Trial Outcomes & Findings for Anti-thrombin III (ATIII) vs Placebo in Children (<7mo) Undergoing Open Congenital Cardiac Surgery (NCT NCT02103114)

NCT ID: NCT02103114

Last Updated: 2019-11-25

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 45 participants
• Primary outcome timeframe: Time 5 (on arrival in ICU)
• Results posted on: 2019-11-25

Participant Flow

Five subjects enrolled but withdrew prior to randomization

Participant milestones

Measure	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	Placebo Normal saline placebo
Overall Study STARTED	20	20
Overall Study COMPLETED	20	19
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Anti-thrombin III n=20 Participants 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 n=20 Participants Placebo: Normal saline placebo	Total n=40 Participants Total of all reporting groups
Age, Continuous	9.8 days STANDARD_DEVIATION 19.7 • n=5 Participants	17.2 days STANDARD_DEVIATION 30.2 • n=7 Participants	14.6 days STANDARD_DEVIATION 26.1 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants	20 participants n=7 Participants	40 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline 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 12	54 % Functional Activity Standard Deviation 13
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	49 % Functional Activity Standard Deviation 16
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	55 % Functional Activity Standard Deviation 27
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	63 % Functional Activity Standard Deviation 19
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	57 % Functional Activity Standard Deviation 14
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	66 % Functional Activity Standard Deviation 17

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
Difference in the Median of the ATIII (Functional Assay) of the Control and ATIII Groups at T4	78.0 % Functional Activity Interval 69.5 to 95.0	69.0 % Functional Activity Interval 35.0 to 89.0

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
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 Interval 0.7 to 1.5	0.9 mcg/ml Interval 0.7 to 1.9
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 Interval 0.5 to 0.9	1.0 mcg/ml Interval 0.6 to 1.5
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 Interval 0.9 to 2.0	1.7 mcg/ml Interval 1.0 to 2.9
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 Interval 2.5 to 4.3	5.6 mcg/ml Interval 4.3 to 8.4

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline 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	0.1 International Units/milliter Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline (T1) to Post-Operative Day 4 (T7)

Population: Laboratory testing not performed.

Evidence of decreased inflammation represented by a decrease in inflammatory markers in the ATIII group.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: T1 (Baseline) to T5 (Arrival in ICU)

Total dose of Heparin while on Cardiopulmonary Bypass

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
Total Dose of Heparin While on Cardiopulmonary Bypass	3775 units Interval 3400.0 to 5700.0	5000 units Interval 4200.0 to 6300.0

SECONDARY outcome

Timeframe: T1 (Baseline) to T5 (Arrival in ICU)

Protamine dose determined by Hemostasis Management system machine (mg/kg)

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
Protamine Dose Determined by Hemostasis Management System Machine (mg/kg)	9.8 mg/kg Interval 9.1 to 10.1	10.0 mg/kg Interval 6.5 to 10.7

SECONDARY outcome

Timeframe: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4)

Total volume of blood products exposed intraoperatively including the pump prime (ml/kg)

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
Total Volume of Blood Products While on CPB Total Volume Red Blood Cells	57 mls Standard Deviation 103.9	101.5 mls Standard Deviation 128.9
Total Volume of Blood Products While on CPB Total Volume Fresh Frozen Plasma	68.5 mls Standard Deviation 121.5	141.9 mls Standard Deviation 133.6
Total Volume of Blood Products While on CPB Total volume ultrafiltration Platelet transfusion	89.7 mls Standard Deviation 44.2	72.6 mls Standard Deviation 54
Total Volume of Blood Products While on CPB Total volume Cryoprecipitate transfusion	35.4 mls Standard Deviation 22.8	33.8 mls Standard Deviation 32.5

SECONDARY outcome

Timeframe: Baseline (intraoperatively) (Time 1) to before termination of bypass (Time 4)

Time from protamine administration to skin dressing

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
Time From Protamine Administration to Skin Dressing	107.0 minutes Interval 65.0 to 123.0	89.0 minutes Interval 60.0 to 155.0

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
Total Volume of Fresh Frozen Plasma Given Prior to CPB	15 ml/kg Standard Deviation 67.1	5.8 ml/kg Standard Deviation 25.5

SECONDARY outcome

Timeframe: Baseline (Intraoperatively)

Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
Incidence of Recombinant Factor 7a (VIIa) Use Intraoperatively	5 count of participants	5 count of participants

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
Volume of Postoperative Blood Loss 24 hour postop Platelet exposures	0 ml/kg Standard Deviation 0	2.7 ml/kg Standard Deviation 5.6
Volume of Postoperative Blood Loss 24 hour postop Fresh Frozen Plasma exposures	0.8 ml/kg Standard Deviation 3.4	2.8 ml/kg Standard Deviation 7.3
Volume of Postoperative Blood Loss 24 hour postop Cryoprecipitate exposures	0 ml/kg Standard Deviation 0	2.1 ml/kg Standard Deviation 5.4
Volume of Postoperative Blood Loss 24 hour postop Red Blood Cell exposures	3.9 ml/kg Standard Deviation 7.3	10.1 ml/kg Standard Deviation 16.4

SECONDARY outcome

Timeframe: protamine time plus 24 hours

Chest Tube output (protamine time plus 24 hours) in milliliters

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
Chest Tube Output (Protamine Time Plus 24 Hours) in Milliliters	59.0 milliters Interval 46.5 to 83.5	113.0 milliters Interval 67.0 to 210.0

SECONDARY outcome

Timeframe: 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

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)

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group Fresh Frozen Plasma Units	1 Units	3 Units
Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group Platelet Units	0 Units	4 Units
Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group Cryo-Precipitate Units	0 Units	3 Units
Number of Total Blood Product Units Transfused by Type 24-hours Post-operatively by Group Red Blood Cell Units	5 Units	9 Units

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
Number of Total Blood Product Units Transfused 24-hours Post-operatively by Group	6 Units	19 Units

SECONDARY outcome

Timeframe: Intraoperatively

Total Dose of rescue recombinant factor 7a (VIIa) used intraoperatively

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
Total Dose of Recombinant Factor 7a (VIIa) Used Intraoperatively	56.1 mcg Standard Deviation 118.2	70.6 mcg Standard Deviation 174.1

SECONDARY outcome

Timeframe: ICU arrival (Time 5) to Time 7 (Post-Operative Day 4)

Length of post operative ventilation in days

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
Length of Post Operative Ventilation in Days	3.9 days Standard Deviation 2	3.6 days Standard Deviation 1.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
Incidence of Extracorporeal Membrane Oxygenation (ECMO) Support Within 24 Hours Postoperatively	0 number	2 number

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
Incidence of Mediastinal Exploration Within 24 Hours Postoperatively	2 count of participants	3 count of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
Incidence (Number) of Thrombotic Events Documented	0 events	0 events

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
Incidence of New Onset Renal Failure, Defined by Stage 3 of the AKIN Criteria	1 count of participants	1 count of participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
Incidence (Number) of Newly Diagnosed Intracranial Hemorrhage	1 participants	3 participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Anti-thrombin III n=20 Participants 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 n=19 Participants Normal saline placebo
Length of Time to Delayed Sternal Closure Measured in Days	2.7 days Standard Deviation 2.1	2.7 days Standard Deviation 2.2

Adverse Events

Anti-thrombin III

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo

Serious events: 8 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Anti-thrombin III n=20 participants at risk 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 n=20 participants at risk Normal saline placebo
Surgical and medical procedures Bradycardia	5.0% 1/20 • Number of events 1 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Surgical and medical procedures Hypotension	5.0% 1/20 • Number of events 1 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Respiratory, thoracic and mediastinal disorders ECMO	5.0% 1/20 • Number of events 1 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Blood and lymphatic system disorders Intraop Bleeding	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	20.0% 4/20 • Number of events 4 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Cardiac disorders Hypotension R/T chest fluid retention (not bleeding)	5.0% 1/20 • Number of events 1 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Cardiac disorders Cardiac arrest	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	5.0% 1/20 • Number of events 1 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Nervous system disorders Right-sided tonic clonic seizure	5.0% 1/20 • Number of events 1 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Blood and lymphatic system disorders Hypotension R/T bleeding	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	5.0% 1/20 • Number of events 1 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Blood and lymphatic system disorders Shock	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	5.0% 1/20 • Number of events 1 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Nervous system disorders Right-sided subdural hematoma	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	5.0% 1/20 • Number of events 1 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Surgical and medical procedures Hemorrhage	5.0% 1/20 • Number of events 1 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	5.0% 1/20 • Number of events 1 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.

Other adverse events

Measure	Anti-thrombin III n=20 participants at risk 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 n=20 participants at risk Normal saline placebo
Cardiac disorders Junctional ectopic tachycardia	5.0% 1/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Cardiac disorders Junctional rhythm tachycardia	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	5.0% 1/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Gastrointestinal disorders Hematochezia	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	5.0% 1/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Blood and lymphatic system disorders Anemia	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	5.0% 1/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Blood and lymphatic system disorders Low Hematocrit	5.0% 1/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Blood and lymphatic system disorders Desaturation	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	5.0% 1/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Blood and lymphatic system disorders Intermittent PVCs R/T Low K, Low Mg	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	5.0% 1/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Cardiac disorders SVTs	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	5.0% 1/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Nervous system disorders Echogenic focus in occipital parietal region	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	5.0% 1/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Cardiac disorders Hypotension	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	5.0% 1/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Blood and lymphatic system disorders Hemoparitoneum	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	5.0% 1/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Nervous system disorders Posterior subdural hematoma	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	5.0% 1/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Renal and urinary disorders Acute kidney injury	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	5.0% 1/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.
Respiratory, thoracic and mediastinal disorders Right Lung Collapse	5.0% 1/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.	0.00% 0/20 • Adverse events were collected from Baseline (intraoperatively) until post-operative day four.

Additional Information

Dr. Edmund Jooste

Duke University

Phone: 919-681-4877

Email: edmund.jooste@duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place