ATIII Deficiency
Conditions
Brief summary
The purpose of this study is to test whether the administration of ATIII during the intra-operative period results in improved anticoagulation for cardiopulmonary bypass (CPB) and an attenuation of the activation of the coagulation cascade, as represented by a decrease in fibrin degradation products. The investigators believe this benefit would extend into the post-operative period resulting in a decreased incidence of thrombosis generation, as represented by a decrease in fibrin degradation products in the ICU period.
Detailed description
If Preoperative ATIII functional assay level is less than 70% patients would be enrolled and randomized to either Placebo (normal saline) or ATIII.
Interventions
DRUGAnti-thrombin III
Intraoperatively- (correcting to 100%) according to the following formula: Units required = ((100%- baseline ATIII level\*%) X body weight)/1.4 * expressed as a % normal level based on functional ATIII assay
OTHERPlacebo
Normal saline placebo
Sponsors
Grifols Biologicals, LLC
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 7 Months
Healthy volunteers
No
Inclusion criteria
* All patients less than 7 months of age going for cardiac surgery that will require cardiopulmonary bypass (CPB) with a documented ATIII level below 70%
Exclusion criteria
* Less than 2.5kg * Known or suspected hereditary ATIII deficiency (family history of venous thrombosis with decreased plasma levels of ATIII and no other potential causes of acquired decreased ATIII) * On Ecmo (extracorporeal membrane oxygenation ) at time of surgery * Known history of thrombosis * Renal failure as described by the pediatric RIFLE criteria * H/o intracranial hemorrhage * Prematurity less than 37 weeks estimated gestational age * Previously diagnosed pro-thrombotic or hemorrhagic disorder * Prior ATIII supplementation * Prior therapeutic anticoagulant use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in the Mean and Standard Deviation (SD) of the Calibrated Automated Thrombography (CAT) Measurements of the Control and ATIII Groups at Time 5 (on Arrival in ICU) | Time 5 (on arrival in ICU) | Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the mean and Standard Deviation (SD) of the Calibrated Automated Thrombography (CAT) measurements of the control and ATIII groups at Time 5 (on arrival in ICU). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in the Mean and SD of the Calibrated Automated Thrombography (CAT) Measurements of the Control and ATIII Groups at Times 5-Time 7 (ICU Arrival to Post Operative Day 4) | ICU arrival (Time 5) to Time 7 (Post-operative Day 4) | Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the mean and SD of the Calibrated Automated Thrombography (CAT) measurements of the control and ATIII groups at times 5-Time 7 (ICU arrival to Post Operative Day 4) |
| Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7 | T1, T2, T3, T5, T6 and T7 | Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the mean of the ATIII (functional assay) of the control and ATIII groups at T1, T2, T3, T5, T6 and T7 (Baseline, 30 min after study drug, 30 min on CPB, Arrival in ICU, POD 2, and POD 4). Data reported as % Functional Activity, which is calculated as the ability of Antithrombin (AT) to suppress FIIa or FXa in the presence of heparin compared to normograms, and expressed as a percentage. |
| Difference in the Median of the ATIII (Functional Assay) of the Control and ATIII Groups at T4 | T4 (just prior to coming off of CPB) | Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the median of the ATIII (functional assay) of the control and ATIII groups at T4 (just prior to coming off of CPB). Data reported as % Functional Activity, which is calculated as the ability of Antithrombin (AT) to suppress FIIa or FXa in the presence of heparin compared to normograms, and expressed as a percentage. |
| Difference in the Median of the D Dimer of the Control and ATIII Groups at T1, T5, T6 and T7 | T1, T5, T6 and T7 | Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the median of the D dimer of the control and ATIII groups at T1 (Baseline), T5 (Arrival in Intensive Care Unit), T6 (Post-Operative Day 2) and T7 (Post-Operative Day 4). |
| Residual Heparin at the ICU Arrival Time Point Represented by a Decreased Anti Factor Xa Level. | T5 (Intensive Care Unit Arrival) | Evidence of a decreased amount of residual heparin at the Intensive Care Unit arrival time point (T5) represented by a decreased anti factor Xa level. |
| Evidence of Decreased Inflammation Represented by a Decrease in Inflammatory Markers in the ATIII Group | Baseline (T1) to Post-Operative Day 4 (T7) | Evidence of decreased inflammation represented by a decrease in inflammatory markers in the ATIII group. |
| Total Dose of Heparin While on Cardiopulmonary Bypass | T1 (Baseline) to T5 (Arrival in ICU) | Total dose of Heparin while on Cardiopulmonary Bypass |
| Protamine Dose Determined by Hemostasis Management System Machine (mg/kg) | T1 (Baseline) to T5 (Arrival in ICU) | Protamine dose determined by Hemostasis Management system machine (mg/kg) |
| Total Volume of Blood Products While on CPB | Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4) | Total volume of blood products exposed intraoperatively including the pump prime (ml/kg) |
| Time From Protamine Administration to Skin Dressing | Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4) | Time from protamine administration to skin dressing |
| Total Volume of Fresh Frozen Plasma Given Prior to CPB | Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4) | Total volume of Fresh Frozen Plasma given prior to CPB, including the pump prime (ml/kg) |
| Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively | Baseline (Intraoperatively) | Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively |
| Volume of Postoperative Blood Loss | From 10min post protamine administration to 24 hour post protamine administration | Volume of postoperative blood loss from 10min post protamine administration to 24 hour post protamine administration- (ml/kg) |
| Chest Tube Output (Protamine Time Plus 24 Hours) in Milliliters | protamine time plus 24 hours | Chest Tube output (protamine time plus 24 hours) in milliliters |
| Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group | 24 Hours Post-Operatively | Number of packed Fresh frozen plasma units, Platelet Units, cryo-precipitate units, and Red Blood Cell units transfused 24 hours post-operatively for each group (not total units transfused for each subject) |
| Number of Total Blood Product Units Transfused 24-hours Post-operatively by Group | 24 Hours Post-Operatively | Number of total blood product units (including packed Fresh frozen plasma units, Platelet Units, cryo-precipitate units, and Red Blood Cell units) transfused 24 hours post-operatively for each group (not total units transfused for each subject) |
| Total Dose of Recombinant Factor 7a (VIIa) Used Intraoperatively | Intraoperatively | Total Dose of rescue recombinant factor 7a (VIIa) used intraoperatively |
| Length of Post Operative Ventilation in Days | ICU arrival (Time 5) to Time 7 (Post-Operative Day 4) | Length of post operative ventilation in days |
| Incidence of Extracorporeal Membrane Oxygenation (ECMO) Support Within 24 Hours Postoperatively | Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) | Study the safety profile of dosing the ATIII by monitoring the incidence of extracorporeal membrane oxygenation (ECMO) support within 24 hours postoperatively. |
| Incidence of Mediastinal Exploration Within 24 Hours Postoperatively | Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) | Study the safety profile of dosing the ATIII by monitoring the incidence of mediastinal exploration within 24 hours postoperatively |
| Incidence (Number) of Thrombotic Events Documented | Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) | Study the safety profile of dosing the ATIII by monitoring the incidence (number) of thrombotic events documented. |
| Incidence of New Onset Renal Failure, Defined by Stage 3 of the AKIN Criteria | Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) | Study the safety profile of dosing the ATIII by monitoring the incidence of new onset renal failure, defined by stage 3 of the Acute Kidney Injury Network (AKIN) criteria. 1. Serum creatinine increase ≥26.5 μmol/l (≥0.3 mg/dl) or increase to 1.5-2.0-fold from baseline, urine output \<0.5 ml/kg/h for 6 hours 2. Serum creatinine increase \>2.0-3.0-fold from baseline, urine output \<0.5 ml/kg/h for 12 hours 3. Serum creatinine increase \>3.0-fold from baseline or serum creatinine ≥354 μmol/l (≥4.0 mg/dl) with an acute increase of at least 44 μmol/l (0.5 mg/dl) or need for Renal replacement therapy (RRT), urine output \<0.3 ml/kg/h for 24 h or anuria for 12 hours or need for RRT |
| Incidence (Number) of Newly Diagnosed Intracranial Hemorrhage | Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) | Study the safety profile of dosing the ATIII by monitoring the incidence (number) of newly diagnosed intracranial hemorrhage |
| Length of Time to Delayed Sternal Closure Measured in Days | Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4) | Study the safety profile of dosing the ATIII by monitoring the length of time to delayed sternal closure measured in days |
Countries
United States
Participant flow
Recruitment details
Five subjects enrolled but withdrew prior to randomization
Participants by arm
| Arm | Count |
|---|---|
| Anti-thrombin III Intraoperatively- (correcting to 100%) according to the following formula:
Units required = ((100%- baseline ATIII level\*%) X body weight)/1.4
\* expressed as a % normal level based on functional ATIII assay | 20 |
| Placebo Placebo: Normal saline placebo | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Anti-thrombin III | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 9.8 days STANDARD_DEVIATION 19.7 | 17.2 days STANDARD_DEVIATION 30.2 | 14.6 days STANDARD_DEVIATION 26.1 |
| Region of Enrollment United States | 20 participants | 20 participants | 40 participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Male | 14 Participants | 13 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 20 | 7 / 20 |
| serious Total, serious adverse events | 3 / 20 | 8 / 20 |
Outcome results
Primary
Difference in the Mean and Standard Deviation (SD) of the Calibrated Automated Thrombography (CAT) Measurements of the Control and ATIII Groups at Time 5 (on Arrival in ICU)
Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the mean and Standard Deviation (SD) of the Calibrated Automated Thrombography (CAT) measurements of the control and ATIII groups at Time 5 (on arrival in ICU).
Time frame: Time 5 (on arrival in ICU)
Population: The laboratory was unable to perform this blood assay due to technical issues and no results were generated.
Secondary
Chest Tube Output (Protamine Time Plus 24 Hours) in Milliliters
Chest Tube output (protamine time plus 24 hours) in milliliters
Time frame: protamine time plus 24 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anti-thrombin III | Chest Tube Output (Protamine Time Plus 24 Hours) in Milliliters | 59.0 milliters |
| Placebo | Chest Tube Output (Protamine Time Plus 24 Hours) in Milliliters | 113.0 milliters |
p-value: 0.016Wilcoxon (Mann-Whitney)
Secondary
Difference in the Mean and SD of the Calibrated Automated Thrombography (CAT) Measurements of the Control and ATIII Groups at Times 5-Time 7 (ICU Arrival to Post Operative Day 4)
Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the mean and SD of the Calibrated Automated Thrombography (CAT) measurements of the control and ATIII groups at times 5-Time 7 (ICU arrival to Post Operative Day 4)
Time frame: ICU arrival (Time 5) to Time 7 (Post-operative Day 4)
Population: The laboratory was unable to perform this blood assay due to technical difficulties and no results were generated.
Secondary
Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7
Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the mean of the ATIII (functional assay) of the control and ATIII groups at T1, T2, T3, T5, T6 and T7 (Baseline, 30 min after study drug, 30 min on CPB, Arrival in ICU, POD 2, and POD 4). Data reported as % Functional Activity, which is calculated as the ability of Antithrombin (AT) to suppress FIIa or FXa in the presence of heparin compared to normograms, and expressed as a percentage.
Time frame: T1, T2, T3, T5, T6 and T7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Anti-thrombin III | Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7 | T1 (Baseline) | 54 % Functional Activity | Standard Deviation 12 |
| Anti-thrombin III | Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7 | T2 (30 minutes post study drug) | 99 % Functional Activity | Standard Deviation 19 |
| Anti-thrombin III | Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7 | T3 (30 minutes on CPB) | 83 % Functional Activity | Standard Deviation 20 |
| Anti-thrombin III | Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7 | T5 (Arrival in ICU) | 82 % Functional Activity | Standard Deviation 18 |
| Anti-thrombin III | Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7 | T6 (POD 2) | 58 % Functional Activity | Standard Deviation 15 |
| Anti-thrombin III | Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7 | T7 (POD 4) | 70.7 % Functional Activity | Standard Deviation 20 |
| Placebo | Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7 | T6 (POD 2) | 57 % Functional Activity | Standard Deviation 14 |
| Placebo | Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7 | T1 (Baseline) | 54 % Functional Activity | Standard Deviation 13 |
| Placebo | Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7 | T5 (Arrival in ICU) | 63 % Functional Activity | Standard Deviation 19 |
| Placebo | Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7 | T2 (30 minutes post study drug) | 49 % Functional Activity | Standard Deviation 16 |
| Placebo | Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7 | T7 (POD 4) | 66 % Functional Activity | Standard Deviation 17 |
| Placebo | Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7 | T3 (30 minutes on CPB) | 55 % Functional Activity | Standard Deviation 27 |
p-value: 0.982t-test, 2 sided
p-value: <0.001t-test, 2 sided
p-value: 0.001t-test, 2 sided
p-value: 0.003t-test, 2 sided
p-value: 0.84t-test, 2 sided
p-value: 0.475t-test, 2 sided
Secondary
Difference in the Median of the ATIII (Functional Assay) of the Control and ATIII Groups at T4
Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the median of the ATIII (functional assay) of the control and ATIII groups at T4 (just prior to coming off of CPB). Data reported as % Functional Activity, which is calculated as the ability of Antithrombin (AT) to suppress FIIa or FXa in the presence of heparin compared to normograms, and expressed as a percentage.
Time frame: T4 (just prior to coming off of CPB)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anti-thrombin III | Difference in the Median of the ATIII (Functional Assay) of the Control and ATIII Groups at T4 | 78.0 % Functional Activity |
| Placebo | Difference in the Median of the ATIII (Functional Assay) of the Control and ATIII Groups at T4 | 69.0 % Functional Activity |
p-value: 0.048Wilcoxon (Mann-Whitney)
Secondary
Difference in the Median of the D Dimer of the Control and ATIII Groups at T1, T5, T6 and T7
Evidence of decreased activation of the coagulation and fibrinolytic systems represented by a difference in the median of the D dimer of the control and ATIII groups at T1 (Baseline), T5 (Arrival in Intensive Care Unit), T6 (Post-Operative Day 2) and T7 (Post-Operative Day 4).
Time frame: T1, T5, T6 and T7
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anti-thrombin III | Difference in the Median of the D Dimer of the Control and ATIII Groups at T1, T5, T6 and T7 | T1 (Baseline) | 1.1 mcg/ml |
| Anti-thrombin III | Difference in the Median of the D Dimer of the Control and ATIII Groups at T1, T5, T6 and T7 | T5 (Arrival in ICU) | 0.6 mcg/ml |
| Anti-thrombin III | Difference in the Median of the D Dimer of the Control and ATIII Groups at T1, T5, T6 and T7 | T6 (POD 2) | 1.3 mcg/ml |
| Anti-thrombin III | Difference in the Median of the D Dimer of the Control and ATIII Groups at T1, T5, T6 and T7 | T7 (POD 4) | 3.2 mcg/ml |
| Placebo | Difference in the Median of the D Dimer of the Control and ATIII Groups at T1, T5, T6 and T7 | T7 (POD 4) | 5.6 mcg/ml |
| Placebo | Difference in the Median of the D Dimer of the Control and ATIII Groups at T1, T5, T6 and T7 | T1 (Baseline) | 0.9 mcg/ml |
| Placebo | Difference in the Median of the D Dimer of the Control and ATIII Groups at T1, T5, T6 and T7 | T6 (POD 2) | 1.7 mcg/ml |
| Placebo | Difference in the Median of the D Dimer of the Control and ATIII Groups at T1, T5, T6 and T7 | T5 (Arrival in ICU) | 1.0 mcg/ml |
p-value: 0.855Wilcoxon (Mann-Whitney)
p-value: 0.225Wilcoxon (Mann-Whitney)
p-value: 0.313Wilcoxon (Mann-Whitney)
p-value: 0.008Wilcoxon (Mann-Whitney)
Secondary
Evidence of Decreased Inflammation Represented by a Decrease in Inflammatory Markers in the ATIII Group
Evidence of decreased inflammation represented by a decrease in inflammatory markers in the ATIII group.
Time frame: Baseline (T1) to Post-Operative Day 4 (T7)
Population: Laboratory testing not performed.
Secondary
Incidence (Number) of Newly Diagnosed Intracranial Hemorrhage
Study the safety profile of dosing the ATIII by monitoring the incidence (number) of newly diagnosed intracranial hemorrhage
Time frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anti-thrombin III | Incidence (Number) of Newly Diagnosed Intracranial Hemorrhage | 1 participants |
| Placebo | Incidence (Number) of Newly Diagnosed Intracranial Hemorrhage | 3 participants |
p-value: 0.342Fisher Exact
Secondary
Incidence (Number) of Thrombotic Events Documented
Study the safety profile of dosing the ATIII by monitoring the incidence (number) of thrombotic events documented.
Time frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anti-thrombin III | Incidence (Number) of Thrombotic Events Documented | 0 events |
| Placebo | Incidence (Number) of Thrombotic Events Documented | 0 events |
Secondary
Incidence of Extracorporeal Membrane Oxygenation (ECMO) Support Within 24 Hours Postoperatively
Study the safety profile of dosing the ATIII by monitoring the incidence of extracorporeal membrane oxygenation (ECMO) support within 24 hours postoperatively.
Time frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anti-thrombin III | Incidence of Extracorporeal Membrane Oxygenation (ECMO) Support Within 24 Hours Postoperatively | 0 number |
| Placebo | Incidence of Extracorporeal Membrane Oxygenation (ECMO) Support Within 24 Hours Postoperatively | 2 number |
p-value: 0.231Fisher Exact
Secondary
Incidence of Mediastinal Exploration Within 24 Hours Postoperatively
Study the safety profile of dosing the ATIII by monitoring the incidence of mediastinal exploration within 24 hours postoperatively
Time frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anti-thrombin III | Incidence of Mediastinal Exploration Within 24 Hours Postoperatively | 2 count of participants |
| Placebo | Incidence of Mediastinal Exploration Within 24 Hours Postoperatively | 3 count of participants |
p-value: 0.661Fisher Exact
Secondary
Incidence of New Onset Renal Failure, Defined by Stage 3 of the AKIN Criteria
Study the safety profile of dosing the ATIII by monitoring the incidence of new onset renal failure, defined by stage 3 of the Acute Kidney Injury Network (AKIN) criteria. 1. Serum creatinine increase ≥26.5 μmol/l (≥0.3 mg/dl) or increase to 1.5-2.0-fold from baseline, urine output \<0.5 ml/kg/h for 6 hours 2. Serum creatinine increase \>2.0-3.0-fold from baseline, urine output \<0.5 ml/kg/h for 12 hours 3. Serum creatinine increase \>3.0-fold from baseline or serum creatinine ≥354 μmol/l (≥4.0 mg/dl) with an acute increase of at least 44 μmol/l (0.5 mg/dl) or need for Renal replacement therapy (RRT), urine output \<0.3 ml/kg/h for 24 h or anuria for 12 hours or need for RRT
Time frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anti-thrombin III | Incidence of New Onset Renal Failure, Defined by Stage 3 of the AKIN Criteria | 1 count of participants |
| Placebo | Incidence of New Onset Renal Failure, Defined by Stage 3 of the AKIN Criteria | 1 count of participants |
p-value: 1Fisher Exact
Secondary
Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively
Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively
Time frame: Baseline (Intraoperatively)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anti-thrombin III | Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively | 5 count of participants |
| Placebo | Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively | 5 count of participants |
Secondary
Length of Post Operative Ventilation in Days
Length of post operative ventilation in days
Time frame: ICU arrival (Time 5) to Time 7 (Post-Operative Day 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Anti-thrombin III | Length of Post Operative Ventilation in Days | 3.9 days | Standard Deviation 2 |
| Placebo | Length of Post Operative Ventilation in Days | 3.6 days | Standard Deviation 1.3 |
p-value: 0.738t-test, 2 sided
Secondary
Length of Time to Delayed Sternal Closure Measured in Days
Study the safety profile of dosing the ATIII by monitoring the length of time to delayed sternal closure measured in days
Time frame: Baseline (intraoperatively) (Time 1) to Time 7 (Post OP Day 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Anti-thrombin III | Length of Time to Delayed Sternal Closure Measured in Days | 2.7 days | Standard Deviation 2.1 |
| Placebo | Length of Time to Delayed Sternal Closure Measured in Days | 2.7 days | Standard Deviation 2.2 |
p-value: 0.961t-test, 2 sided
Secondary
Number of Total Blood Product Units Transfused 24-hours Post-operatively by Group
Number of total blood product units (including packed Fresh frozen plasma units, Platelet Units, cryo-precipitate units, and Red Blood Cell units) transfused 24 hours post-operatively for each group (not total units transfused for each subject)
Time frame: 24 Hours Post-Operatively
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anti-thrombin III | Number of Total Blood Product Units Transfused 24-hours Post-operatively by Group | 6 Units |
| Placebo | Number of Total Blood Product Units Transfused 24-hours Post-operatively by Group | 19 Units |
p-value: 0.0004Fisher Exact
Secondary
Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group
Number of packed Fresh frozen plasma units, Platelet Units, cryo-precipitate units, and Red Blood Cell units transfused 24 hours post-operatively for each group (not total units transfused for each subject)
Time frame: 24 Hours Post-Operatively
Population: Unable to be calculated accurately as blood products given in CPB prime were only designated in Units administered and not mls (no record of how many mls present in each unit). Therefore unable to back calculate total mls given from start of surgery to 24 hours postop
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anti-thrombin III | Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group | Fresh Frozen Plasma Units | 1 Units |
| Anti-thrombin III | Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group | Platelet Units | 0 Units |
| Anti-thrombin III | Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group | Cryo-Precipitate Units | 0 Units |
| Anti-thrombin III | Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group | Red Blood Cell Units | 5 Units |
| Placebo | Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group | Red Blood Cell Units | 9 Units |
| Placebo | Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group | Fresh Frozen Plasma Units | 3 Units |
| Placebo | Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group | Cryo-Precipitate Units | 3 Units |
| Placebo | Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group | Platelet Units | 4 Units |
Secondary
Protamine Dose Determined by Hemostasis Management System Machine (mg/kg)
Protamine dose determined by Hemostasis Management system machine (mg/kg)
Time frame: T1 (Baseline) to T5 (Arrival in ICU)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anti-thrombin III | Protamine Dose Determined by Hemostasis Management System Machine (mg/kg) | 9.8 mg/kg |
| Placebo | Protamine Dose Determined by Hemostasis Management System Machine (mg/kg) | 10.0 mg/kg |
p-value: 0.545Wilcoxon (Mann-Whitney)
Secondary
Residual Heparin at the ICU Arrival Time Point Represented by a Decreased Anti Factor Xa Level.
Evidence of a decreased amount of residual heparin at the Intensive Care Unit arrival time point (T5) represented by a decreased anti factor Xa level.
Time frame: T5 (Intensive Care Unit Arrival)
Population: In both arms, heparin level was undetectable as Anti factor Xa level was less than or equal to 0.1 IU/ml in all subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Anti-thrombin III | Residual Heparin at the ICU Arrival Time Point Represented by a Decreased Anti Factor Xa Level. | 0.1 International Units/milliter | Standard Deviation 0 |
| Placebo | Residual Heparin at the ICU Arrival Time Point Represented by a Decreased Anti Factor Xa Level. | 0.1 International Units/milliter | Standard Deviation 0 |
Secondary
Time From Protamine Administration to Skin Dressing
Time from protamine administration to skin dressing
Time frame: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anti-thrombin III | Time From Protamine Administration to Skin Dressing | 107.0 minutes |
| Placebo | Time From Protamine Administration to Skin Dressing | 89.0 minutes |
p-value: 0.757Wilcoxon (Mann-Whitney)
Secondary
Total Dose of Heparin While on Cardiopulmonary Bypass
Total dose of Heparin while on Cardiopulmonary Bypass
Time frame: T1 (Baseline) to T5 (Arrival in ICU)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anti-thrombin III | Total Dose of Heparin While on Cardiopulmonary Bypass | 3775 units |
| Placebo | Total Dose of Heparin While on Cardiopulmonary Bypass | 5000 units |
p-value: 0.056Wilcoxon (Mann-Whitney)
Secondary
Total Dose of Recombinant Factor 7a (VIIa) Used Intraoperatively
Total Dose of rescue recombinant factor 7a (VIIa) used intraoperatively
Time frame: Intraoperatively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Anti-thrombin III | Total Dose of Recombinant Factor 7a (VIIa) Used Intraoperatively | 56.1 mcg | Standard Deviation 118.2 |
| Placebo | Total Dose of Recombinant Factor 7a (VIIa) Used Intraoperatively | 70.6 mcg | Standard Deviation 174.1 |
p-value: 0.927t-test, 2 sided
Secondary
Total Volume of Blood Products While on CPB
Total volume of blood products exposed intraoperatively including the pump prime (ml/kg)
Time frame: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Anti-thrombin III | Total Volume of Blood Products While on CPB | Total volume ultrafiltration Platelet transfusion | 89.7 mls | Standard Deviation 44.2 |
| Anti-thrombin III | Total Volume of Blood Products While on CPB | Total Volume Fresh Frozen Plasma | 68.5 mls | Standard Deviation 121.5 |
| Anti-thrombin III | Total Volume of Blood Products While on CPB | Total volume Cryoprecipitate transfusion | 35.4 mls | Standard Deviation 22.8 |
| Anti-thrombin III | Total Volume of Blood Products While on CPB | Total Volume Red Blood Cells | 57 mls | Standard Deviation 103.9 |
| Placebo | Total Volume of Blood Products While on CPB | Total volume Cryoprecipitate transfusion | 33.8 mls | Standard Deviation 32.5 |
| Placebo | Total Volume of Blood Products While on CPB | Total Volume Fresh Frozen Plasma | 141.9 mls | Standard Deviation 133.6 |
| Placebo | Total Volume of Blood Products While on CPB | Total volume ultrafiltration Platelet transfusion | 72.6 mls | Standard Deviation 54 |
| Placebo | Total Volume of Blood Products While on CPB | Total Volume Red Blood Cells | 101.5 mls | Standard Deviation 128.9 |
Secondary
Total Volume of Fresh Frozen Plasma Given Prior to CPB
Total volume of Fresh Frozen Plasma given prior to CPB, including the pump prime (ml/kg)
Time frame: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Anti-thrombin III | Total Volume of Fresh Frozen Plasma Given Prior to CPB | 15 ml/kg | Standard Deviation 67.1 |
| Placebo | Total Volume of Fresh Frozen Plasma Given Prior to CPB | 5.8 ml/kg | Standard Deviation 25.5 |
Secondary
Volume of Postoperative Blood Loss
Volume of postoperative blood loss from 10min post protamine administration to 24 hour post protamine administration- (ml/kg)
Time frame: From 10min post protamine administration to 24 hour post protamine administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Anti-thrombin III | Volume of Postoperative Blood Loss | 24 hour postop Fresh Frozen Plasma exposures | 0.8 ml/kg | Standard Deviation 3.4 |
| Anti-thrombin III | Volume of Postoperative Blood Loss | 24 hour postop Platelet exposures | 0 ml/kg | Standard Deviation 0 |
| Anti-thrombin III | Volume of Postoperative Blood Loss | 24 hour postop Cryoprecipitate exposures | 0 ml/kg | Standard Deviation 0 |
| Anti-thrombin III | Volume of Postoperative Blood Loss | 24 hour postop Red Blood Cell exposures | 3.9 ml/kg | Standard Deviation 7.3 |
| Placebo | Volume of Postoperative Blood Loss | 24 hour postop Red Blood Cell exposures | 10.1 ml/kg | Standard Deviation 16.4 |
| Placebo | Volume of Postoperative Blood Loss | 24 hour postop Fresh Frozen Plasma exposures | 2.8 ml/kg | Standard Deviation 7.3 |
| Placebo | Volume of Postoperative Blood Loss | 24 hour postop Cryoprecipitate exposures | 2.1 ml/kg | Standard Deviation 5.4 |
| Placebo | Volume of Postoperative Blood Loss | 24 hour postop Platelet exposures | 2.7 ml/kg | Standard Deviation 5.6 |
p-value: 0.2741t-test, 2 sided
p-value: 0.0351t-test, 2 sided
p-value: 0.073t-test, 2 sided
p-value: 0.0196t-test, 2 sided