Reversal of Coagulopathy
Conditions
Keywords
Anticoagulant reversal, Prothrombin Complex Concentrate, Coagulopathy, Coumarin derivatives, Emergency surgery, Invasive procedures, Vitamin K, Reversal of coagulopathy induced by coumarin derivatives, Kcentra
Brief summary
The purpose of this study is to evaluate efficacy, safety and tolerance of Beriplex® P/N (Kcentra) compared with plasma in regard to rapid reversal of coagulopathy induced by vitamin K antagonists in subjects who require immediate correction of international normalized ratio (INR) because of emergency surgery.
Interventions
BIOLOGICALBeriplex® P/N (Kcentra)
Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body-weight.
BIOLOGICALFresh frozen plasma
Intravenous infusion, dosage depending on baseline INR and body weight
Sponsors
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female subjects greater than or equal to 18 years, * Subjects currently on oral vitamin K antagonist (VKA) therapy, * An urgent surgical procedure is required within 24 hours of the start of investigational medicinal product (IMP), * Due to the nature of the procedure, withdrawal of oral VKA therapy and infusion of plasma are also indicated to reverse the VKA effect, * INR greater than or equal to 2 within 3 hours before start of IMP, * Informed consent has been obtained.
Exclusion criteria
* Subjects requiring urgent surgical procedures where according to the surgeon's clinical judgment, an accurate estimate of blood loss is not possible (e.g., ruptured aneurysm), * Subjects for whom administration of intravenous vitamin K and vitamin K antagonists withdrawal alone can adequately correct the subject's coagulopathy before initiation of the urgent surgical procedure, * Administration of intravenous vitamin K more than 3 hours or administration of oral vitamin K more than 6 hours prior to infusion of IMP, * Subjects in whom lowering INR within normal range may present an unacceptable risk for a thromboembolic complication where the INR goal is to lower but not normalize the INR because of risk of a procedure-associated stroke, * Subjects, who despite medical management that includes close monitoring and diuretics, may not, by investigator assessment, tolerate the total volume of IMP required by the protocol, * Expected need for additional non-study blood products before infusion of IMP (Note: Administration of packed red blood cells is not an exclusion criterion), * Expected need for platelet transfusions or desmopressin before Day 10, * Acute trauma for which reversal of vitamin K antagonists alone would not be expected to control or resolve an acute bleeding complication and/or control the acute bleeding event, * Unfractionated or low molecular weight heparin use within 24 hours before randomization or potential need before completion of the procedure, * History of thromboembolic event, myocardial infarction, unstable angina pectoris, critical aortic stenosis, cerebral vascular accident, transient ischemic attack, severe peripheral vascular disease, disseminated intravascular coagulation within 3 months of enrollment, * Reversal of VKA therapy alone may not resolve the coagulopathy (eg, receiving a potent anti-platelet agent, i.e., clopidogrel or prasugrel, or advanced liver disease), * Known history of antiphospholipid antibody syndrome or lupus anticoagulant antibodies, * Suspected or confirmed serious viral or bacterial infection, e.g., meningitis, or sepsis at time of enrollment, * Administration of whole blood, plasma, plasma fractions or platelets within 2 weeks prior to inclusion into the study (Note: Administration of packed red blood cells is not an exclusion criterion), * Pre-existing progressive fatal disease with a life expectancy of less than 2 months, * Known inhibitors to coagulation factors II, VII, IX, or X; or hereditary protein C or protein S deficiency; or heparin-induced, type II thrombocytopenia, * Treatment with any other investigational medicinal product within 30 days prior to inclusion into the study, * Presence or history of hypersensitivity to components of the study medication, * Pregnant or breast-feeding women, * Prior inclusion in this study or any other CSL Behring sponsored Beriplex study, * For subjects with intracranial hemorrhage with: * Glasgow Coma Score \<10 (see Appendix 8) * Modified Rankin Score \> 3 prior to ICH (see Appendix 9) * Intracerebral hemorrhage * Epidural hematomas * Infratentorial hemorrhage * Subarachnoid hemorrhage (SAH) subjects with a Hunt and Hess Scale \>2 * Subdural hematomas that: * are judged to be an acute subdural hematoma (based on neurosurgeon review) * have a concurrent SAH or parenchymal contusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Hemostatic Efficacy During Surgery | From the start of infusion until the end of surgery | Hemostatic efficacy was rated as excellent, good, or poor/none, based on prespecified definitions. Hemostatic efficacy was the binary endpoint of effective or non-effective hemostasis, where 'effective' was a hemostatic efficacy rating of excellent or good, and 'non-effective' was a hemostatic efficacy rating of poor/none. |
| Percentage of Participants Who Had a Rapid Decrease of the INR | 30 minutes after the end of infusion | A rapid decrease of the INR was defined as an INR ≤ 1.3 at 30 minutes after the end of infusion. The INR is a standard way to describe the time it takes for blood to clot; an INR range of 0.8 to 1.2 is considered normal for a healthy person who is not using oral anticoagulant therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With INR Correction at Various Times After the Start of Infusion | From the start of infusion until INR correction; calculated at 0.5, 1, 3, 6, 12, and 24 h after the start of infusion | The time taken from the start of infusion to INR correction (defined as an INR ≤ 1.3) was recorded. The percentage of participants with INR correction was calculated at 0.5, 1, 3, 6, 12, and 24 h after the start of infusion. |
| Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | From pre-infusion until 24 h after the start of infusion | Plasma levels are presented as the percentage of normal at pre-infusion and 30 min and 24 h after the start of infusion. The plasma level assay results are reported as a potency relative to a standard, where 100% is considered to be normal. |
| Overall Treatment-emergent Adverse Events (TEAEs) | From the start of infusion up to the allowed time window of the Day 10 visit for non-serious AEs and from the start of infusion up to the allowed time window of the Day 45 visit for SAEs | Number of participants with TEAEs. TEAEs were defined as adverse events that developed or worsened following exposure to investigational medicinal product. Treatment-related TEAEs were events whose relationship to study treatment was related, probably related, or possibly related in the opinion of the investigator. Treatment emergent adverse events with missing relationship were considered related to treatment. Serious TEAEs were treatment-emergent serious adverse events (SAEs). |
| Percentage of Participants Who Received Red Blood Cells | From the start of surgery until 24 h after the start of surgery | Red blood cells were PRBCs and whole blood |
| Transfusion of Packed Red Blood Cells (PRBCs) or Whole Blood | From the start of surgery until 24 h after the start of surgery | The total units of transfused PRBCs or whole blood |
Countries
Belarus, Bulgaria, Lebanon, Romania, Russia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Beriplex® P/N Beriplex® P/N: Intravenous infusion, dosage depending on baseline INR, amount of coagulation factor IX and body-weight. | 87 |
| Fresh Frozen Plasma Fresh frozen plasma: Intravenous infusion, dosage depending on baseline INR and body weight | 81 |
| Total | 168 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death / Serious Adverse Event | 4 | 6 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Patient did not attend scheduled visit | 2 | 1 |
| Overall Study | Patient did not have surgery | 1 | 1 |
| Overall Study | Patient died outside SAE report period | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 7 |
| Overall Study | Surgery finished outside protocol window | 1 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 4 |
Baseline characteristics
| Characteristic | Beriplex® P/N | Fresh Frozen Plasma | Total |
|---|---|---|---|
| Age, Customized >= 65 to < 75 years | 21 participants | 19 participants | 40 participants |
| Age, Customized < 65 years | 32 participants | 39 participants | 71 participants |
| Age, Customized >= 75 years | 34 participants | 23 participants | 57 participants |
| Sex: Female, Male Female | 37 Participants | 31 Participants | 68 Participants |
| Sex: Female, Male Male | 50 Participants | 50 Participants | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 41 / 88 | 44 / 88 |
| serious Total, serious adverse events | 22 / 88 | 23 / 88 |
Outcome results
Primary
Percentage of Participants Achieving Hemostatic Efficacy During Surgery
Hemostatic efficacy was rated as excellent, good, or poor/none, based on prespecified definitions. Hemostatic efficacy was the binary endpoint of effective or non-effective hemostasis, where 'effective' was a hemostatic efficacy rating of excellent or good, and 'non-effective' was a hemostatic efficacy rating of poor/none.
Time frame: From the start of infusion until the end of surgery
Population: The Intention-to-Treat Efficacy ITT-E population included all randomized participants who had received any study product, underwent the intended surgical procedure, and had an INR \> 1.3 prior to the infusion. Participants in the ITT-E population were analyzed 'as randomized'.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Beriplex® P/N | Percentage of Participants Achieving Hemostatic Efficacy During Surgery | 89.7 percentage of participants |
| Fresh Frozen Plasma | Percentage of Participants Achieving Hemostatic Efficacy During Surgery | 75.3 percentage of participants |
Comparison: The analysis of hemostatic efficacy was via calculation of the 95% confidence interval (CI) for the difference (Beriplex minus plasma) in the percentage of participants with effective hemostasis.95% CI: [2.8, 25.8]95% confidence interval
Primary
Percentage of Participants Who Had a Rapid Decrease of the INR
A rapid decrease of the INR was defined as an INR ≤ 1.3 at 30 minutes after the end of infusion. The INR is a standard way to describe the time it takes for blood to clot; an INR range of 0.8 to 1.2 is considered normal for a healthy person who is not using oral anticoagulant therapy.
Time frame: 30 minutes after the end of infusion
Population: The ITT-E population included all randomized participants who had received any study product, underwent the intended surgical procedure, and had an international normalized ratio INR \> 1.3 prior to the infusion. Participants in the ITT-E population were analyzed 'as randomized'.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Beriplex® P/N | Percentage of Participants Who Had a Rapid Decrease of the INR | 55.2 percentage of participants |
| Fresh Frozen Plasma | Percentage of Participants Who Had a Rapid Decrease of the INR | 9.9 percentage of participants |
Comparison: The analysis of rapid decrease of the INR was via calculation of the 95% CI for the difference (Beriplex minus plasma) in the percentage of participants with INR ≤ 1.3 at 30 minutes after the end of infusion.95% CI: [31.9, 56.4]Newcombe-Wilson score method
Secondary
Overall Treatment-emergent Adverse Events (TEAEs)
Number of participants with TEAEs. TEAEs were defined as adverse events that developed or worsened following exposure to investigational medicinal product. Treatment-related TEAEs were events whose relationship to study treatment was related, probably related, or possibly related in the opinion of the investigator. Treatment emergent adverse events with missing relationship were considered related to treatment. Serious TEAEs were treatment-emergent serious adverse events (SAEs).
Time frame: From the start of infusion up to the allowed time window of the Day 10 visit for non-serious AEs and from the start of infusion up to the allowed time window of the Day 45 visit for SAEs
Population: The Intention-to-Treat Safety (ITT-S) population included all participants who were randomized and who had received any portion of study product. Participants in the ITT-S population were analyzed 'as treated'.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Beriplex® P/N | Overall Treatment-emergent Adverse Events (TEAEs) | Serious TEAE | 22 participants |
| Beriplex® P/N | Overall Treatment-emergent Adverse Events (TEAEs) | Death | 4 participants |
| Beriplex® P/N | Overall Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 49 participants |
| Beriplex® P/N | Overall Treatment-emergent Adverse Events (TEAEs) | At least possibly treatment-related TEAE | 8 participants |
| Fresh Frozen Plasma | Overall Treatment-emergent Adverse Events (TEAEs) | At least possibly treatment-related TEAE | 15 participants |
| Fresh Frozen Plasma | Overall Treatment-emergent Adverse Events (TEAEs) | Serious TEAE | 23 participants |
| Fresh Frozen Plasma | Overall Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 53 participants |
| Fresh Frozen Plasma | Overall Treatment-emergent Adverse Events (TEAEs) | Death | 8 participants |
Secondary
Percentage of Participants Who Received Red Blood Cells
Red blood cells were PRBCs and whole blood
Time frame: From the start of surgery until 24 h after the start of surgery
Population: The ITT-E population included all randomized participants who had received any study product, underwent the intended surgical procedure, and had an international normalized ratio INR \> 1.3 prior to the infusion. Participants in the ITT-E population were analyzed 'as randomized'.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Beriplex® P/N | Percentage of Participants Who Received Red Blood Cells | 16.1 percentage of participants |
| Fresh Frozen Plasma | Percentage of Participants Who Received Red Blood Cells | 14.8 percentage of participants |
Secondary
Percentage of Participants With INR Correction at Various Times After the Start of Infusion
The time taken from the start of infusion to INR correction (defined as an INR ≤ 1.3) was recorded. The percentage of participants with INR correction was calculated at 0.5, 1, 3, 6, 12, and 24 h after the start of infusion.
Time frame: From the start of infusion until INR correction; calculated at 0.5, 1, 3, 6, 12, and 24 h after the start of infusion
Population: The ITT-E population included all randomized participants who had received any study product, underwent the intended surgical procedure, and had an international normalized ratio INR \> 1.3 prior to the infusion. Participants in the ITT-E population were analyzed 'as randomized'.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Beriplex® P/N | Percentage of Participants With INR Correction at Various Times After the Start of Infusion | 0.5 h | 1 percentage of participants |
| Beriplex® P/N | Percentage of Participants With INR Correction at Various Times After the Start of Infusion | 1 h | 54 percentage of participants |
| Beriplex® P/N | Percentage of Participants With INR Correction at Various Times After the Start of Infusion | 3 h | 77 percentage of participants |
| Beriplex® P/N | Percentage of Participants With INR Correction at Various Times After the Start of Infusion | 6 h | 81 percentage of participants |
| Beriplex® P/N | Percentage of Participants With INR Correction at Various Times After the Start of Infusion | 12 h | 83 percentage of participants |
| Beriplex® P/N | Percentage of Participants With INR Correction at Various Times After the Start of Infusion | 24 h | 87 percentage of participants |
| Fresh Frozen Plasma | Percentage of Participants With INR Correction at Various Times After the Start of Infusion | 12 h | 32 percentage of participants |
| Fresh Frozen Plasma | Percentage of Participants With INR Correction at Various Times After the Start of Infusion | 0.5 h | 0 percentage of participants |
| Fresh Frozen Plasma | Percentage of Participants With INR Correction at Various Times After the Start of Infusion | 6 h | 20 percentage of participants |
| Fresh Frozen Plasma | Percentage of Participants With INR Correction at Various Times After the Start of Infusion | 1 h | 0 percentage of participants |
| Fresh Frozen Plasma | Percentage of Participants With INR Correction at Various Times After the Start of Infusion | 24 h | 48 percentage of participants |
| Fresh Frozen Plasma | Percentage of Participants With INR Correction at Various Times After the Start of Infusion | 3 h | 10 percentage of participants |
Secondary
Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S
Plasma levels are presented as the percentage of normal at pre-infusion and 30 min and 24 h after the start of infusion. The plasma level assay results are reported as a potency relative to a standard, where 100% is considered to be normal.
Time frame: From pre-infusion until 24 h after the start of infusion
Population: The ITT-E population included all randomized participants who had received any study product, underwent the intended surgical procedure, and had an international normalized ratio INR \> 1.3 prior to the infusion. Participants in the ITT-E population were analyzed 'as randomized'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Beriplex® P/N | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor II, pre-infusion (n = 85; 79) | 32.0 percentage of normal | Standard Deviation 19.93 |
| Beriplex® P/N | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor II, 0.5 h after infusion start (n = 71; 73) | 84.5 percentage of normal | Standard Deviation 20.92 |
| Beriplex® P/N | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor II, 24 h after infusion start (n = 81; 74) | 81.4 percentage of normal | Standard Deviation 24.83 |
| Beriplex® P/N | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor VII, pre-infusion start (n = 85; 79) | 36.8 percentage of normal | Standard Deviation 59.27 |
| Beriplex® P/N | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor VII, 0.5h after infusion start (n = 71; 73) | 60.1 percentage of normal | Standard Deviation 44.91 |
| Beriplex® P/N | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor VII, 24 h after infusion start (n = 81; 74) | 85.5 percentage of normal | Standard Deviation 59.76 |
| Beriplex® P/N | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor IX, pre-infusion (n = 85; 79) | 48.1 percentage of normal | Standard Deviation 25.62 |
| Beriplex® P/N | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor IX, 0.5 h after infusion start (n = 71; 73) | 71.6 percentage of normal | Standard Deviation 25.38 |
| Beriplex® P/N | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor IX, 24 h after infusion start (n = 81; 74) | 85.2 percentage of normal | Standard Deviation 33.39 |
| Beriplex® P/N | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor X, pre-infusion (n = 85; 79) | 19.3 percentage of normal | Standard Deviation 19.32 |
| Beriplex® P/N | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor X, 0.5 h after infusion start (n = 71; 73) | 82.3 percentage of normal | Standard Deviation 23.33 |
| Beriplex® P/N | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor X, 24 h after infusion start (n = 81; 74) | 78.3 percentage of normal | Standard Deviation 25.62 |
| Beriplex® P/N | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Protein C, pre-infusion (n = 85; 78) | 48.8 percentage of normal | Standard Deviation 19.07 |
| Beriplex® P/N | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Protein C, 0.5 h after infusion start (n = 71; 73) | 97.1 percentage of normal | Standard Deviation 21.97 |
| Beriplex® P/N | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Protein C, 24 h after infusion start (n = 81; 74) | 87.3 percentage of normal | Standard Deviation 26.28 |
| Beriplex® P/N | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Protein S, pre-infusion (n = 85; 79) | 45.25 percentage of normal | Standard Deviation 18.498 |
| Beriplex® P/N | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Protein S, 0.5 h after infusion start (n = 72; 73) | 80.73 percentage of normal | Standard Deviation 31.489 |
| Beriplex® P/N | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Protein S, 24 h after infusion start (n = 82; 74) | 75.97 percentage of normal | Standard Deviation 36.449 |
| Fresh Frozen Plasma | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Protein C, 0.5 h after infusion start (n = 71; 73) | 52.5 percentage of normal | Standard Deviation 18.69 |
| Fresh Frozen Plasma | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor II, pre-infusion (n = 85; 79) | 34.8 percentage of normal | Standard Deviation 26.19 |
| Fresh Frozen Plasma | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor X, pre-infusion (n = 85; 79) | 20.8 percentage of normal | Standard Deviation 21.38 |
| Fresh Frozen Plasma | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor II, 0.5 h after infusion start (n = 71; 73) | 42.5 percentage of normal | Standard Deviation 25.71 |
| Fresh Frozen Plasma | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Protein S, 24 h after infusion start (n = 82; 74) | 69.32 percentage of normal | Standard Deviation 27.504 |
| Fresh Frozen Plasma | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor II, 24 h after infusion start (n = 81; 74) | 65.6 percentage of normal | Standard Deviation 23.68 |
| Fresh Frozen Plasma | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor X, 0.5 h after infusion start (n = 71; 73) | 29.8 percentage of normal | Standard Deviation 22.51 |
| Fresh Frozen Plasma | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor VII, pre-infusion start (n = 85; 79) | 31.1 percentage of normal | Standard Deviation 25.16 |
| Fresh Frozen Plasma | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Protein C, 24 h after infusion start (n = 81; 74) | 78.1 percentage of normal | Standard Deviation 24.8 |
| Fresh Frozen Plasma | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor VII, 0.5h after infusion start (n = 71; 73) | 41.6 percentage of normal | Standard Deviation 42.9 |
| Fresh Frozen Plasma | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor X, 24 h after infusion start (n = 81; 74) | 60.2 percentage of normal | Standard Deviation 22.44 |
| Fresh Frozen Plasma | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor VII, 24 h after infusion start (n = 81; 74) | 83.7 percentage of normal | Standard Deviation 58.9 |
| Fresh Frozen Plasma | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Protein S, 0.5 h after infusion start (n = 72; 73) | 55.82 percentage of normal | Standard Deviation 24.689 |
| Fresh Frozen Plasma | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor IX, pre-infusion (n = 85; 79) | 55.8 percentage of normal | Standard Deviation 30.5 |
| Fresh Frozen Plasma | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Protein C, pre-infusion (n = 85; 78) | 47.6 percentage of normal | Standard Deviation 21.38 |
| Fresh Frozen Plasma | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor IX, 0.5 h after infusion start (n = 71; 73) | 56.2 percentage of normal | Standard Deviation 23.12 |
| Fresh Frozen Plasma | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Protein S, pre-infusion (n = 85; 79) | 46.18 percentage of normal | Standard Deviation 20.986 |
| Fresh Frozen Plasma | Plasma Levels of Factors II, VII, IX, and X, Protein C, and Protein S | Factor IX, 24 h after infusion start (n = 81; 74) | 93.7 percentage of normal | Standard Deviation 34.25 |
Secondary
Transfusion of Packed Red Blood Cells (PRBCs) or Whole Blood
The total units of transfused PRBCs or whole blood
Time frame: From the start of surgery until 24 h after the start of surgery
Population: The ITT-E population included all randomized participants who had received any study product, underwent the intended surgical procedure, and had an international normalized ratio INR \> 1.3 prior to the infusion. Participants in the ITT-E population were analyzed 'as randomized'.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Beriplex® P/N | Transfusion of Packed Red Blood Cells (PRBCs) or Whole Blood | 0.3 units of PRBCs or whole blood | Standard Deviation 0.9 |
| Fresh Frozen Plasma | Transfusion of Packed Red Blood Cells (PRBCs) or Whole Blood | 0.4 units of PRBCs or whole blood | Standard Deviation 1.02 |