Bleeding Disorder, Hypofibrinogenemia; Acquired
Conditions
Keywords
Fibrinogen
Brief summary
The main purpose of this study was to demonstrate the efficacy and safety of intraoperative use of fibrinogen concentrate BT524, as a complementary therapy for the management of uncontrolled severe hemorrhage in acquired hypofibrinogenemia. This non-inferiority study focused on the primary objective of demonstrating that BT524 is non-inferior that means not worse than the comparator fresh frozen plasma/cryoprecipitate in reducing intraoperative blood loss when administered intravenously in subjects with acquired hypofibrinogenemia undergoing elective major spinal or abdominal surgery.
Detailed description
Fibrinogen is the first coagulation factor to become critically reduced during intraoperative bleeding. Therefore, rapid supplementation of fibrinogen to restore physiological plasma levels is an important component in achieving and maintaining hemostasis in bleeding patients. In this study, subjects with major blood loss during elective spinal surgery or abdominal surgery were randomized to receive either intravenous transfusion of the fibrinogen concentrate BT524, or fibrinogen-containing fresh frozen plasma/cryoprecipitate as first hemostatic intervention to rapidly replenish fibrinogen and control bleeding.
Interventions
BIOLOGICALBT524
BT524 was administered intravenously at a patient specific dosage depending on the type of surgery, the extent of bleeding and the subject's clinical condition.
BIOLOGICALFFP/Cryo
FFP/Cryo was administered intravenously; dosage according to local standards. FFP, 15 mL per kg body weight (BW); Cryoprecipitate, fixed dose of 10 units.
Sponsors
PRA Health Sciences
ICON Clinical Research
Biotest
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Study 995 was partially blinded; surgeon, surgical staff and subjects were blinded to treatment allocation throughout the entire surgery. The subject was blinded throughout the study. The Investigational Medicinal Product (IMP), BT524 or FFP/Cryo, was administered by an unblinded anaesthesiologist.
Intervention model description
Patients were randomly assigned to treatment with BT524 or FFP/Cryo.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
At screening: 1. Written informed consent 2. Subjects scheduled for elective major spinal surgery or cytoreductive pseudomyxoma peritonei (PMP) surgery with expected major blood loss 3. Male or female, aged ≥ 18 years 4. No increased bleeding risk as assessed by standard coagulation tests and medical history Intra-operative: 5\. 1. Subjects who underwent spinal surgery: Intra-operative clinically relevant bleeding of approximately 1 Liter, requiring hemostatic treatment during surgery. 2. Subjects who underwent cytoreductive PMP surgery: Intra-operative prediction of clinically relevant bleeding of more than 2 Liter, requiring hemostatic treatment during surgery
Exclusion criteria
1. Pregnancy or unreliable contraceptive measures or breast feeding (women only) 2. Hypersensitivity to proteins of human origin or known hypersensitivity reactions to components of the Investigational Medicinal Products (IMP) 3. Participation in another clinical study within 30 days before entering the study or during the study and/or previous participation in this study 4. Treatment with any fibrinogen concentrate and/or fibrinogen-containing product within 30 days prior to infusion of IMP 5. Employee or direct relative of an employee of the Contract Research Organization (CRO), the study site, or Biotest 6. Inability or lacking motivation to participate in the study 7. Medical condition, laboratory finding (e.g., clinically relevant biochemical or hematological findings outside the normal range), or physical exam finding that in the opinion of the investigator precludes participation 8. Presence or history of venous/arterial thrombosis or thromboembolic event (TEE) in the preceding 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intra-operative Blood Loss | From decision to treat the subject with IMP until end of surgery, an average of 5 hours | Intra-operative blood loss as measured by amount of blood from blood suction unit and amount of blood from surgical cloths and compresses. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Successful Correction of Fibrinogen Level | prior 1st dose, pre-dose, 15 minutes and 90 minutes after start of first IMP administration, end of surgery | Correction of the fibrinogen level, measured via thromboelastometry (ROTEM/FIBTEM A10), within 15 minutes after IMP start, between 15 and 90 minutes after IMP start, after 90 minutes after IMP start, or unsuccessful correction. The 4 categories were compared between the two treatment arms using a Chi-square test. |
| Transfusion Requirements: Cell Salvage | After start of first IMP administration until end of surgery, an average of 5 hours | Total amount of transfusion products (allogeneic blood products) or autologous blood transfusion infused after start of first IMP administration until end of surgery. The end of surgery is defined as time of last suture. |
| Transfusion Requirements: Allogeneic Platelets | After start of first IMP administration until end of surgery, an average of 5 hours | Total amount of transfusion products (allogeneic blood products) or autologous blood transfusion infused after start of first IMP administration until end of surgery. The end of surgery is defined as time of last suture. |
| Transfusion Requirements: Allogeneic Red Blood Cells | After start of first IMP administration until end of surgery, an average of 5 hours | Total amount of transfusion products (allogeneic blood products) or autologous blood transfusion infused after start of first IMP administration until end of surgery. The end of surgery is defined as time of last suture. |
| Transfusion Requirements: Fresh Frozen Plasma | After start of first IMP administration until end of surgery, an average of 5 hours | Total amount of transfusion products (allogeneic blood products) or autologous blood transfusion infused after start of first IMP administration until end of surgery. The end of surgery is defined as time of last suture. |
| Transfusion Requirements, Cryoprecipitate | After start of first IMP administration until end of surgery, an average of 5 hours | Total amount of transfusion products (allogeneic blood products) or autologous blood transfusion infused after start of first IMP administration until end of surgery. The end of surgery is defined as time of last suture. |
| Proportion (%) of Subjects With Successful Correction of Fibrinogen Level (FIBTEM A10) 15 Minutes After Start of First IMP Administration | Prior first dose, 15 minutes after start of first IMP administration | Successful correction of the fibrinogen level is defined as restoring fibrinogen FIBTEM A10 baseline (prior surgery) levels measured by ROTEM (thromboelastometry) 15 minutes after start of first IMP administration |
| Post-operative Blood Loss | From end of surgery (time of last suture) up to 24 hours after the end of surgery | Post-operative drainage volume in the first 24 hours after end of surgery |
| Subjects With Rebleeds | End of surgery up to 8 days after surgery | Proportion (%) of subjects with rebleeds after the end of surgery until day 8 |
| Hospital Length of Stay After Surgery | From day of surgery until day of hospital discharge, an average of 16 days (up to 56 days) | Length of stay after surgery (days) = 'date of hospital discharge' minus 'date of surgery'. Where date of discharge is the date of discharge following the IMP treated surgery. |
| In-hospital Mortality | From day of surgery until day of hospital discharge, an average of 16 days (up to 56 days) | Number and percentages of subjects who died during hospital stay |
| Number of Subjects With Thrombosis or Thromboembolic Events (TEEs) | From day of surgery until closing visit (up to 181 days) | Total number of subjects with thrombosis or TEEs documented as treatment-emergent adverse events of special interest |
| Change in Viral Status | Screening visit (up to 42 days prior to surgery) and closing visit (up to 181 days after surgery) | Number of subjects with change in status of viral infections |
| Amount of Red Blood Cells (RBCs) | After start of first IMP administration until end of surgery, an average of 5 hours | Amount (volume) of RBCs (allogenic and autologous RBCs) infused after start of first IMP administration until end of surgery. The end of surgery is defined as time of last suture. |
Countries
Belgium, Czechia, Germany, Poland, Spain, Switzerland, United Kingdom
Participant flow
Recruitment details
339 subjects were screened, of these 222 subjects were eligible for the study and randomized. Baseline characteristics are available for the 222 randomized subjects.
Pre-assignment details
There were 117 screen failures due to the following reasons: Eligibility criteria not met (before surgery), n=11; Intra-operative eligibility criterion not met, n=69; Physician decision, n=21; Adverse event, n=2; Withdrawal by subject, n=10; Technical reason, n=3; Other, n=1. Subjects eligible for randomization: n=222.
Participants by arm
| Arm | Count |
|---|---|
| BT524 Investigational Human Fibrinogen Concentrate
BT524: BT524 was administered intravenously at a patient specific dosage depending on the type of surgery, the extent of bleeding and the subject's clinical condition. | 110 |
| FFP/Cryo Standard of Care
Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo): FFP/Cryo was administered intravenously; dosage according to local standards. FFP, 15 mL per kg BW; Cryo, fixed dose of 10 units. | 112 |
| Total | 222 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Trial Compliance | 1 | 1 |
| Overall Study | Lost to Follow-up | 4 | 2 |
| Overall Study | Physical disability to come to the site for the closing visit | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | FFP/Cryo | Total | BT524 |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 54 Participants | 102 Participants | 48 Participants |
| Age, Categorical Between 18 and 65 years | 58 Participants | 120 Participants | 62 Participants |
| Age, Continuous | 60.8 years STANDARD_DEVIATION 14.07 | 61.0 years STANDARD_DEVIATION 13.29 | 61.2 years STANDARD_DEVIATION 12.52 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 12 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 106 Participants | 209 Participants | 103 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Expected Blood Loss >1000 mL to <=2000 mL | 48 participants | 92 participants | 44 participants |
| Expected Blood Loss >2000 mL | 64 participants | 130 participants | 66 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 107 Participants | 216 Participants | 109 Participants |
| Region of Enrollment Czechia | 30 participants | 58 participants | 28 participants |
| Region of Enrollment Germany | 9 participants | 23 participants | 14 participants |
| Region of Enrollment Poland | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Spain | 13 participants | 24 participants | 11 participants |
| Region of Enrollment Switzerland | 9 participants | 18 participants | 9 participants |
| Region of Enrollment United Kingdom | 50 participants | 98 participants | 48 participants |
| Sex: Female, Male Female | 64 Participants | 131 Participants | 67 Participants |
| Sex: Female, Male Male | 48 Participants | 91 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 110 | 1 / 112 |
| other Total, other adverse events | 92 / 110 | 93 / 112 |
| serious Total, serious adverse events | 28 / 110 | 41 / 112 |
Outcome results
Primary
Intra-operative Blood Loss
Intra-operative blood loss as measured by amount of blood from blood suction unit and amount of blood from surgical cloths and compresses.
Time frame: From decision to treat the subject with IMP until end of surgery, an average of 5 hours
Population: Per-protocol set (PPS): All randomized subjects receiving IMP post randomization and with data collected post randomization. Subjects who were compliant with the trial protocol without any major protocol deviations thought to have the potential to impact the results of the efficacy analysis, e.g., no treatment or incomplete treatment with study intervention (BT524 or FFP/Cryo) during surgery, no postdose efficacy assessment for the primary endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BT524 | Intra-operative Blood Loss | 1380.7 mL |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Intra-operative Blood Loss | 1660.13 mL |
p-value: <0.00195% CI: [-552.38, -6.48]Van Elteren test
Secondary
Amount of Red Blood Cells (RBCs)
Amount (volume) of RBCs (allogenic and autologous RBCs) infused after start of first IMP administration until end of surgery. The end of surgery is defined as time of last suture.
Time frame: After start of first IMP administration until end of surgery, an average of 5 hours
Population: Modified Full Analysis Set (mFAS): All randomized subjects who received at least one dose of IMP prior to the 'end of surgery' and have at least one postdose efficacy assessment. This included all subjects whose IMP infusion started prior to the end of surgery, irrespective of the amount of IMP infused. Subjects were analyzed as randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BT524 | Amount of Red Blood Cells (RBCs) | 543.4 mL |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Amount of Red Blood Cells (RBCs) | 558.9 mL |
p-value: <0.83195% CI: [-157.83, 126.88]ANOVA
Secondary
Change in Viral Status
Number of subjects with change in status of viral infections
Time frame: Screening visit (up to 42 days prior to surgery) and closing visit (up to 181 days after surgery)
Population: Safety Analysis Set (SAF): All subjects who have received at least one dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BT524 | Change in Viral Status | 0 Participants |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Change in Viral Status | 0 Participants |
Secondary
Hospital Length of Stay After Surgery
Length of stay after surgery (days) = 'date of hospital discharge' minus 'date of surgery'. Where date of discharge is the date of discharge following the IMP treated surgery.
Time frame: From day of surgery until day of hospital discharge, an average of 16 days (up to 56 days)
Population: Modified Full Analysis Set (mFAS): All randomized subjects who received at least one dose of IMP prior to the 'end of surgery' and have at least one postdose efficacy assessment. This included all subjects whose IMP infusion started prior to the end of surgery, irrespective of the amount of IMP infused. Subjects were analyzed as randomized.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BT524 | Hospital Length of Stay After Surgery | >36 days | 7 Participants |
| BT524 | Hospital Length of Stay After Surgery | 29-36 days | 4 Participants |
| BT524 | Hospital Length of Stay After Surgery | 22-28 days | 13 Participants |
| BT524 | Hospital Length of Stay After Surgery | 15-21 days | 34 Participants |
| BT524 | Hospital Length of Stay After Surgery | 8-14 days | 39 Participants |
| BT524 | Hospital Length of Stay After Surgery | 1-7 days | 10 Participants |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Hospital Length of Stay After Surgery | 8-14 days | 49 Participants |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Hospital Length of Stay After Surgery | >36 days | 4 Participants |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Hospital Length of Stay After Surgery | 15-21 days | 17 Participants |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Hospital Length of Stay After Surgery | 29-36 days | 10 Participants |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Hospital Length of Stay After Surgery | 1-7 days | 12 Participants |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Hospital Length of Stay After Surgery | 22-28 days | 12 Participants |
Secondary
In-hospital Mortality
Number and percentages of subjects who died during hospital stay
Time frame: From day of surgery until day of hospital discharge, an average of 16 days (up to 56 days)
Population: Modified Full Analysis Set (mFAS): All randomized subjects who received at least one dose of IMP prior to the 'end of surgery' and have at least one postdose efficacy assessment. This included all subjects whose IMP infusion started prior to the end of surgery, irrespective of the amount of IMP infused. Subjects were analyzed as randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BT524 | In-hospital Mortality | 0 Participants |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | In-hospital Mortality | 0 Participants |
Secondary
Number of Subjects With Thrombosis or Thromboembolic Events (TEEs)
Total number of subjects with thrombosis or TEEs documented as treatment-emergent adverse events of special interest
Time frame: From day of surgery until closing visit (up to 181 days)
Population: Safety Analysis Set (SAF): All subjects who have received at least one dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BT524 | Number of Subjects With Thrombosis or Thromboembolic Events (TEEs) | 8 Participants |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Number of Subjects With Thrombosis or Thromboembolic Events (TEEs) | 13 Participants |
Secondary
Post-operative Blood Loss
Post-operative drainage volume in the first 24 hours after end of surgery
Time frame: From end of surgery (time of last suture) up to 24 hours after the end of surgery
Population: Modified Full Analysis Set (mFAS): All randomized subjects who received at least one dose of IMP prior to the 'end of surgery' and have at least one postdose efficacy assessment. This included all subjects whose IMP infusion started prior to the end of surgery, irrespective of the amount of IMP infused. Subjects were analyzed as randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BT524 | Post-operative Blood Loss | 306.3 mL |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Post-operative Blood Loss | 293.9 mL |
p-value: =0.80995% CI: [-88.84, 113.66]ANOVA
Secondary
Proportion (%) of Subjects With Successful Correction of Fibrinogen Level (FIBTEM A10) 15 Minutes After Start of First IMP Administration
Successful correction of the fibrinogen level is defined as restoring fibrinogen FIBTEM A10 baseline (prior surgery) levels measured by ROTEM (thromboelastometry) 15 minutes after start of first IMP administration
Time frame: Prior first dose, 15 minutes after start of first IMP administration
Population: Modified Full Analysis Set (mFAS): All randomized subjects who received at least one dose of IMP prior to the 'end of surgery' and have at least one postdose efficacy assessment. This included all subjects whose IMP infusion started prior to the end of surgery, irrespective of the amount of IMP infused. Subjects were analyzed as randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BT524 | Proportion (%) of Subjects With Successful Correction of Fibrinogen Level (FIBTEM A10) 15 Minutes After Start of First IMP Administration | 59 Participants |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Proportion (%) of Subjects With Successful Correction of Fibrinogen Level (FIBTEM A10) 15 Minutes After Start of First IMP Administration | 19 Participants |
p-value: <0.00195% CI: [26, 50.3]Cochran-Mantel-Haenszel
Secondary
Subjects With Rebleeds
Proportion (%) of subjects with rebleeds after the end of surgery until day 8
Time frame: End of surgery up to 8 days after surgery
Population: Modified Full Analysis Set (mFAS): All randomized subjects who received at least one dose of IMP prior to the 'end of surgery' and have at least one postdose efficacy assessment. This included all subjects whose IMP infusion started prior to the end of surgery, irrespective of the amount of IMP infused. Subjects were analyzed as randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BT524 | Subjects With Rebleeds | 0 Participants |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Subjects With Rebleeds | 5 Participants |
p-value: =0.02295% CI: [-8.9, -0.7]Cochran-Mantel-Haenszel
Secondary
Time to First Successful Correction of Fibrinogen Level
Correction of the fibrinogen level, measured via thromboelastometry (ROTEM/FIBTEM A10), within 15 minutes after IMP start, between 15 and 90 minutes after IMP start, after 90 minutes after IMP start, or unsuccessful correction. The 4 categories were compared between the two treatment arms using a Chi-square test.
Time frame: prior 1st dose, pre-dose, 15 minutes and 90 minutes after start of first IMP administration, end of surgery
Population: Modified Full Analysis Set (mFAS): All randomized subjects who received at least one dose of IMP prior to the 'end of surgery' and have at least one postdose efficacy assessment. This included all subjects whose IMP infusion started prior to the end of surgery, irrespective of the amount of IMP infused. Subjects were analyzed as randomized.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BT524 | Time to First Successful Correction of Fibrinogen Level | <=15 minutes after IMP start | 59 Participants |
| BT524 | Time to First Successful Correction of Fibrinogen Level | >15 and <= 90 minutes after IMP start | 17 Participants |
| BT524 | Time to First Successful Correction of Fibrinogen Level | >90 minutes after IMP start | 11 Participants |
| BT524 | Time to First Successful Correction of Fibrinogen Level | Unsuccessful correction | 20 Participants |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Time to First Successful Correction of Fibrinogen Level | Unsuccessful correction | 58 Participants |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Time to First Successful Correction of Fibrinogen Level | <=15 minutes after IMP start | 19 Participants |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Time to First Successful Correction of Fibrinogen Level | >90 minutes after IMP start | 16 Participants |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Time to First Successful Correction of Fibrinogen Level | >15 and <= 90 minutes after IMP start | 11 Participants |
p-value: <0.001Chi-squared
Secondary
Transfusion Requirements: Allogeneic Platelets
Total amount of transfusion products (allogeneic blood products) or autologous blood transfusion infused after start of first IMP administration until end of surgery. The end of surgery is defined as time of last suture.
Time frame: After start of first IMP administration until end of surgery, an average of 5 hours
Population: Modified Full Analysis Set (mFAS): All randomized subjects who received at least one dose of IMP prior to the 'end of surgery' and have at least one postdose efficacy assessment. This included all subjects whose IMP infusion started prior to the end of surgery, irrespective of the amount of IMP infused. Subjects were analyzed as randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BT524 | Transfusion Requirements: Allogeneic Platelets | 3.0 mL | Standard Deviation 30.94 |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Transfusion Requirements: Allogeneic Platelets | 3.6 mL | Standard Deviation 36.38 |
Secondary
Transfusion Requirements: Allogeneic Red Blood Cells
Total amount of transfusion products (allogeneic blood products) or autologous blood transfusion infused after start of first IMP administration until end of surgery. The end of surgery is defined as time of last suture.
Time frame: After start of first IMP administration until end of surgery, an average of 5 hours
Population: Modified Full Analysis Set (mFAS): All randomized subjects who received at least one dose of IMP prior to the 'end of surgery' and have at least one postdose efficacy assessment. This included all subjects whose IMP infusion started prior to the end of surgery, irrespective of the amount of IMP infused. Subjects were analyzed as randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BT524 | Transfusion Requirements: Allogeneic Red Blood Cells | 455.5 mL | Standard Deviation 492.19 |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Transfusion Requirements: Allogeneic Red Blood Cells | 488.4 mL | Standard Deviation 547.72 |
Secondary
Transfusion Requirements: Cell Salvage
Total amount of transfusion products (allogeneic blood products) or autologous blood transfusion infused after start of first IMP administration until end of surgery. The end of surgery is defined as time of last suture.
Time frame: After start of first IMP administration until end of surgery, an average of 5 hours
Population: Modified Full Analysis Set (mFAS): All randomized subjects who received at least one dose of IMP prior to the 'end of surgery' and have at least one postdose efficacy assessment. This included all subjects whose IMP infusion started prior to the end of surgery, irrespective of the amount of IMP infused. Subjects were analyzed as randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BT524 | Transfusion Requirements: Cell Salvage | 95.6 mL | Standard Deviation 244.57 |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Transfusion Requirements: Cell Salvage | 78.0 mL | Standard Deviation 234.77 |
Secondary
Transfusion Requirements, Cryoprecipitate
Total amount of transfusion products (allogeneic blood products) or autologous blood transfusion infused after start of first IMP administration until end of surgery. The end of surgery is defined as time of last suture.
Time frame: After start of first IMP administration until end of surgery, an average of 5 hours
Population: Modified Full Analysis Set (mFAS): All randomized subjects who received at least one dose of IMP prior to the 'end of surgery' and have at least one postdose efficacy assessment. This included all subjects whose IMP infusion started prior to the end of surgery, irrespective of the amount of IMP infused. Subjects were analyzed as randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BT524 | Transfusion Requirements, Cryoprecipitate | 0 mL | Standard Deviation 0 |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Transfusion Requirements, Cryoprecipitate | 0 mL | Standard Deviation 0 |
Secondary
Transfusion Requirements: Fresh Frozen Plasma
Total amount of transfusion products (allogeneic blood products) or autologous blood transfusion infused after start of first IMP administration until end of surgery. The end of surgery is defined as time of last suture.
Time frame: After start of first IMP administration until end of surgery, an average of 5 hours
Population: Modified Full Analysis Set (mFAS): All randomized subjects who received at least one dose of IMP prior to the 'end of surgery' and have at least one postdose efficacy assessment. This included all subjects whose IMP infusion started prior to the end of surgery, irrespective of the amount of IMP infused. Subjects were analyzed as randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BT524 | Transfusion Requirements: Fresh Frozen Plasma | 60.5 mL | Standard Deviation 217.68 |
| Fresh Frozen Plasma (FFP)/Cryoprecipitate (Cryo) | Transfusion Requirements: Fresh Frozen Plasma | 14.8 mL | Standard Deviation 110.94 |