex) or frozen plasma (FP). The study compared the hemostatic treatment response to Octaplex versus FP, defined as effective if no additional systemic or surgical hemostatic intervention is required from 60 minutes to 24 hours after initiation of the first treatment dose. The study includes adult (≥18 years old) patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) and required coagulation factor replacement due to bleeding post-CPB and after adequate reversal of heparin with protamine (as assessed by the surgical staff based on clinical and laboratory criteria) during surgery, and who have a known (e.g., as indicated by INR) or suspected coagulation factor deficiency.
Interventions
DRUGOctaplex
Prothrombin complex concentrate
If additional treatment is required after the maximum dose of IMP is administered or the treatment period has elapsed, patients in both groups will receive frozen plasma
Sponsors
Octapharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Given the physical differences in the products and the emergency nature of the intervention, attending clinicians present during the infusion of the blood products/components were not blinded to the treatment. To minimize bias, treating clinicians were blinded to group assignments until immediately prior to IMP infusion. The sponsor and data management teams were also blinded to treatment group allocations
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult (≥18 years old) patients undergoing any index cardiac surgery employing CPB 2. Coagulation factor replacement with PCC or FP ordered in the operating room for: 1. Management of bleeding, or 2. Anticipated bleeding in a patient who has been on-pump for \>2 hours or has undergone a complex procedure (e.g., aortocoronary bypass \[ACB\] plus aortic valve replacement) 3. Coagulation factor deficiency, either known to exist (e.g., as indicated by elevated EXTEM clotting time \[CT\] or INR) or suspected based on the clinical situation 4. Patients who have given written informed consent. In United States patients will provide informed consent prior to surgery. In Canada, informed consent will be obtained after surgery, in accordance with Article 3.7A of the 2018 Tri- Council Policy Statement on the Ethical Conduct for Research Involving Humans.
Exclusion criteria
1. Undergoing heart transplantation, insertion or removal of ventricular assist devices (not including intra-aortic balloon pump \[IABP\]) or repair of thoracoabdominal aneurysm 2. Critical state immediately before surgery with high probability of death within 24 hours of surgery (e.g., acute aortic dissection, cardiac arrest within 24 hours before surgery) 3. Severe right heart failure (clinical diagnosis ± echocardiography) 4. Known contraindications to heparin 5. PCC required for reversal of warfarin or direct oral anticoagulant (DOAC; dabigatran, rivaroxaban, apixaban or edoxaban) within 3 days prior to or during surgery 6. Known thromboembolic event (TEE) within 3 months prior to surgery 7. History of severe allergic reactions to PCC or FP 8. Individuals who have immunoglobulin A (IgA) deficiency with known antibodies against IgA 9. Refusal of allogeneic blood products 10. Known pregnancy 11. Currently enrolled in other interventional clinical trials
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Requiring Additional Hemostatic Intervention | 60 minutes to 24 hours after first dose of IMP | Defined as 'effective' if no additional hemostatic intervention, such as administration of any systemic hemostatic agents (including platelets, cryoprecipitate, fibrinogen concentrate, activated recombinant factor VII \[rFVIIa\], other coagulation factor products or a second dose of IMP) or any hemostatic interventions (including surgical re-opening for bleeding) is required from 60 minutes to 24 hours after initiation of the first dose of IMP. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare the Amount of Chest Tube Drainage Between the Octaplex and FP Groups. | 12 and 24 hours after chest closure | — |
| Compare the Incidence of Severe to Massive Bleeding Between the Octaplex and FP Groups Using a Modification of the Universal Definition of Perioperative Bleeding (UDPB). | 24 hours after surgery start, after the end of CPB and after IMP initiation | Yes or no refers to whether severe to massive bleeding was present. |
| Compare Efficacy in Terms of the Mean Number of Total Allogeneic Blood Products (ABPs) (IMP and Non-IMP) Transfused Between the Octaplex and FP Groups. | First 24 hours after the end of CPB | — |
| Compare Efficacy in Terms of the Mean Number of Total Non-IMP Allogeneic Blood Products Transfused Between the Octaplex and FP Groups. | First 24 hours after the end of CPB | — |
| Compare Efficacy in Terms of the Mean Number of Total Non-IMP Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | First 24 hours and 7 days after IMP initiation | — |
| Compare Incidence of Surgical Re-exploration Between Octaplex and FP Groups | 24 hours after start of surgery, after the end of CPB and after IMP initiation | — |
| Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | 24 hours and 7 days after start of surgery, and after the end of CPB and after IMP initiation | — |
| Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | 24 hours and 7 days after start of surgery and after the end of CPB and after IMP initiation | — |
| Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | 24 hours and 7 days after the start of surgery, after the end of CPB and after IMP initiation | — |
| Compare Incidence of Intracerebral Hemorrhage Between the Octaplex and FP Groups | 24 hours after start of surgery, after the end of CPB and after IMP initiation | — |
| Compare Incidence of Gastrointestinal Hemorrhage Between Octaplex and FP Groups | 24 hours after start of surgery, after the end of CPB and after IMP initiation | — |
| Comparison of the Effect of Octaplex Versus FP Administration on the Change in International Normalised Ratio (INR) Before and After Therapy Administration. | Within 30 minutes before to 60 minutes after the initiation of IMP administration. | The international normalized ratio (INR) is a standardized measure of prothrombin time (PT), ensuring consistency in results across different laboratories. The normal range for INR is around 0.8 to 1.2. Higher INR values indicate a slower clotting time and are associated with bleeding. Effective procoagulant therapy can reduce/normalize the INR. INR reduction was considered successful if the magnitude of the reduction was \>1.0 or the post-treatment level dropped below 1.5 (INR \>1.5 indicates that one or more coagulation factor levels are below the 30% critical threshold) |
| Comparison of the Effect of Octaplex Versus FP Administration on the Change in Prothrombin Time (PT) | Within 75 minutes before to within 75 minutes after the initiation of IMP administration | The prothrombin time (PT) measures the time it takes for clotting to occur, primarily assessing the extrinsic pathway of the coagulation cascade. Normal PT values range from 9 to 13 seconds. Higher PT values indicate a prolonged clotting time, suggesting potential issues with clotting factors such as fibrinogen, factors V, VII, and X and prothrombin, and are associated with bleeding. Effective procoagulant therapy can reduce/normalize the PT. |
| Comparison of Global Hemostatic Response Based on Requirement of Additional Hemostatic Intervention and Decreased Hemoglobin Levels | 60 minutes to 24 hours after first dose of IMP | Defined as 'positive' if no additional hemostatic intervention is required and hemoglobin levels decrease by \<30% (after accounting for red cell transfusions) from 60 minutes to 24 hours after initiation of the first dose of IMP. |
| Comparison of the Effect of Octaplex Versus FP Administration on the Change in Activated Partial Thromboplastin Time (aPTT) | Within 75 minutes before to within 75 minutes after the initiation of IMP administration | Activated partial thromboplastin time (aPTT) is a standard laboratory test that measures how long it takes (in seconds) for clotting to occur (in the presence of an activator). It evaluates the intrinsic and common pathways of the coagulation cascade, assessing factors such as VIII, IX, XI, and XII, as well as fibrinogen. Prolonged aPTT may signify deficiencies in these clotting factors and is associated with bleeding. Effective procoagulant therapy can shorten/normalize the aPTT. |
| Comparison of the Effect of Octaplex Versus FP Administration on the Change in ROTEM EXTEM CT | Within 75 minutes before to within 75 minutes after the initiation of IMP administration | A rotational thromboelastometry (ROTEM; Werfen) device can be used at the bedside to rapidly assess the patient's coagulation status. Different viscoelastic tests can be performed to assess the dynamics of clot formation and lysis. Specifically, the EXTEM test is activated with tissue factor and evaluates the extrinsic coagulation pathway, with clotting time (CT) providing a measure (in seconds) of how quickly a clot starts forming. Prolonged EXTEM CT is associated with bleeding. Effective procoagulant therapy can reduce/normalize the EXTEM CT. |
| Comparison of the Effect of Octaplex Versus FP Administration on the Change in ROTEM EXTEM MCF | Within 75 minutes before to within 75 minutes after the initiation of IMP administration | A rotational thromboelastometry (ROTEM; Werfen) device can be used at the bedside to rapidly assess the patient's coagulation status. Different viscoelastic tests can be performed to assess the dynamics of clot formation and lysis. Specifically, the EXTEM test is activated with tissue factor and evaluates the extrinsic coagulation pathway, with maximum clot firmness (MCF) providing a measure (in mm) of the strength of the clot. Reduced EXTEM MCF is associated with bleeding. Effective procoagulant therapy can increase/normalize the EXTEM MCF. |
| Comparison of the Effect of Octaplex Versus FP Administration on the Change in ROTEM FIBTEM MCF | Within 75 minutes before to within 75 minutes after the initiation of IMP administration | A rotational thromboelastometry (ROTEM; Werfen) device can be used at the bedside to rapidly assess the patient's coagulation status. Different viscoelastic tests can be performed to assess the dynamics of clot formation and lysis. Specifically, the FIBTEM test evaluates fibrin-based clotting - it is extrinsically activated with tissue factor and additionally incorporates an inhibitor to eliminate the contribution of platelets to clotting. Maximum clot firmness (MCF) in the FIBTEM test provides a measure (in mm) of the strength of the fibrin-based clot. Reduced FIBTEM MCF is associated with bleeding. Effective procoagulant therapy to restore fibrinogen can increase/normalize the FIBTEM MCF. |
| Comparison of the Effect of Octaplex Versus FP Administration on the Change in Platelet Count Measured by Plateletworks | Within 75 minutes before to within 75 minutes after the initiation of IMP administration | — |
| Comparison of the Effect of Octaplex Versus FP Administration on the Change in Platelet Function Measured by Plateletworks | Within 75 minutes before to within 75 minutes after the initiation of IMP administration | The Plateletworks device (Helena Laboratories) enables rapid bedside screening of platelet function. The system uses an impedance cell counter and Plateletworks reagent tubes to evaluate platelet function and monitor treatment effects. By comparing a baseline total platelet count against the platelet count measured in the presence of an agonist used to stimulate platelet aggregation (ADP, collagen, or arachidonic acid), the tests determine the percent aggregation or inhibition of functional platelets. Manufacturer reference ranges, determined by testing blood samples from healthy volunteers, are 86-100% for ADP, 70-100% for collagen, and 60-100% for arachidonic acid. Values within these ranges indicate 'normal (positive)' platelet aggregation, which is important for clotting; lower values may be considered 'abnormal (negative)' and reflective of platelet inhibition. The manufacturer advises each laboratory to establish their own reference ranges for their patient population. |
| Comparison of Total Time Elapsed From Initiation of the First Dose of IMP to Arrival Into the ICU Between the Octaplex and FP Groups. | From initiation of IMP to arrival at ICU room (within 24 hours) | — |
| Comparison of Incidence of Serious Treatment-emergent Adverse Events Between Octaplex and FP Groups | From the beginning of surgery up to postoperative day 30 | — |
| Comparison of the Duration of Mechanical Ventilation Between Octaplex and FP Groups | From the beginning of surgery up to postoperative day 30 | — |
| Comparison of the Duration of ICU Stay Between Octaplex and FP Groups | From the beginning of surgery up to postoperative day 30 | — |
| Comparison of the Duration of Hospitalization Between Octaplex and FP Groups | From the beginning of surgery up to postoperative day 30 | — |
| Comparison of the Incidence of Death Between Octaplex and FP Groups | Up to 30 days after the end of CPB | — |
| Comparison of the Number of Days Alive and Out of Hospital Between Octaplex and FP Groups | From the beginning of surgery up to postoperative day 30 | — |
| Comparison of the Effect of Octaplex Versus FP Administration on the Change in Fibrinogen Activity | Within 75 minutes before to within 75 minutes after the initiation of IMP administration | — |
Countries
Canada, United States
Participant flow
Recruitment details
Participants were recruited based on physician referral at 10 Canadian sites and 2 US sites. The first participant was enrolled in November 2022 and the last patient completed the study in June 2024.
Pre-assignment details
Of 538 enrolled participants, 420 met the inclusion criteria and were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Octaplex Participants were administered Octaplex according to a recommended initial dose of 1,500 IU for patients weighing ≤60 kg and 2,000 IU for patients weighing \>60 kg. A second dose of IMP could be administered if the patient continued to have at least moderate bleeding and suspected coagulation deficiency (e.g., INR ≥1.5) after completion of the first dose, up to the maximum allowable dose (3,000 IU if ≤60 kg or 4,000 IU if \>60 kg).
Octaplex: Prothrombin complex concentrate | 213 |
| Frozen Plasma Participants were administered FP according to a recommended initial dose of 3 U for patients weighing ≤60 kg and 4 U for patients weighing \>60 kg. A second dose of IMP could be administered if the patient continued to have at least moderate bleeding and suspected coagulation deficiency (e.g., INR ≥1.5) after completion of the first dose, up to the maximum allowable dose (6 U if ≤60 kg or 8 U if \>60 kg).
Frozen Plasma Product, Human | 207 |
| Total | 420 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 7 | 8 |
| Overall Study | Lost to Follow-up | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Frozen Plasma | Octaplex |
|---|---|---|---|
| Age, Continuous | 62.84 years STANDARD_DEVIATION 13.829 | 61.68 years STANDARD_DEVIATION 14.002 | 63.97 years STANDARD_DEVIATION 13.596 |
| Body Height | 171.42 centimeter (cm) STANDARD_DEVIATION 10.318 | 171.83 centimeter (cm) STANDARD_DEVIATION 10.565 | 171.03 centimeter (cm) STANDARD_DEVIATION 10.082 |
| Body Mass Index (BMI) | 28.55 kilogram per square meter (kg/m²) STANDARD_DEVIATION 5.71 | 28.20 kilogram per square meter (kg/m²) STANDARD_DEVIATION 5.403 | 28.88 kilogram per square meter (kg/m²) STANDARD_DEVIATION 5.986 |
| Body Weight | 84.13 kilogram (kg) STANDARD_DEVIATION 19.414 | 83.62 kilogram (kg) STANDARD_DEVIATION 19.52 | 84.63 kilogram (kg) STANDARD_DEVIATION 19.344 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 264 Participants | 132 Participants | 132 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 152 Participants | 73 Participants | 79 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 41 Participants | 21 Participants | 20 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 94 Participants | 45 Participants | 49 Participants |
| Race (NIH/OMB) White | 275 Participants | 137 Participants | 138 Participants |
| Sex: Female, Male Female | 111 Participants | 55 Participants | 56 Participants |
| Sex: Female, Male Male | 309 Participants | 152 Participants | 157 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 213 | 8 / 207 |
| other Total, other adverse events | 206 / 213 | 201 / 207 |
| serious Total, serious adverse events | 77 / 213 | 98 / 207 |
Outcome results
Primary
Number of Patients Requiring Additional Hemostatic Intervention
Defined as 'effective' if no additional hemostatic intervention, such as administration of any systemic hemostatic agents (including platelets, cryoprecipitate, fibrinogen concentrate, activated recombinant factor VII \[rFVIIa\], other coagulation factor products or a second dose of IMP) or any hemostatic interventions (including surgical re-opening for bleeding) is required from 60 minutes to 24 hours after initiation of the first dose of IMP.
Time frame: 60 minutes to 24 hours after first dose of IMP
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Octaplex | Number of Patients Requiring Additional Hemostatic Intervention | Effective | 166 Participants |
| Octaplex | Number of Patients Requiring Additional Hemostatic Intervention | Ineffective | 47 Participants |
| Frozen Plasma | Number of Patients Requiring Additional Hemostatic Intervention | Effective | 125 Participants |
| Frozen Plasma | Number of Patients Requiring Additional Hemostatic Intervention | Ineffective | 82 Participants |
p-value: <0.000195% CI: [8.7, 26.4]Two-sided Farrington-Manning score test.
Secondary
Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups.
Time frame: 24 hours and 7 days after start of surgery and after the end of CPB and after IMP initiation
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | FP excluding IMP (Within 24 hours after IMP start) | No | 205 Participants |
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | FP excluding IMP (Within 24 hours after IMP start) | Yes | 8 Participants |
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | RBCs (Within 24 hours after IMP start) | No | 116 Participants |
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | RBCs (Within 24 hours after IMP start) | Yes | 97 Participants |
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Platelets (Within 24 hours after IMP start) | No | 116 Participants |
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Platelets (Within 24 hours after IMP start) | Yes | 97 Participants |
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Cryoprecipitate (Within 24 hours after IMP start) | No | 204 Participants |
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Cryoprecipitate (Within 24 hours after IMP start) | Yes | 9 Participants |
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Any individual ABP (Within 24 hours after IMP start) | No | 82 Participants |
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Any individual ABP (Within 24 hours after IMP start) | Yes | 131 Participants |
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | FP excluding IMP (Within 7 days after IMP start) | No | 205 Participants |
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | FP excluding IMP (Within 7 days after IMP start) | Yes | 8 Participants |
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | RBCs (Within 7 days after IMP start) | No | 82 Participants |
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | RBCs (Within 7 days after IMP start) | Yes | 131 Participants |
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Platelets (Within 7 days after IMP start) | No | 112 Participants |
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Platelets (Within 7 days after IMP start) | Yes | 101 Participants |
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Cryoprecipitate (Within 7 days after IMP start) | No | 204 Participants |
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Cryoprecipitate (Within 7 days after IMP start) | Yes | 9 Participants |
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Any individual ABP (Within 7 days after IMP start) | No | 58 Participants |
| Octaplex | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Any individual ABP (Within 7 days after IMP start) | Yes | 155 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Cryoprecipitate (Within 7 days after IMP start) | Yes | 12 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | FP excluding IMP (Within 24 hours after IMP start) | No | 200 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | FP excluding IMP (Within 7 days after IMP start) | No | 195 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | FP excluding IMP (Within 24 hours after IMP start) | Yes | 7 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Platelets (Within 7 days after IMP start) | Yes | 110 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | RBCs (Within 24 hours after IMP start) | No | 75 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | FP excluding IMP (Within 7 days after IMP start) | Yes | 12 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | RBCs (Within 24 hours after IMP start) | Yes | 132 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Any individual ABP (Within 7 days after IMP start) | Yes | 167 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Platelets (Within 24 hours after IMP start) | No | 99 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | RBCs (Within 7 days after IMP start) | No | 53 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Platelets (Within 24 hours after IMP start) | Yes | 108 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Cryoprecipitate (Within 7 days after IMP start) | No | 195 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Cryoprecipitate (Within 24 hours after IMP start) | No | 195 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | RBCs (Within 7 days after IMP start) | Yes | 154 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Cryoprecipitate (Within 24 hours after IMP start) | Yes | 12 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Any individual ABP (Within 7 days after IMP start) | No | 40 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Any individual ABP (Within 24 hours after IMP start) | No | 56 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Platelets (Within 7 days after IMP start) | No | 97 Participants |
| Frozen Plasma | Compare Efficacy in Terms of the Incidence of Transfusion of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Any individual ABP (Within 24 hours after IMP start) | Yes | 151 Participants |
Comparison: FP excluding IMP (Within 24 hours after IMP start)p-value: 0.836495% CI: [0.32, 2.52]Regression, Logistic
Comparison: RBCs (Within 24 hours after IMP start)p-value: 0.000295% CI: [1.42, 3.11]Regression, Logistic
Comparison: Platelets (Within 24 hours after IMP start)p-value: 0.174295% CI: [0.89, 1.91]Regression, Logistic
Comparison: Cryoprecipitate (Within 24 hours after IMP start)p-value: 0.461895% CI: [0.58, 3.38]Regression, Logistic
Comparison: Any individual ABP (Within 24 hours after IMP start)p-value: 0.012995% CI: [1.12, 2.55]Regression, Logistic
Comparison: FP excluding IMP (Within 7 days after IMP start)p-value: 0.329795% CI: [0.63, 3.94]Regression, Logistic
Comparison: RBCs (Within 7 days after IMP start)p-value: 0.004995% CI: [1.2, 2.76]Regression, Logistic
Comparison: Platelets (Within 7 days after IMP start)p-value: 0.241795% CI: [0.86, 1.84]Regression, Logistic
Comparison: Cryoprecipitate (Within 7 days after IMP start)p-value: 0.461895% CI: [0.58, 3.38]Regression, Logistic
Comparison: Any individual ABP (Within 7 days after IMP start)p-value: 0.056495% CI: [0.99, 2.47]Regression, Logistic
Secondary
Compare Efficacy in Terms of the Mean Number of Total Allogeneic Blood Products (ABPs) (IMP and Non-IMP) Transfused Between the Octaplex and FP Groups.
Time frame: First 24 hours after the end of CPB
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octaplex | Compare Efficacy in Terms of the Mean Number of Total Allogeneic Blood Products (ABPs) (IMP and Non-IMP) Transfused Between the Octaplex and FP Groups. | 6.61 total ABPs | Standard Deviation 6.95 |
| Frozen Plasma | Compare Efficacy in Terms of the Mean Number of Total Allogeneic Blood Products (ABPs) (IMP and Non-IMP) Transfused Between the Octaplex and FP Groups. | 13.79 total ABPs | Standard Deviation 11.42 |
p-value: <0.000195% CI: [0.41, 0.57]Counting regression
Secondary
Compare Efficacy in Terms of the Mean Number of Total Non-IMP Allogeneic Blood Components Transfused Between the Octaplex and FP Groups.
Time frame: First 24 hours and 7 days after IMP initiation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Octaplex | Compare Efficacy in Terms of the Mean Number of Total Non-IMP Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | During the first 24 hours after IMP start | 4.14 Total non-IMP ABPs | Standard Deviation 6.25 |
| Octaplex | Compare Efficacy in Terms of the Mean Number of Total Non-IMP Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | During the first 7 days after IMP start | 5.20 Total non-IMP ABPs | Standard Deviation 8.43 |
| Frozen Plasma | Compare Efficacy in Terms of the Mean Number of Total Non-IMP Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | During the first 24 hours after IMP start | 6.73 Total non-IMP ABPs | Standard Deviation 10.14 |
| Frozen Plasma | Compare Efficacy in Terms of the Mean Number of Total Non-IMP Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | During the first 7 days after IMP start | 8.87 Total non-IMP ABPs | Standard Deviation 16.04 |
Comparison: During the first 24 hours after IMP startp-value: 0.00195% CI: [0.46, 0.82]Counting regression
Comparison: During the first 7 days after IMP startp-value: <0.000195% CI: [0.45, 0.76]Counting regression
Secondary
Compare Efficacy in Terms of the Mean Number of Total Non-IMP Allogeneic Blood Products Transfused Between the Octaplex and FP Groups.
Time frame: First 24 hours after the end of CPB
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octaplex | Compare Efficacy in Terms of the Mean Number of Total Non-IMP Allogeneic Blood Products Transfused Between the Octaplex and FP Groups. | 6.61 total non-IMP ABPs | Standard Deviation 6.95 |
| Frozen Plasma | Compare Efficacy in Terms of the Mean Number of Total Non-IMP Allogeneic Blood Products Transfused Between the Octaplex and FP Groups. | 9.33 total non-IMP ABPs | Standard Deviation 10.64 |
p-value: 0.001595% CI: [0.57, 0.88]Counting regression
Secondary
Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups
Time frame: 24 hours and 7 days after the start of surgery, after the end of CPB and after IMP initiation
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Octaplex | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | PCC excluding IMP (Within 24 hours after IMP start) | No | 212 Participants |
| Octaplex | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | Fibrinogen concentrate (Within 24 hours after IMP start) | No | 167 Participants |
| Octaplex | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | Fibrinogen concentrate (Within 24 hours after IMP start) | Yes | 46 Participants |
| Octaplex | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | rFVIIa (Within 24 hours after IMP start) | No | 211 Participants |
| Octaplex | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | rFVIIa (Within 24 hours after IMP start) | Yes | 2 Participants |
| Octaplex | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | PCC excluding IMP (Within 24 hours after IMP start) | Yes | 1 Participants |
| Octaplex | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | Any coagulation factor product (Within 24 hours after IMP start) | No | 164 Participants |
| Octaplex | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | Any coagulation factor product (Within 24 hours after IMP start) | Yes | 49 Participants |
| Octaplex | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | Fibrinogen concentrate (Within 7 days after IMP start) | No | 167 Participants |
| Octaplex | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | Fibrinogen concentrate (Within 7 days after IMP start) | Yes | 46 Participants |
| Octaplex | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | rFVIIa (Within 7 days after IMP start) | No | 211 Participants |
| Octaplex | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | rFVIIa (Within 7 days after IMP start) | Yes | 2 Participants |
| Octaplex | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | PCC excluding IMP (Within 7 days after IMP start) | No | 212 Participants |
| Octaplex | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | PCC excluding IMP (Within 7 days after IMP start) | Yes | 1 Participants |
| Octaplex | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | Any coagulation factor product (Within 7 days after IMP start) | No | 164 Participants |
| Octaplex | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | Any coagulation factor product (Within 7 days after IMP start) | Yes | 49 Participants |
| Frozen Plasma | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | Any coagulation factor product (Within 7 days after IMP start) | Yes | 62 Participants |
| Frozen Plasma | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | Fibrinogen concentrate (Within 7 days after IMP start) | No | 156 Participants |
| Frozen Plasma | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | Fibrinogen concentrate (Within 24 hours after IMP start) | No | 159 Participants |
| Frozen Plasma | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | PCC excluding IMP (Within 7 days after IMP start) | No | 190 Participants |
| Frozen Plasma | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | Fibrinogen concentrate (Within 24 hours after IMP start) | Yes | 48 Participants |
| Frozen Plasma | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | Fibrinogen concentrate (Within 7 days after IMP start) | Yes | 51 Participants |
| Frozen Plasma | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | rFVIIa (Within 24 hours after IMP start) | No | 197 Participants |
| Frozen Plasma | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | Any coagulation factor product (Within 7 days after IMP start) | No | 145 Participants |
| Frozen Plasma | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | rFVIIa (Within 24 hours after IMP start) | Yes | 10 Participants |
| Frozen Plasma | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | PCC excluding IMP (Within 24 hours after IMP start) | No | 190 Participants |
| Frozen Plasma | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | rFVIIa (Within 7 days after IMP start) | No | 197 Participants |
| Frozen Plasma | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | PCC excluding IMP (Within 24 hours after IMP start) | Yes | 17 Participants |
| Frozen Plasma | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | PCC excluding IMP (Within 7 days after IMP start) | Yes | 17 Participants |
| Frozen Plasma | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | Any coagulation factor product (Within 24 hours after IMP start) | No | 148 Participants |
| Frozen Plasma | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | rFVIIa (Within 7 days after IMP start) | Yes | 10 Participants |
| Frozen Plasma | Compare Incidence of Administration of Non-IMP Coagulation Factor Products Between Octaplex and FP Groups | Any coagulation factor product (Within 24 hours after IMP start) | Yes | 59 Participants |
Comparison: Fibrinogen concentrate (Within 24 hours after IMP start)p-value: 0.695695% CI: [0.69, 1.73]Regression, Logistic
p-value: 0.031795% CI: [1.12, 50.7]Regression, Logistic
Comparison: PCC excluding IMP (Within 24 hours after IMP start)p-value: <0.000195% CI: [2.9, 796.37]Regression, Logistic
Comparison: Any coagulation factor product (Within 24 hours after IMP start)p-value: 0.198195% CI: [0.86, 2.07]Regression, Logistic
Comparison: Fibrinogen concentrate (Within 7 days after IMP start)p-value: 0.459995% CI: [0.75, 1.87]Regression, Logistic
Comparison: rFVIIa (Within 7 days after IMP start)p-value: 0.031795% CI: [1.12, 50.7]Regression, Logistic
Comparison: PCC excluding IMP (Within 7 days after IMP start)p-value: <0.000195% CI: [2.9, 796.37]Regression, Logistic
Comparison: Any coagulation factor product (Within 7 days after IMP start)p-value: 0.107395% CI: [0.93, 2.21]Regression, Logistic
Secondary
Compare Incidence of Gastrointestinal Hemorrhage Between Octaplex and FP Groups
Time frame: 24 hours after start of surgery, after the end of CPB and after IMP initiation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Octaplex | Compare Incidence of Gastrointestinal Hemorrhage Between Octaplex and FP Groups | 24 hours after start of surgery | 0 participants |
| Octaplex | Compare Incidence of Gastrointestinal Hemorrhage Between Octaplex and FP Groups | After the end of CPB | 0 participants |
| Octaplex | Compare Incidence of Gastrointestinal Hemorrhage Between Octaplex and FP Groups | After IMP initiation | 0 participants |
| Frozen Plasma | Compare Incidence of Gastrointestinal Hemorrhage Between Octaplex and FP Groups | 24 hours after start of surgery | 0 participants |
| Frozen Plasma | Compare Incidence of Gastrointestinal Hemorrhage Between Octaplex and FP Groups | After the end of CPB | 0 participants |
| Frozen Plasma | Compare Incidence of Gastrointestinal Hemorrhage Between Octaplex and FP Groups | After IMP initiation | 0 participants |
Secondary
Compare Incidence of Intracerebral Hemorrhage Between the Octaplex and FP Groups
Time frame: 24 hours after start of surgery, after the end of CPB and after IMP initiation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Octaplex | Compare Incidence of Intracerebral Hemorrhage Between the Octaplex and FP Groups | 24 hours after start of surgery | 0 participants |
| Octaplex | Compare Incidence of Intracerebral Hemorrhage Between the Octaplex and FP Groups | After the end of CPB | 0 participants |
| Octaplex | Compare Incidence of Intracerebral Hemorrhage Between the Octaplex and FP Groups | After IMP initiation | 0 participants |
| Frozen Plasma | Compare Incidence of Intracerebral Hemorrhage Between the Octaplex and FP Groups | After the end of CPB | 0 participants |
| Frozen Plasma | Compare Incidence of Intracerebral Hemorrhage Between the Octaplex and FP Groups | 24 hours after start of surgery | 0 participants |
| Frozen Plasma | Compare Incidence of Intracerebral Hemorrhage Between the Octaplex and FP Groups | After IMP initiation | 0 participants |
Secondary
Compare Incidence of Surgical Re-exploration Between Octaplex and FP Groups
Time frame: 24 hours after start of surgery, after the end of CPB and after IMP initiation
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Octaplex | Compare Incidence of Surgical Re-exploration Between Octaplex and FP Groups | Within 24 hours after surgery start | No | 200 Participants |
| Octaplex | Compare Incidence of Surgical Re-exploration Between Octaplex and FP Groups | Within 24 hours after surgery start | Yes | 13 Participants |
| Octaplex | Compare Incidence of Surgical Re-exploration Between Octaplex and FP Groups | Within 24 hours after CPB end | No | 199 Participants |
| Octaplex | Compare Incidence of Surgical Re-exploration Between Octaplex and FP Groups | Within 24 hours after CPB end | Yes | 14 Participants |
| Octaplex | Compare Incidence of Surgical Re-exploration Between Octaplex and FP Groups | Within 24 hours after IMP start | No | 199 Participants |
| Octaplex | Compare Incidence of Surgical Re-exploration Between Octaplex and FP Groups | Within 24 hours after IMP start | Yes | 14 Participants |
| Frozen Plasma | Compare Incidence of Surgical Re-exploration Between Octaplex and FP Groups | Within 24 hours after IMP start | No | 187 Participants |
| Frozen Plasma | Compare Incidence of Surgical Re-exploration Between Octaplex and FP Groups | Within 24 hours after surgery start | No | 189 Participants |
| Frozen Plasma | Compare Incidence of Surgical Re-exploration Between Octaplex and FP Groups | Within 24 hours after CPB end | Yes | 20 Participants |
| Frozen Plasma | Compare Incidence of Surgical Re-exploration Between Octaplex and FP Groups | Within 24 hours after surgery start | Yes | 18 Participants |
| Frozen Plasma | Compare Incidence of Surgical Re-exploration Between Octaplex and FP Groups | Within 24 hours after IMP start | Yes | 20 Participants |
| Frozen Plasma | Compare Incidence of Surgical Re-exploration Between Octaplex and FP Groups | Within 24 hours after CPB end | No | 187 Participants |
Comparison: Within 24 hours after CPB endp-value: 0.378295% CI: [0.6429, 3.2013]Regression, Logistic
Comparison: Within 24 hours after IMP startp-value: 0.378295% CI: [0.6429, 3.2013]Regression, Logistic
Comparison: Within 24 hours after surgery startp-value: 0.489995% CI: [0.5902, 3.0062]Regression, Logistic
Secondary
Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups.
Time frame: 24 hours and 7 days after start of surgery, and after the end of CPB and after IMP initiation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Octaplex | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | FP including IMP (During the first 24 hours after IMP start) | 0.19 ABPs | Standard Deviation 1.12 |
| Octaplex | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | FP excluding IMP (During the first 24 hours after IMP start) | 0.19 ABPs | Standard Deviation 1.12 |
| Octaplex | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | RBCs (During the first 24 hours after IMP start) | 1.05 ABPs | Standard Deviation 1.72 |
| Octaplex | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Platelets (During the first 24 hours after IMP start) | 2.89 ABPs | Standard Deviation 4.5 |
| Octaplex | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Cryoprecipitate (During the first 24 hours after IMP start) | 0.08 ABPs | Standard Deviation 0.42 |
| Octaplex | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | FP including IMP (During the first 7 days after IMP start) | 0.23 ABPs | Standard Deviation 1.273 |
| Octaplex | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | FP excluding IMP (During the first 7 days after IMP start) | 0.23 ABPs | Standard Deviation 1.273 |
| Octaplex | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Red blood cells (During the first 7 days after IMP start) | 1.7 ABPs | Standard Deviation 2.378 |
| Octaplex | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Platelets (During the first 7 days after IMP start) | 3.27 ABPs | Standard Deviation 5.827 |
| Octaplex | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Cryoprecipitate (During the first 7 days after IMP start) | 0.08 ABPs | Standard Deviation 0.421 |
| Frozen Plasma | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Red blood cells (During the first 7 days after IMP start) | 2.9 ABPs | Standard Deviation 3.466 |
| Frozen Plasma | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | FP including IMP (During the first 24 hours after IMP start) | 4.70 ABPs | Standard Deviation 2.47 |
| Frozen Plasma | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | FP including IMP (During the first 7 days after IMP start) | 7.25 ABPs | Standard Deviation 34.818 |
| Frozen Plasma | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | FP excluding IMP (During the first 24 hours after IMP start) | 0.23 ABPs | Standard Deviation 1.63 |
| Frozen Plasma | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Cryoprecipitate (During the first 7 days after IMP start) | 0.16 ABPs | Standard Deviation 0.765 |
| Frozen Plasma | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | RBCs (During the first 24 hours after IMP start) | 2.02 ABPs | Standard Deviation 2.58 |
| Frozen Plasma | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | FP excluding IMP (During the first 7 days after IMP start) | 2.78 ABPs | Standard Deviation 34.792 |
| Frozen Plasma | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Platelets (During the first 24 hours after IMP start) | 4.48 ABPs | Standard Deviation 6.8 |
| Frozen Plasma | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Platelets (During the first 7 days after IMP start) | 5.6 ABPs | Standard Deviation 11.53 |
| Frozen Plasma | Compare Mean Number of Individual Allogeneic Blood Components Transfused Between the Octaplex and FP Groups. | Cryoprecipitate (During the first 24 hours after IMP start) | 0.14 ABPs | Standard Deviation 0.61 |
Comparison: FP including IMP (During the first 24 hours after IMP start)p-value: <0.000195% CI: [0.03, 0.06]Negative binomial regression
Comparison: FP excluding IMP (During the first 24 hours after IMP start)p-value: 0.852295% CI: [0.15, 4.82]Negative binomial regression
Comparison: RBCs (During the first 24 hours after IMP start)p-value: <0.000195% CI: [0.4, 0.68]Negative binomial regression
Comparison: Platelets (During the first 24 hours after IMP start)p-value: 0.016995% CI: [0.45, 0.92]Negative binomial regression
Comparison: Cryoprecipitate (During the first 24 hours after IMP start)p-value: 0.328895% CI: [0.18, 1.76]Negative binomial regression
Comparison: FP including IMP (During the first 7 days after IMP start)p-value: <0.000195% CI: [0.04, 0.06]Negative binomial regression
Comparison: FP excluding IMP (During the first 7 days after IMP start)p-value: 0.543995% CI: [0.14, 2.84]Negative binomial regression
Comparison: Red blood cells (During the first 7 days after IMP start)p-value: <0.000195% CI: [0.47, 0.74]Negative binomial regression
Comparison: Platelets (During the first 7 days after IMP start)p-value: 0.004295% CI: [0.4, 0.84]Negative binomial regression
Comparison: Cryoprecipitate (During the first 7 days after IMP start)p-value: 0.224195% CI: [0.15, 1.56]Negative binomial regression
Secondary
Compare the Amount of Chest Tube Drainage Between the Octaplex and FP Groups.
Time frame: 12 and 24 hours after chest closure
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Octaplex | Compare the Amount of Chest Tube Drainage Between the Octaplex and FP Groups. | 12 hours after chest closure | 471.20 Milliliters (mL) | Standard Deviation 358.32 |
| Octaplex | Compare the Amount of Chest Tube Drainage Between the Octaplex and FP Groups. | 24 hours after chest closure | 690.90 Milliliters (mL) | Standard Deviation 465.62 |
| Frozen Plasma | Compare the Amount of Chest Tube Drainage Between the Octaplex and FP Groups. | 12 hours after chest closure | 641.90 Milliliters (mL) | Standard Deviation 465.17 |
| Frozen Plasma | Compare the Amount of Chest Tube Drainage Between the Octaplex and FP Groups. | 24 hours after chest closure | 922.90 Milliliters (mL) | Standard Deviation 631.9 |
Comparison: 12 hours after chest closurep-value: <0.000195% CI: [-250.24, -91.22]ANOVA
Comparison: 24 hours after chest closurep-value: <0.000195% CI: [-338.17, -125.67]ANOVA
Secondary
Compare the Incidence of Severe to Massive Bleeding Between the Octaplex and FP Groups Using a Modification of the Universal Definition of Perioperative Bleeding (UDPB).
Yes or no refers to whether severe to massive bleeding was present.
Time frame: 24 hours after surgery start, after the end of CPB and after IMP initiation
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Octaplex | Compare the Incidence of Severe to Massive Bleeding Between the Octaplex and FP Groups Using a Modification of the Universal Definition of Perioperative Bleeding (UDPB). | Within 24 hours after IMP start | No | 183 Participants |
| Octaplex | Compare the Incidence of Severe to Massive Bleeding Between the Octaplex and FP Groups Using a Modification of the Universal Definition of Perioperative Bleeding (UDPB). | Within 24 hours after IMP start | Yes | 30 Participants |
| Octaplex | Compare the Incidence of Severe to Massive Bleeding Between the Octaplex and FP Groups Using a Modification of the Universal Definition of Perioperative Bleeding (UDPB). | Within 24 hours after surgery start | No | 176 Participants |
| Octaplex | Compare the Incidence of Severe to Massive Bleeding Between the Octaplex and FP Groups Using a Modification of the Universal Definition of Perioperative Bleeding (UDPB). | Within 24 hours after surgery start | Yes | 37 Participants |
| Octaplex | Compare the Incidence of Severe to Massive Bleeding Between the Octaplex and FP Groups Using a Modification of the Universal Definition of Perioperative Bleeding (UDPB). | Within 24 hours after CBP end | No | 183 Participants |
| Octaplex | Compare the Incidence of Severe to Massive Bleeding Between the Octaplex and FP Groups Using a Modification of the Universal Definition of Perioperative Bleeding (UDPB). | Within 24 hours after CBP end | Yes | 30 Participants |
| Frozen Plasma | Compare the Incidence of Severe to Massive Bleeding Between the Octaplex and FP Groups Using a Modification of the Universal Definition of Perioperative Bleeding (UDPB). | Within 24 hours after CBP end | No | 136 Participants |
| Frozen Plasma | Compare the Incidence of Severe to Massive Bleeding Between the Octaplex and FP Groups Using a Modification of the Universal Definition of Perioperative Bleeding (UDPB). | Within 24 hours after IMP start | No | 136 Participants |
| Frozen Plasma | Compare the Incidence of Severe to Massive Bleeding Between the Octaplex and FP Groups Using a Modification of the Universal Definition of Perioperative Bleeding (UDPB). | Within 24 hours after surgery start | Yes | 78 Participants |
| Frozen Plasma | Compare the Incidence of Severe to Massive Bleeding Between the Octaplex and FP Groups Using a Modification of the Universal Definition of Perioperative Bleeding (UDPB). | Within 24 hours after IMP start | Yes | 71 Participants |
| Frozen Plasma | Compare the Incidence of Severe to Massive Bleeding Between the Octaplex and FP Groups Using a Modification of the Universal Definition of Perioperative Bleeding (UDPB). | Within 24 hours after CBP end | Yes | 71 Participants |
| Frozen Plasma | Compare the Incidence of Severe to Massive Bleeding Between the Octaplex and FP Groups Using a Modification of the Universal Definition of Perioperative Bleeding (UDPB). | Within 24 hours after surgery start | No | 129 Participants |
Comparison: Within 24 hours after IMP startp-value: <0.000195% CI: [1.97, 5.15]Regression, Logistic
Comparison: Within 24 hours after surgery startp-value: <0.000195% CI: [1.83, 4.52]Regression, Logistic
Comparison: Within 24 hours after CPB endp-value: <0.000195% CI: [1.97, 5.15]Regression, Logistic
Secondary
Comparison of Global Hemostatic Response Based on Requirement of Additional Hemostatic Intervention and Decreased Hemoglobin Levels
Defined as 'positive' if no additional hemostatic intervention is required and hemoglobin levels decrease by \<30% (after accounting for red cell transfusions) from 60 minutes to 24 hours after initiation of the first dose of IMP.
Time frame: 60 minutes to 24 hours after first dose of IMP
Population: Data were not available for 2 patients in the FP group due to missing hemoglobin values.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Octaplex | Comparison of Global Hemostatic Response Based on Requirement of Additional Hemostatic Intervention and Decreased Hemoglobin Levels | Negative | 56 Participants |
| Octaplex | Comparison of Global Hemostatic Response Based on Requirement of Additional Hemostatic Intervention and Decreased Hemoglobin Levels | Positive | 157 Participants |
| Frozen Plasma | Comparison of Global Hemostatic Response Based on Requirement of Additional Hemostatic Intervention and Decreased Hemoglobin Levels | Negative | 83 Participants |
| Frozen Plasma | Comparison of Global Hemostatic Response Based on Requirement of Additional Hemostatic Intervention and Decreased Hemoglobin Levels | Positive | 122 Participants |
p-value: 0.002295% CI: [1.26, 2.88]Regression, Logistic
Secondary
Comparison of Incidence of Serious Treatment-emergent Adverse Events Between Octaplex and FP Groups
Time frame: From the beginning of surgery up to postoperative day 30
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Octaplex | Comparison of Incidence of Serious Treatment-emergent Adverse Events Between Octaplex and FP Groups | 77 Participants |
| Frozen Plasma | Comparison of Incidence of Serious Treatment-emergent Adverse Events Between Octaplex and FP Groups | 98 Participants |
Secondary
Comparison of the Duration of Hospitalization Between Octaplex and FP Groups
Time frame: From the beginning of surgery up to postoperative day 30
Population: One patient in the FP group was excluded from analysis due to missing data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Octaplex | Comparison of the Duration of Hospitalization Between Octaplex and FP Groups | 8 days |
| Frozen Plasma | Comparison of the Duration of Hospitalization Between Octaplex and FP Groups | 9 days |
Secondary
Comparison of the Duration of ICU Stay Between Octaplex and FP Groups
Time frame: From the beginning of surgery up to postoperative day 30
Population: Three patients in the FP group were excluded from this analysis due to missing dates of ICU stays
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Octaplex | Comparison of the Duration of ICU Stay Between Octaplex and FP Groups | 4 days |
| Frozen Plasma | Comparison of the Duration of ICU Stay Between Octaplex and FP Groups | 4 days |
Secondary
Comparison of the Duration of Mechanical Ventilation Between Octaplex and FP Groups
Time frame: From the beginning of surgery up to postoperative day 30
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Octaplex | Comparison of the Duration of Mechanical Ventilation Between Octaplex and FP Groups | 1.0 days |
| Frozen Plasma | Comparison of the Duration of Mechanical Ventilation Between Octaplex and FP Groups | 1.0 days |
Secondary
Comparison of the Effect of Octaplex Versus FP Administration on the Change in Activated Partial Thromboplastin Time (aPTT)
Activated partial thromboplastin time (aPTT) is a standard laboratory test that measures how long it takes (in seconds) for clotting to occur (in the presence of an activator). It evaluates the intrinsic and common pathways of the coagulation cascade, assessing factors such as VIII, IX, XI, and XII, as well as fibrinogen. Prolonged aPTT may signify deficiencies in these clotting factors and is associated with bleeding. Effective procoagulant therapy can shorten/normalize the aPTT.
Time frame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octaplex | Comparison of the Effect of Octaplex Versus FP Administration on the Change in Activated Partial Thromboplastin Time (aPTT) | -63.5 seconds | Standard Deviation 121.47 |
| Frozen Plasma | Comparison of the Effect of Octaplex Versus FP Administration on the Change in Activated Partial Thromboplastin Time (aPTT) | -45.6 seconds | — |
p-value: 0.903395% CI: [-450.13, 414.28]ANOVA
Secondary
Comparison of the Effect of Octaplex Versus FP Administration on the Change in Fibrinogen Activity
Time frame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octaplex | Comparison of the Effect of Octaplex Versus FP Administration on the Change in Fibrinogen Activity | 0.1 grams per liter (g/L) | Standard Deviation 0.07 |
| Frozen Plasma | Comparison of the Effect of Octaplex Versus FP Administration on the Change in Fibrinogen Activity | 0.5 grams per liter (g/L) | Standard Deviation 0.57 |
p-value: 0.180895% CI: [-1.1, 0.29]ANOVA
Secondary
Comparison of the Effect of Octaplex Versus FP Administration on the Change in International Normalised Ratio (INR) Before and After Therapy Administration.
The international normalized ratio (INR) is a standardized measure of prothrombin time (PT), ensuring consistency in results across different laboratories. The normal range for INR is around 0.8 to 1.2. Higher INR values indicate a slower clotting time and are associated with bleeding. Effective procoagulant therapy can reduce/normalize the INR. INR reduction was considered successful if the magnitude of the reduction was \>1.0 or the post-treatment level dropped below 1.5 (INR \>1.5 indicates that one or more coagulation factor levels are below the 30% critical threshold)
Time frame: Within 30 minutes before to 60 minutes after the initiation of IMP administration.
Population: The analysis of absolute change included all patients who had INR data available at both pre- and post-IMP time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octaplex | Comparison of the Effect of Octaplex Versus FP Administration on the Change in International Normalised Ratio (INR) Before and After Therapy Administration. | -0.9 international normalised ratio (INR) | Standard Deviation 0.76 |
| Frozen Plasma | Comparison of the Effect of Octaplex Versus FP Administration on the Change in International Normalised Ratio (INR) Before and After Therapy Administration. | -0.7 international normalised ratio (INR) | Standard Deviation 0.91 |
p-value: 0.008195% CI: [-0.26, -0.04]ANOVA
Secondary
Comparison of the Effect of Octaplex Versus FP Administration on the Change in Platelet Count Measured by Plateletworks
Time frame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration
Population: The analysis of absolute change included all patients who had coagulation parameter data available at both pre- and post-IMP time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octaplex | Comparison of the Effect of Octaplex Versus FP Administration on the Change in Platelet Count Measured by Plateletworks | -2.3 10^9 platelets/L | Standard Deviation 22.97 |
| Frozen Plasma | Comparison of the Effect of Octaplex Versus FP Administration on the Change in Platelet Count Measured by Plateletworks | 10.9 10^9 platelets/L | Standard Deviation 38.29 |
p-value: 0.266795% CI: [-37.05, 10.67]ANOVA
Secondary
Comparison of the Effect of Octaplex Versus FP Administration on the Change in Platelet Function Measured by Plateletworks
The Plateletworks device (Helena Laboratories) enables rapid bedside screening of platelet function. The system uses an impedance cell counter and Plateletworks reagent tubes to evaluate platelet function and monitor treatment effects. By comparing a baseline total platelet count against the platelet count measured in the presence of an agonist used to stimulate platelet aggregation (ADP, collagen, or arachidonic acid), the tests determine the percent aggregation or inhibition of functional platelets. Manufacturer reference ranges, determined by testing blood samples from healthy volunteers, are 86-100% for ADP, 70-100% for collagen, and 60-100% for arachidonic acid. Values within these ranges indicate 'normal (positive)' platelet aggregation, which is important for clotting; lower values may be considered 'abnormal (negative)' and reflective of platelet inhibition. The manufacturer advises each laboratory to establish their own reference ranges for their patient population.
Time frame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration
Population: The analysis of absolute change included all patients who had coagulation parameter data available at both pre- and post-IMP time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octaplex | Comparison of the Effect of Octaplex Versus FP Administration on the Change in Platelet Function Measured by Plateletworks | -5.9 percentage | Standard Deviation 10.34 |
| Frozen Plasma | Comparison of the Effect of Octaplex Versus FP Administration on the Change in Platelet Function Measured by Plateletworks | -18.2 percentage | Standard Deviation 17.72 |
p-value: 0.065895% CI: [-0.87, 25.38]ANOVA
Secondary
Comparison of the Effect of Octaplex Versus FP Administration on the Change in Prothrombin Time (PT)
The prothrombin time (PT) measures the time it takes for clotting to occur, primarily assessing the extrinsic pathway of the coagulation cascade. Normal PT values range from 9 to 13 seconds. Higher PT values indicate a prolonged clotting time, suggesting potential issues with clotting factors such as fibrinogen, factors V, VII, and X and prothrombin, and are associated with bleeding. Effective procoagulant therapy can reduce/normalize the PT.
Time frame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octaplex | Comparison of the Effect of Octaplex Versus FP Administration on the Change in Prothrombin Time (PT) | -10.3 seconds | Standard Deviation 20.9 |
| Frozen Plasma | Comparison of the Effect of Octaplex Versus FP Administration on the Change in Prothrombin Time (PT) | -0.7 seconds | — |
p-value: 0.673595% CI: [-60.45, 41.18]ANOVA
Secondary
Comparison of the Effect of Octaplex Versus FP Administration on the Change in ROTEM EXTEM CT
A rotational thromboelastometry (ROTEM; Werfen) device can be used at the bedside to rapidly assess the patient's coagulation status. Different viscoelastic tests can be performed to assess the dynamics of clot formation and lysis. Specifically, the EXTEM test is activated with tissue factor and evaluates the extrinsic coagulation pathway, with clotting time (CT) providing a measure (in seconds) of how quickly a clot starts forming. Prolonged EXTEM CT is associated with bleeding. Effective procoagulant therapy can reduce/normalize the EXTEM CT.
Time frame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration
Population: Few data were available as ROTEM measurements were not mandated by the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octaplex | Comparison of the Effect of Octaplex Versus FP Administration on the Change in ROTEM EXTEM CT | -21.5 seconds | Standard Deviation 18 |
| Frozen Plasma | Comparison of the Effect of Octaplex Versus FP Administration on the Change in ROTEM EXTEM CT | -21.7 seconds | Standard Deviation 18.65 |
p-value: 0.969895% CI: [-14.78, 15.34]ANOVA
Secondary
Comparison of the Effect of Octaplex Versus FP Administration on the Change in ROTEM EXTEM MCF
A rotational thromboelastometry (ROTEM; Werfen) device can be used at the bedside to rapidly assess the patient's coagulation status. Different viscoelastic tests can be performed to assess the dynamics of clot formation and lysis. Specifically, the EXTEM test is activated with tissue factor and evaluates the extrinsic coagulation pathway, with maximum clot firmness (MCF) providing a measure (in mm) of the strength of the clot. Reduced EXTEM MCF is associated with bleeding. Effective procoagulant therapy can increase/normalize the EXTEM MCF.
Time frame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration
Population: Few data were available as ROTEM measurements were not mandated by the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octaplex | Comparison of the Effect of Octaplex Versus FP Administration on the Change in ROTEM EXTEM MCF | 3.6 Millimeters (mm) | Standard Deviation 4.95 |
| Frozen Plasma | Comparison of the Effect of Octaplex Versus FP Administration on the Change in ROTEM EXTEM MCF | 6.7 Millimeters (mm) | Standard Deviation 9.54 |
p-value: 0.336395% CI: [-9.61, 3.42]ANOVA
Secondary
Comparison of the Effect of Octaplex Versus FP Administration on the Change in ROTEM FIBTEM MCF
A rotational thromboelastometry (ROTEM; Werfen) device can be used at the bedside to rapidly assess the patient's coagulation status. Different viscoelastic tests can be performed to assess the dynamics of clot formation and lysis. Specifically, the FIBTEM test evaluates fibrin-based clotting - it is extrinsically activated with tissue factor and additionally incorporates an inhibitor to eliminate the contribution of platelets to clotting. Maximum clot firmness (MCF) in the FIBTEM test provides a measure (in mm) of the strength of the fibrin-based clot. Reduced FIBTEM MCF is associated with bleeding. Effective procoagulant therapy to restore fibrinogen can increase/normalize the FIBTEM MCF.
Time frame: Within 75 minutes before to within 75 minutes after the initiation of IMP administration
Population: Few data were available as ROTEM measurements were not mandated by the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Octaplex | Comparison of the Effect of Octaplex Versus FP Administration on the Change in ROTEM FIBTEM MCF | 3.8 Millimeters (mm) | Standard Deviation 2.75 |
| Frozen Plasma | Comparison of the Effect of Octaplex Versus FP Administration on the Change in ROTEM FIBTEM MCF | 1.4 Millimeters (mm) | Standard Deviation 13.78 |
p-value: 0.573695% CI: [-6.33, 11.16]ANOVA
Secondary
Comparison of the Incidence of Death Between Octaplex and FP Groups
Time frame: Up to 30 days after the end of CPB
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Octaplex | Comparison of the Incidence of Death Between Octaplex and FP Groups | 7 Participants |
| Frozen Plasma | Comparison of the Incidence of Death Between Octaplex and FP Groups | 8 Participants |
p-value: 0.749795% CI: [0.4211, 3.3235]Regression, Logistic
Secondary
Comparison of the Number of Days Alive and Out of Hospital Between Octaplex and FP Groups
Time frame: From the beginning of surgery up to postoperative day 30
Population: One participant is excluded from analysis due to missing start/end date of hospitalization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Octaplex | Comparison of the Number of Days Alive and Out of Hospital Between Octaplex and FP Groups | 21.0 days |
| Frozen Plasma | Comparison of the Number of Days Alive and Out of Hospital Between Octaplex and FP Groups | 21.0 days |
Secondary
Comparison of Total Time Elapsed From Initiation of the First Dose of IMP to Arrival Into the ICU Between the Octaplex and FP Groups.
Time frame: From initiation of IMP to arrival at ICU room (within 24 hours)
Population: 37 patients were excluded from the analysis population. 27 (12 in the Octaplex group, 25 in the FP group) who were already in the ICU when the first dose of IMP was initiated, 5 patients (2 in the Octaplex group, 3 in the FP group) for whom the time intervals could not be calculated due to incomplete date/time of arrival at ICU, and 1 patient (FP group) who was not in the ICU, therefore the time interval could not be calculated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Octaplex | Comparison of Total Time Elapsed From Initiation of the First Dose of IMP to Arrival Into the ICU Between the Octaplex and FP Groups. | 1.0 hours |
| Frozen Plasma | Comparison of Total Time Elapsed From Initiation of the First Dose of IMP to Arrival Into the ICU Between the Octaplex and FP Groups. | 1.2 hours |
p-value: 0.072695% CI: [-0.4, 0.02]ANOVA