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Trial record 7 of 10 for:    "Hereditary Antithrombin Deficiency" | "Antithrombin III"

Anti-thrombin III (ATIII) vs Placebo in Children (<7mo) Undergoing Open Congenital Cardiac Surgery

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ClinicalTrials.gov Identifier: NCT02103114
Recruitment Status : Completed
First Posted : April 3, 2014
Results First Posted : July 26, 2017
Last Update Posted : December 27, 2018
Sponsor:
Collaborator:
Grifols Biologicals, LLC
Information provided by (Responsible Party):
Duke University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition ATIII Deficiency
Interventions Drug: Anti-thrombin III
Other: Placebo
Enrollment 45
Recruitment Details Five subjects enrolled but withdrew prior to randomization
Pre-assignment Details  
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description

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

Normal saline placebo
Period Title: Overall Study
Started 20 20
Completed 20 19
Not Completed 0 1
Arm/Group Title Anti-thrombin III Placebo Total
Hide Arm/Group Description

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

Placebo: Normal saline placebo Total of all reporting groups
Overall Number of Baseline Participants 20 20 40
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 20 participants 20 participants 40 participants
9.8  (19.7) 17.2  (30.2) 14.6  (26.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 20 participants 40 participants
Female
6
  30.0%
7
  35.0%
13
  32.5%
Male
14
  70.0%
13
  65.0%
27
  67.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 20 participants 20 participants 40 participants
20 20 40
1.Primary Outcome
Title 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)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The laboratory was unable to perform this blood assay due to technical issues and no results were generated.
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Normal saline placebo
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
2.Secondary Outcome
Title 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)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The laboratory was unable to perform this blood assay due to technical difficulties and no results were generated.
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Normal saline placebo
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Difference in the Mean the ATIII (Functional Assay) of the Control and ATIII Groups at T1, T2, T3, T5, T6 and T7
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Normal saline placebo
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: % Functional Activity
T1 (Baseline) 54  (12) 54  (13)
T2 (30 minutes post study drug) 99  (19) 49  (16)
T3 (30 minutes on CPB) 83  (20) 55  (27)
T5 (Arrival in ICU) 82  (18) 63  (19)
T6 (POD 2) 58  (15) 57  (14)
T7 (POD 4) 70.7  (20) 66  (17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments T1 (Baseline)
Statistical Test of Hypothesis P-Value 0.982
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments T2 (30 minutes after study drug)
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments T3 (30 minutes on CPB)
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments T5 (Arrival in ICU)
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments T6 (POD 2)
Statistical Test of Hypothesis P-Value 0.840
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments T7 (POD 4)
Statistical Test of Hypothesis P-Value 0.475
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
4.Secondary Outcome
Title Difference in the Median of the ATIII (Functional Assay) of the Control and ATIII Groups at T4
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Placebo: Normal saline placebo
Overall Number of Participants Analyzed 20 19
Median (Inter-Quartile Range)
Unit of Measure: % Functional Activity
78.0
(69.5 to 95.0)
69.0
(35.0 to 89.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments T4 (just prior to coming off of CPB)
Statistical Test of Hypothesis P-Value 0.048
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
5.Secondary Outcome
Title Difference in the Median of the D Dimer of the Control and ATIII Groups at T1, T5, T6 and T7
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Normal saline placebo
Overall Number of Participants Analyzed 20 19
Median (Inter-Quartile Range)
Unit of Measure: mcg/ml
T1 (Baseline)
1.1
(0.7 to 1.5)
0.9
(0.7 to 1.9)
T5 (Arrival in ICU)
0.6
(0.5 to 0.9)
1.0
(0.6 to 1.5)
T6 (POD 2)
1.3
(0.9 to 2.0)
1.7
(1.0 to 2.9)
T7 (POD 4)
3.2
(2.5 to 4.3)
5.6
(4.3 to 8.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments T1 (Baseline)
Statistical Test of Hypothesis P-Value 0.855
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments T5 (Arrival in ICU)
Statistical Test of Hypothesis P-Value 0.225
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments T6 (POD 2)
Statistical Test of Hypothesis P-Value 0.313
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments T7 (POD 4)
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
6.Secondary Outcome
Title Residual Heparin at the ICU Arrival Time Point Represented by a Decreased Anti Factor Xa Level.
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Placebo: Normal saline placebo
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: International Units/milliter
0.1  (0) 0.1  (0)
7.Secondary Outcome
Title Evidence of Decreased Inflammation Represented by a Decrease in Inflammatory Markers in the ATIII Group
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Laboratory testing not performed.
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Placebo: Normal saline placebo
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Total Dose of Heparin While on Cardiopulmonary Bypass
Hide Description Total dose of Heparin while on Cardiopulmonary Bypass
Time Frame T1 (Baseline) to T5 (Arrival in ICU)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Normal saline placebo
Overall Number of Participants Analyzed 20 19
Median (Inter-Quartile Range)
Unit of Measure: units
3775
(3400.0 to 5700.0)
5000
(4200.0 to 6300.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments T1 (Baseline) to T5 (Arrival in ICU)
Statistical Test of Hypothesis P-Value 0.056
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
9.Secondary Outcome
Title Protamine Dose Determined by Hemostasis Management System Machine (mg/kg)
Hide Description Protamine dose determined by Hemostasis Management system machine (mg/kg)
Time Frame T1 (Baseline) to T5 (Arrival in ICU)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Normal saline placebo
Overall Number of Participants Analyzed 20 19
Median (Inter-Quartile Range)
Unit of Measure: mg/kg
9.8
(9.1 to 10.1)
10.0
(6.5 to 10.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments T1 (Baseline) to T5 (Arrival in ICU)
Statistical Test of Hypothesis P-Value 0.545
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
10.Secondary Outcome
Title Total Volume of Blood Products While on CPB
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Normal saline placebo
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: mls
Total Volume Red Blood Cells 57  (103.9) 101.5  (128.9)
Total Volume Fresh Frozen Plasma 68.5  (121.5) 141.9  (133.6)
Total volume ultrafiltration Platelet transfusion 89.7  (44.2) 72.6  (54)
Total volume Cryoprecipitate transfusion 35.4  (22.8) 33.8  (32.5)
11.Secondary Outcome
Title Time From Protamine Administration to Skin Dressing
Hide Description Time from protamine administration to skin dressing
Time Frame Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Normal saline placebo
Overall Number of Participants Analyzed 20 19
Median (Inter-Quartile Range)
Unit of Measure: minutes
107.0
(65.0 to 123.0)
89.0
(60.0 to 155.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4)
Statistical Test of Hypothesis P-Value 0.757
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
12.Secondary Outcome
Title Total Volume of Fresh Frozen Plasma Given Prior to CPB
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Placebo: Normal saline placebo
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: ml/kg
15  (67.1) 5.8  (25.5)
13.Secondary Outcome
Title Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively
Hide Description Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively
Time Frame Baseline (Intraoperatively)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Placebo: Normal saline placebo
Overall Number of Participants Analyzed 20 19
Measure Type: Number
Unit of Measure: count of participants
5 5
14.Secondary Outcome
Title Volume of Postoperative Blood Loss
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Normal saline placebo
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: ml/kg
24 hour postop Fresh Frozen Plasma exposures 0.8  (3.4) 2.8  (7.3)
24 hour postop Platelet exposures 0  (0) 2.7  (5.6)
24 hour postop Cryoprecipitate exposures 0  (0) 2.1  (5.4)
24 hour postop Red Blood Cell exposures 3.9  (7.3) 10.1  (16.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2741
Comments [Not Specified]
Method t-test, 2 sided
Comments 24 hour postop Fresh Frozen Plasma exposures
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0351
Comments [Not Specified]
Method t-test, 2 sided
Comments 24 hour postop Platelet exposures
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.073
Comments [Not Specified]
Method t-test, 2 sided
Comments 24 hour postop Cryoprecipitate exposures
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0196
Comments [Not Specified]
Method t-test, 2 sided
Comments 24 hour postop Red Blood Cell exposures
15.Secondary Outcome
Title Chest Tube Output (Protamine Time Plus 24 Hours) in Milliliters
Hide Description Chest Tube output (protamine time plus 24 hours) in milliliters
Time Frame protamine time plus 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Placebo: Normal saline placebo
Overall Number of Participants Analyzed 20 19
Median (Inter-Quartile Range)
Unit of Measure: milliters
59.0
(46.5 to 83.5)
113.0
(67.0 to 210.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments protamine time plus 24 hours
Statistical Test of Hypothesis P-Value 0.016
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
16.Secondary Outcome
Title Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Normal saline placebo
Overall Number of Participants Analyzed 20 19
Measure Type: Number
Unit of Measure: Units
Fresh Frozen Plasma Units 1 3
Platelet Units 0 4
Cryo-Precipitate Units 0 3
Red Blood Cell Units 5 9
17.Secondary Outcome
Title Number of Total Blood Product Units Transfused 24-hours Post-operatively by Group
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Placebo: Normal saline placebo
Overall Number of Participants Analyzed 20 19
Measure Type: Number
Unit of Measure: Units
6 19
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Equivalence
Comments 24 Hours Post-Operatively
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
18.Secondary Outcome
Title Total Dose of Recombinant Factor 7a (VIIa) Used Intraoperatively
Hide Description Total Dose of rescue recombinant factor 7a (VIIa) used intraoperatively
Time Frame Intraoperatively
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Normal saline placebo
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: mcg
56.1  (118.2) 70.6  (174.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.927
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
19.Secondary Outcome
Title Length of Post Operative Ventilation in Days
Hide Description Length of post operative ventilation in days
Time Frame ICU arrival (Time 5) to Time 7 (Post-Operative Day 4)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Normal saline placebo
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: days
3.9  (2) 3.6  (1.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.738
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
20.Secondary Outcome
Title Incidence of Extracorporeal Membrane Oxygenation (ECMO) Support Within 24 Hours Postoperatively
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Normal saline placebo
Overall Number of Participants Analyzed 20 19
Measure Type: Number
Unit of Measure: number
0 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.231
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
21.Secondary Outcome
Title Incidence of Mediastinal Exploration Within 24 Hours Postoperatively
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Normal saline placebo
Overall Number of Participants Analyzed 20 19
Measure Type: Number
Unit of Measure: count of participants
2 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.661
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
22.Secondary Outcome
Title Incidence (Number) of Thrombotic Events Documented
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Normal saline placebo
Overall Number of Participants Analyzed 20 19
Measure Type: Number
Unit of Measure: events
0 0
23.Secondary Outcome
Title Incidence of New Onset Renal Failure, Defined by Stage 3 of the AKIN Criteria
Hide Description

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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Normal saline placebo
Overall Number of Participants Analyzed 20 19
Measure Type: Number
Unit of Measure: count of participants
1 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
24.Secondary Outcome
Title Incidence (Number) of Newly Diagnosed Intracranial Hemorrhage
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Normal saline placebo
Overall Number of Participants Analyzed 20 19
Measure Type: Number
Unit of Measure: participants
1 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.342
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
25.Secondary Outcome
Title Length of Time to Delayed Sternal Closure Measured in Days
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description:

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

Normal saline placebo
Overall Number of Participants Analyzed 20 19
Mean (Standard Deviation)
Unit of Measure: days
2.7  (2.1) 2.7  (2.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anti-thrombin III, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.961
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Time Frame Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Anti-thrombin III Placebo
Hide Arm/Group Description

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

Normal saline placebo
All-Cause Mortality
Anti-thrombin III Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Anti-thrombin III Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/20 (15.00%)      8/20 (40.00%)    
Blood and lymphatic system disorders     
Hypotension R/T bleeding   0/20 (0.00%)  0 1/20 (5.00%)  1
Shock   0/20 (0.00%)  0 1/20 (5.00%)  1
Intraop Bleeding   0/20 (0.00%)  0 4/20 (20.00%)  4
Cardiac disorders     
Hypotension R/T chest fluid retention (not bleeding)   1/20 (5.00%)  1 0/20 (0.00%)  0
Cardiac arrest   0/20 (0.00%)  0 1/20 (5.00%)  1
Nervous system disorders     
Right-sided tonic clonic seizure   1/20 (5.00%)  1 0/20 (0.00%)  0
Right-sided subdural hematoma   0/20 (0.00%)  0 1/20 (5.00%)  1
Respiratory, thoracic and mediastinal disorders     
ECMO   1/20 (5.00%)  1 0/20 (0.00%)  0
Surgical and medical procedures     
Hemorrhage   1/20 (5.00%)  1 1/20 (5.00%)  1
Bradycardia   1/20 (5.00%)  1 0/20 (0.00%)  0
Hypotension   1/20 (5.00%)  1 0/20 (0.00%)  0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Anti-thrombin III Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/20 (15.00%)      7/20 (35.00%)    
Blood and lymphatic system disorders     
Anemia   0/20 (0.00%)  1/20 (5.00%) 
Low Hematocrit   1/20 (5.00%)  0/20 (0.00%) 
Desaturation   0/20 (0.00%)  1/20 (5.00%) 
Intermittent PVCs R/T Low K, Low Mg   0/20 (0.00%)  1/20 (5.00%) 
Hemoparitoneum   0/20 (0.00%)  1/20 (5.00%) 
Cardiac disorders     
Junctional ectopic tachycardia   1/20 (5.00%)  0/20 (0.00%) 
Junctional rhythm tachycardia   0/20 (0.00%)  1/20 (5.00%) 
SVTs   0/20 (0.00%)  1/20 (5.00%) 
Hypotension   0/20 (0.00%)  1/20 (5.00%) 
Gastrointestinal disorders     
Hematochezia   0/20 (0.00%)  1/20 (5.00%) 
Nervous system disorders     
Echogenic focus in occipital parietal region   0/20 (0.00%)  1/20 (5.00%) 
Posterior subdural hematoma   0/20 (0.00%)  1/20 (5.00%) 
Renal and urinary disorders     
Acute kidney injury   0/20 (0.00%)  1/20 (5.00%) 
Respiratory, thoracic and mediastinal disorders     
Right Lung Collapse   1/20 (5.00%)  0/20 (0.00%) 
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Edmund Jooste
Organization: Duke University
Phone: 919-681-4877
EMail: edmund.jooste@duke.edu
Layout table for additonal information
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT02103114     History of Changes
Other Study ID Numbers: Pro00051186
First Submitted: April 1, 2014
First Posted: April 3, 2014
Results First Submitted: April 26, 2017
Results First Posted: July 26, 2017
Last Update Posted: December 27, 2018