Cardiac Complication During Procedure
Conditions
Keywords
Fibrinogen, cardiac surgery, high risk, cardiopulmonary bypass, bleeding, blood transfusion
Brief summary
The aim of the study is to show that first line treatment with concentrated fibrinogen has superiority over the conventional therapy with fresh frozen plasma (FFP), platelets, and cryoprecipitate in perioperative management of bleeding after complex cardiac surgery.
Detailed description
All patients will be recruited from the Queen Elizabeth II (QEII) Health Sciences Center, Halifax, Nova Scotia, which is the sole tertiary cardiac surgical referral center in Nova Scotia that performs approximately 1000 open heart surgical procedures yearly, including more than 700 isolated coronary artery bypass graft (CABG) procedures. Inclusion criteria: All patients who are scheduled for elective complex cardiac surgical procedures including, double procedures (aortic valve replacement+coronary artery bypass graft , mitral valve replacement+coronary artery bypass graft , aortic valve replacement+mitral valve replacement), redo-sternotomies, and aortic root repair +/-aortic valve replacement. Exclusion criteria: Any known congenital or preexisting bleeding disorder, preexisting clinically significant abnormal fibrinogen level, severe liver disease (alanine aminotransferase or aspartate aminotransferase \> 150 U/l), inability of providing informed consent, emergency surgery, pregnancy or nursing, age under 18 years, intake of anti-platelet drugs within the last 2- 5 days before surgery (low dose aspirin is allowed) allergy to concentrated fibrinogen or other components in the product, anemia (Hb \< 110), diagnosed deep venous thrombosis, pulmonary embolism, acute stroke or acute myocardial infarction. The primary outcome: Cumulative perioperative amount (number of units and total volume) of blood components used between the start of surgery and 24 hours after administration of the study drug or placebo. 'Blood Components' are defined as all fresh components of blood (RBCs, plasma, platelets, and Cryo). The secondary outcomes: Fibrinogen levels, hematocrit, prothrombin time (PT), partial prothrombin time (PTT), INR, platelet count, Hemoglobin (Hb), Thromboelastometry (ROTEM®, clotting time (CT), clot formation time (CFT), Angle, maximum clot firmness (MCF), Cardiovascular intensive care unit (CVICU-stay), Hospital-stay, In-Hospital Mortality, Hemoglobin, adverse events (anaphylaxis, stroke, myocardial infarction, pulmonary embolism, and deep vein thromboembolism) and usage of factor VII concentrate and human prothrombin complex (factors II, VII,IX, X), total avoidance of transfusion after cardiopulmonary bypass (CPB) 24h after administration of study drug or placebo.
Interventions
DRUGFibrinogen
Intravenous concentrated fibrinogen will be infused according to a hemostatic algorithm based on ROTEM (FIBTEM)
Sponsors
Nova Scotia Health Authority
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All patients who are scheduled for elective complex cardiac surgical procedures including * double procedures (aortic valve replacement (AVR)+CABG, mitral valve repair/replacement (MVR)+CABG, AVR+MVR) * Redo-sternotomies * Aortic root repair +/- AVR
Exclusion criteria
* Any known congenital or pre-existing bleeding disorder * pre-existing clinically significant abnormal fibrinogen level (normal: 2.5-4.79g/l) * severe liver disease (alanine aminotransferase or aspartate aminotransferase \> 150 U/l) * inability to provide informed consent * emergency surgery * pregnancy or nursing * age under 18 years * intake of anti-platelet drugs within2- 5 days preoperatively (low dose ASA is allowed) * allergy to concentrated fibrinogen or other components in the product * anemia (Hgb \< 110) * diagnosed deep vein thrombosis (DVT) * pulmonary embolism * acute stroke * acute myocardial infarction
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Transfusion Units | 24 hours after administration of study drug | Including packed red cells, frozen plasma, platelets, cryoprecipitates |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fibrinogen Plasma Concentration (g/L) | 24h after infusion of study drug | — |
| Hematocrit (%) | 24h after infusion of study drug | — |
| Hemoglobin Concentration (g/L) | 24h after infusion of study drug | — |
| Platelet Count (10^3/μL) | 24h after infusion of study drug | — |
| Partial Thromboplastin Time (s) | 24h after infusion of study drug | — |
| International Normalized Ratio | 24h after infusion of study drug | International normalized ratio (INR) is calculated based on the prothrombin time (PT) test results.The PT is usually measured in seconds and is compared to a normal range that reflects PT values in healthy individuals. Because the reagents used to perform the PT test vary from one laboratory to another and even within the same laboratory over time, the normal ranges also will fluctuate. To standardize results across different laboratories in the world, a World Health Organization (WHO) committee developed and recommended the use of the Internationalized Normalized Ratio (INR). The INR is calculated with the ratio of the patient's prothrombin time (PT test) to a normal prothrombin time (control) sample (PT normal): INR=PT test:PT normal. The normal range is from 0.9 to 1.2. The higher the value the more is the patient anticoagulated. This means the patient's blood is thinner with a lower concentration of coagulation factors. |
| Prothrombin Time (s) | 24h after infusion of study drug | The prothrombin time (PT) test evaluates how well all of the coagulation factors in the extrinsic and common pathways of the coagulation cascade work together. Included are: factors I (Fibrinogen), II (Prothrombin), V, VII and X. |
| EXTEM Clotting Time (s) | 24h after infusion of study drug | EXTEM = rotational thrombelastometry (measurement of extrinsic coagulation pathway); clotting time: time from start of the measurement until initiation of clotting (thrombin formation, start of clot polymerisation). |
| INTEM Clotting Time (s) | 24h after infusion of study drug | INTEM = rotational thrombelastometry (measurement of intrinsic coagulation pathway); clotting time: time from start of the measurement until initiation of clotting (thrombin formation, start of clot polymerisation). |
| INTEM Maximum Clot Firmness (mm) | 24h after infusion of study drug | INTEM = rotational thrombelastometry (measurement of intrinsic coagulation pathway); maximum clot firmness: increasing stabilisation of the clot by the polymerised fibrin, platelets as well as factor XIII. |
| FIBTEM Clotting Time (s) | 24h after infusion of study drug | FIBTEM = rotational thrombelastometry (measurement of functional fibrinogen); clotting time: time from start of the measurement until initiation of clotting (thrombin formation, start of clot polymerisation). |
| FIBTEM MCF (Maximum Clot Firmness) | 24 hours after study drug administration | Rotational thrombelastometry (measurement of functional fibrinogen). Rotational thrombelastometry (ROTEM) is a point-of-care viscoelastic coagulation test. The device provides four channels for simultaneous assays. With the so called FIBTEM assay coagulation is activated by a small amount of tissue thromboplastin (tissue factor) and platelets are blocked with cytochalasin D. The resulting clot is therefore only depending on fibrin formation and fibrin polymerisation. The maximum clot firmness (MCF) is the amplitude in mm on the result graph representing the increasing stabilisation of the clot. |
| HEPTEM Clotting Time (s) | 24h after infusion of study drug | HEPTEM = rotational thrombelastometry (measurement of INTEM with heparinase);clotting time: time from start of the measurement until initiation of clotting (thrombin formation, start of clot polymerisation). |
| HEPTEM Maximum Clot Firmness (mm) | 24h after infusion of study drug | HEPTEM = rotational thrombelastometry (measurement of INTEM with heparinase); maximum clot firmness: increasing stabilisation of the clot by the polymerised fibrin, platelets as well as factor XIII. |
| Total Avoidance of Transfusions | 24h after infusion of study drug | Total avoidance of any transfusion after cardiopulmonary bypass (CPB) 24h after administration of study drug or placebo. |
| EXTEM Maximum Clot Firmness (mm) | 24h after infusion of study drug | EXTEM = rotational thrombelastometry (measurement of extrinsic coagulation pathway); maximum clot firmness: increasing stabilisation of the clot by the polymerised fibrin, platelets as well as factor XIII. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Overall Numbers of Patients Receiving Blood Products | 24 hours after administration of study drug | Including Packed Red Cells, Fresh Frozen Plasma, Platelets, Cryoprecipitate and coagulation factor concentrates. The study was not sufficiently powered to test differences between this outcome. |
Countries
Canada
Participant flow
Recruitment details
The investigation included 62 patients (\>18 years old) for elective, high-risk cardiac surgery (double procedures (aortic valve replacement (AVR)+coronary artery bypass grafting (CABG), mitral valve repair/replacement (MVR)+CABG, AVR+MVR), redo-sternotomies, and aortic root repair±AVR) with a pre-operative fibrinogen level of ≤3.8 g/L.
Participants by arm
| Arm | Count |
|---|---|
| RiaSTAP Intravenous fibrinogen(RiaSTAP) will be administered according to FIBTEM based calculation formula
Fibrinogen: Intravenous concentrated fibrinogen will be infused according to a hemostatic algorithm based on ROTEM (FIBTEM) | 28 |
| Intravenous Saline Intravenous saline (placebo) will be calculated according to FIBTEM based calculation formula
Placebo: Intravenous saline will be infused with the same volume of the study drug. | 30 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Missing data at primary outcome time poi | 1 | 1 |
| Overall Study | Protocol Violation | 2 | 1 |
Baseline characteristics
| Characteristic | RiaSTAP | Intravenous Saline | Total |
|---|---|---|---|
| Age, Continuous | 59 years STANDARD_DEVIATION 18 | 65 years STANDARD_DEVIATION 11 | 62 years STANDARD_DEVIATION 14 |
| Body Mass Index | 28.8 kg/m^2 STANDARD_DEVIATION 4.14 | 29 kg/m^2 STANDARD_DEVIATION 4.03 | 28.9 kg/m^2 STANDARD_DEVIATION 4 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Canada | 28 participants | 30 participants | 58 participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 23 Participants | 27 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 27 | 0 / 29 |
| other Total, other adverse events | 1 / 27 | 2 / 29 |
| serious Total, serious adverse events | 5 / 27 | 9 / 29 |
Outcome results
Primary
Cumulative Transfusion Units
Including packed red cells, frozen plasma, platelets, cryoprecipitates
Time frame: 24 hours after administration of study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RiaSTAP | Cumulative Transfusion Units | 0 Transfusion Units |
| Intravenous Saline | Cumulative Transfusion Units | 0 Transfusion Units |
Comparison: Normality among study outcomes was investigated with Shapiro-Wilk tests, histograms, boxplots, and graphing of residuals, revealing that the data were not normally distributed, and primary outcomes were zero inflated. Therefore, we used non-parametric Mann-Whitney U-tests with a 2-sided type I error rate of 5%. We tested the null hypothesis of no difference in primary and secondary outcomes between groups 24 hours after infusion of the study drug.p-value: 0.908Wilcoxon (Mann-Whitney)
Secondary
EXTEM Clotting Time (s)
EXTEM = rotational thrombelastometry (measurement of extrinsic coagulation pathway); clotting time: time from start of the measurement until initiation of clotting (thrombin formation, start of clot polymerisation).
Time frame: 24h after infusion of study drug
Population: One patient in the fibrinogen group (RiaStap) had missing data at 24h after infusion of study drug. One patient in the placebo group had missing data at 24h after infusion of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RiaSTAP | EXTEM Clotting Time (s) | 68 seconds |
| Intravenous Saline | EXTEM Clotting Time (s) | 68 seconds |
Comparison: Normality among study outcomes was investigated with Shapiro-Wilk tests, histograms, boxplots, and graphing of residuals, revealing that this variable was not normally distributed. Therefore, we used non-parametric Mann-Whitney U-tests with a 2-sided type I error rate of 5%. We tested the null hypothesis of no difference in secondary outcomes between groups 24 hours after infusion of the study drug.p-value: 0.941Wilcoxon (Mann-Whitney)
Secondary
EXTEM Maximum Clot Firmness (mm)
EXTEM = rotational thrombelastometry (measurement of extrinsic coagulation pathway); maximum clot firmness: increasing stabilisation of the clot by the polymerised fibrin, platelets as well as factor XIII.
Time frame: 24h after infusion of study drug
Population: One patient in the fibrinogen group (RiaStap) had missing data at 24h after infusion of study drug. One patient in the placebo group had missing data at 24h after infusion of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RiaSTAP | EXTEM Maximum Clot Firmness (mm) | 66 mm |
| Intravenous Saline | EXTEM Maximum Clot Firmness (mm) | 64 mm |
Comparison: Normality among study outcomes was investigated with Shapiro-Wilk tests, histograms, boxplots, and graphing of residuals, revealing that this variable was not normally distributed. Therefore, we used non-parametric Mann-Whitney U-tests with a 2-sided type I error rate of 5%. We tested the null hypothesis of no difference in secondary outcomes between groups 24 hours after infusion of the study drug.p-value: 0.09Wilcoxon (Mann-Whitney)
Secondary
Fibrinogen Plasma Concentration (g/L)
Time frame: 24h after infusion of study drug
Population: Six patients had missing data in the fibrinogen group (RiaStap) at 24h after infusion of study drug. Six patients had missing data in the placebo group at 24h after infusion of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RiaSTAP | Fibrinogen Plasma Concentration (g/L) | 4.65 g/L | Standard Deviation 0.94 |
| Intravenous Saline | Fibrinogen Plasma Concentration (g/L) | 4.15 g/L | Standard Deviation 0.68 |
Comparison: We tested the null hypothesis of no difference in primary and secondary outcomes between groups 24 hours after infusion of the study drug. Normality among study outcomes was investigated with Shapiro-Wilk tests, histograms, boxplots, and graphing of residuals. For normally distributed data unequal variance t tests were used.p-value: 0.047t-test, 2 sided
Secondary
FIBTEM Clotting Time (s)
FIBTEM = rotational thrombelastometry (measurement of functional fibrinogen); clotting time: time from start of the measurement until initiation of clotting (thrombin formation, start of clot polymerisation).
Time frame: 24h after infusion of study drug
Population: One patient in the fibrinogen group (RiaStap) had missing data at 24h after infusion of study drug. One patient in the placebo group had missing data at 24h after infusion of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RiaSTAP | FIBTEM Clotting Time (s) | 64 seconds |
| Intravenous Saline | FIBTEM Clotting Time (s) | 59 seconds |
Comparison: Normality among study outcomes was investigated with Shapiro-Wilk tests, histograms, boxplots, and graphing of residuals, revealing that this variable was not normally distributed. Therefore, we used non-parametric Mann-Whitney U-tests with a 2-sided type I error rate of 5%. We tested the null hypothesis of no difference in secondary outcomes between groups 24 hours after infusion of the study drug.p-value: 0.549Wilcoxon (Mann-Whitney)
Secondary
FIBTEM MCF (Maximum Clot Firmness)
Rotational thrombelastometry (measurement of functional fibrinogen). Rotational thrombelastometry (ROTEM) is a point-of-care viscoelastic coagulation test. The device provides four channels for simultaneous assays. With the so called FIBTEM assay coagulation is activated by a small amount of tissue thromboplastin (tissue factor) and platelets are blocked with cytochalasin D. The resulting clot is therefore only depending on fibrin formation and fibrin polymerisation. The maximum clot firmness (MCF) is the amplitude in mm on the result graph representing the increasing stabilisation of the clot.
Time frame: 24 hours after study drug administration
Population: One patient in the fibrinogen group (RiaStap) had missing data at 24h after infusion of study drug. One patient in the placebo group had missing data at 24h after infusion of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RiaSTAP | FIBTEM MCF (Maximum Clot Firmness) | 27 mm |
| Intravenous Saline | FIBTEM MCF (Maximum Clot Firmness) | 23 mm |
Comparison: Normality among study outcomes was investigated with Shapiro-Wilk tests, histograms, boxplots, and graphing of residuals, revealing that the FIBTEM MCF data was not normally distributed. Therefore, we used non-parametric Mann-Whitney U-tests with a 2-sided type I error rate of 5%. We tested the null hypothesis of no difference in secondary outcomes between groups 24 hours after infusion of the study drug.p-value: 0.022Wilcoxon (Mann-Whitney)
Secondary
Hematocrit (%)
Time frame: 24h after infusion of study drug
Population: Four patients in the fibrinogen group (RiaStap) had missing data at 24h after infusion of study drug. Two patients in the placebo group had missing data at 24h after infusion of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RiaSTAP | Hematocrit (%) | 0.29 Hematocrit percent | Standard Deviation 0.04 |
| Intravenous Saline | Hematocrit (%) | 0.28 Hematocrit percent | Standard Deviation 0.05 |
Comparison: We tested the null hypothesis of no difference in primary and secondary outcomes between groups 24 hours after infusion of the study drug. Normality among study outcomes was investigated with Shapiro-Wilk tests, histograms, boxplots, and graphing of residuals. For normally distributed data unequal variance t tests were used.p-value: 0.729t-test, 2 sided
Secondary
Hemoglobin Concentration (g/L)
Time frame: 24h after infusion of study drug
Population: Four patients in the fibrinogen group (RiaStap) had missing data at 24h after infusion of study drug. Two patients in the placebo group had missing data at 24h after infusion of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RiaSTAP | Hemoglobin Concentration (g/L) | 95 g/L | Standard Deviation 11.9 |
| Intravenous Saline | Hemoglobin Concentration (g/L) | 95 g/L | Standard Deviation 14.8 |
Comparison: We tested the null hypothesis of no difference in primary and secondary outcomes between groups 24 hours after infusion of the study drug. Normality among study outcomes was investigated with Shapiro-Wilk tests, histograms, boxplots, and graphing of residuals. For normally distributed data unequal variance t tests were used.p-value: 0.93t-test, 2 sided
Secondary
HEPTEM Clotting Time (s)
HEPTEM = rotational thrombelastometry (measurement of INTEM with heparinase);clotting time: time from start of the measurement until initiation of clotting (thrombin formation, start of clot polymerisation).
Time frame: 24h after infusion of study drug
Population: One patient in the fibrinogen group (RiaStap) had missing data at 24h after infusion of study drug. One patient in the placebo group had missing data at 24h after infusion of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RiaSTAP | HEPTEM Clotting Time (s) | 162 seconds |
| Intravenous Saline | HEPTEM Clotting Time (s) | 162 seconds |
Comparison: Normality among study outcomes was investigated with Shapiro-Wilk tests, histograms, boxplots, and graphing of residuals, revealing that this variable was not normally distributed. Therefore, we used non-parametric Mann-Whitney U-tests with a 2-sided type I error rate of 5%. We tested the null hypothesis of no difference in secondary outcomes between groups 24 hours after infusion of the study drug.p-value: 0.455Wilcoxon (Mann-Whitney)
Secondary
HEPTEM Maximum Clot Firmness (mm)
HEPTEM = rotational thrombelastometry (measurement of INTEM with heparinase); maximum clot firmness: increasing stabilisation of the clot by the polymerised fibrin, platelets as well as factor XIII.
Time frame: 24h after infusion of study drug
Population: One patient in the fibrinogen group (RiaStap) had missing data at 24h after infusion of study drug. One patient in the placebo group had missing data at 24h after infusion of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RiaSTAP | HEPTEM Maximum Clot Firmness (mm) | 62 mm |
| Intravenous Saline | HEPTEM Maximum Clot Firmness (mm) | 61 mm |
Comparison: Normality among study outcomes was investigated with Shapiro-Wilk tests, histograms, boxplots, and graphing of residuals, revealing that this variable was not normally distributed. Therefore, we used non-parametric Mann-Whitney U-tests with a 2-sided type I error rate of 5%. We tested the null hypothesis of no difference in secondary outcomes between groups 24 hours after infusion of the study drug.p-value: 0.5Wilcoxon (Mann-Whitney)
Secondary
INTEM Clotting Time (s)
INTEM = rotational thrombelastometry (measurement of intrinsic coagulation pathway); clotting time: time from start of the measurement until initiation of clotting (thrombin formation, start of clot polymerisation).
Time frame: 24h after infusion of study drug
Population: One patient in the fibrinogen group (RiaStap) had missing data at 24h after infusion of study drug. One patient in the placebo group had missing data at 24h after infusion of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RiaSTAP | INTEM Clotting Time (s) | 161 seconds |
| Intravenous Saline | INTEM Clotting Time (s) | 164 seconds |
Comparison: Normality among study outcomes was investigated with Shapiro-Wilk tests, histograms, boxplots, and graphing of residuals, revealing that this variable was not normally distributed. Therefore, we used non-parametric Mann-Whitney U-tests with a 2-sided type I error rate of 5%. We tested the null hypothesis of no difference in secondary outcomes between groups 24 hours after infusion of the study drug.p-value: 0.658Wilcoxon (Mann-Whitney)
Secondary
INTEM Maximum Clot Firmness (mm)
INTEM = rotational thrombelastometry (measurement of intrinsic coagulation pathway); maximum clot firmness: increasing stabilisation of the clot by the polymerised fibrin, platelets as well as factor XIII.
Time frame: 24h after infusion of study drug
Population: One patient in the fibrinogen group (RiaStap) had missing data at 24h after infusion of study drug. One patient in the placebo group had missing data at 24h after infusion of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RiaSTAP | INTEM Maximum Clot Firmness (mm) | 64 mm |
| Intravenous Saline | INTEM Maximum Clot Firmness (mm) | 63 mm |
Comparison: Normality among study outcomes was investigated with Shapiro-Wilk tests, histograms, boxplots, and graphing of residuals, revealing that this variable was not normally distributed. Therefore, we used non-parametric Mann-Whitney U-tests with a 2-sided type I error rate of 5%. We tested the null hypothesis of no difference in secondary outcomes between groups 24 hours after infusion of the study drug.p-value: 0.182Wilcoxon (Mann-Whitney)
Secondary
International Normalized Ratio
International normalized ratio (INR) is calculated based on the prothrombin time (PT) test results.The PT is usually measured in seconds and is compared to a normal range that reflects PT values in healthy individuals. Because the reagents used to perform the PT test vary from one laboratory to another and even within the same laboratory over time, the normal ranges also will fluctuate. To standardize results across different laboratories in the world, a World Health Organization (WHO) committee developed and recommended the use of the Internationalized Normalized Ratio (INR). The INR is calculated with the ratio of the patient's prothrombin time (PT test) to a normal prothrombin time (control) sample (PT normal): INR=PT test:PT normal. The normal range is from 0.9 to 1.2. The higher the value the more is the patient anticoagulated. This means the patient's blood is thinner with a lower concentration of coagulation factors.
Time frame: 24h after infusion of study drug
Population: Four patients in the fibrinogen group (RiaStap) had missing data at 24h after infusion of study drug. Three patients in the placebo group had missing data at 24h after infusion of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RiaSTAP | International Normalized Ratio | 1.2 Ratio |
| Intravenous Saline | International Normalized Ratio | 1.2 Ratio |
Comparison: Normality among study outcomes was investigated with Shapiro-Wilk tests, histograms, boxplots, and graphing of residuals, revealing that this variable was not normally distributed. Therefore, we used non-parametric Mann-Whitney U-tests with a 2-sided type I error rate of 5%. We tested the null hypothesis of no difference in secondary outcomes between groups 24 hours after infusion of the study drug.p-value: 0.794Wilcoxon (Mann-Whitney)
Secondary
Partial Thromboplastin Time (s)
Time frame: 24h after infusion of study drug
Population: Four patients in the fibrinogen group (RiaStap) had missing data at 24h after infusion of study drug. Two patients in the placebo group had missing data at 24h after infusion of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RiaSTAP | Partial Thromboplastin Time (s) | 31 seconds |
| Intravenous Saline | Partial Thromboplastin Time (s) | 28.5 seconds |
Comparison: Normality among study outcomes was investigated with Shapiro-Wilk tests, histograms, boxplots, and graphing of residuals, revealing that this variable was not normally distributed. Therefore, we used non-parametric Mann-Whitney U-tests with a 2-sided type I error rate of 5%. We tested the null hypothesis of no difference in secondary outcomes between groups 24 hours after infusion of the study drug.p-value: 0.035Wilcoxon (Mann-Whitney)
Secondary
Platelet Count (10^3/μL)
Time frame: 24h after infusion of study drug
Population: Four patients in the fibrinogen group (RiaStap) had missing data at 24h after infusion of study drug. Two patients in the placebo group had missing data at 24h after infusion of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RiaSTAP | Platelet Count (10^3/μL) | 129 cells*10^3/μL | Standard Deviation 31.4 |
| Intravenous Saline | Platelet Count (10^3/μL) | 117 cells*10^3/μL | Standard Deviation 29.3 |
p-value: 0.169t-test, 2 sided
Secondary
Prothrombin Time (s)
The prothrombin time (PT) test evaluates how well all of the coagulation factors in the extrinsic and common pathways of the coagulation cascade work together. Included are: factors I (Fibrinogen), II (Prothrombin), V, VII and X.
Time frame: 24h after infusion of study drug
Population: Four patients in the fibrinogen group (RiaStap) had missing data at 24h after infusion of study drug. Three patients in the placebo group had missing data at 24h after infusion of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RiaSTAP | Prothrombin Time (s) | 13.9 seconds |
| Intravenous Saline | Prothrombin Time (s) | 13.8 seconds |
Comparison: Normality among study outcomes was investigated with Shapiro-Wilk tests, histograms, boxplots, and graphing of residuals, revealing that this variable was not normally distributed. Therefore, we used non-parametric Mann-Whitney U-tests with a 2-sided type I error rate of 5%. We tested the null hypothesis of no difference in secondary outcomes between groups 24 hours after infusion of the study drug.p-value: 0.828Wilcoxon (Mann-Whitney)
Secondary
Total Avoidance of Transfusions
Total avoidance of any transfusion after cardiopulmonary bypass (CPB) 24h after administration of study drug or placebo.
Time frame: 24h after infusion of study drug
Population: One patient in the fibrinogen group (RiaStap) had missing data at 24h after infusion of study drug. One patient in the placebo group had missing data at 24h after infusion of study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RiaSTAP | Total Avoidance of Transfusions | Avoided transfusions | 20 Participants |
| RiaSTAP | Total Avoidance of Transfusions | Had any transfusion | 7 Participants |
| Intravenous Saline | Total Avoidance of Transfusions | Avoided transfusions | 21 Participants |
| Intravenous Saline | Total Avoidance of Transfusions | Had any transfusion | 8 Participants |
p-value: 1Fisher Exact
Other Pre-specified
Overall Numbers of Patients Receiving Blood Products
Including Packed Red Cells, Fresh Frozen Plasma, Platelets, Cryoprecipitate and coagulation factor concentrates. The study was not sufficiently powered to test differences between this outcome.
Time frame: 24 hours after administration of study drug
Population: The placebo group had one dropout during the study because of a study protocol violation and one patient with missing data at the primary outcome time point (29pt). The fibrinogen group hat three dropouts during the study because of two study protocol violation, one death and one patient with missing data at the primary outcome time point (27pt).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RiaSTAP | Overall Numbers of Patients Receiving Blood Products | 7 Participants |
| Intravenous Saline | Overall Numbers of Patients Receiving Blood Products | 8 Participants |