Trial Outcomes & Findings for Use of Antithrombin in Cardiac Surgery With Cardiopulmonary Bypass (NCT NCT00823082)

NCT ID: NCT00823082

Last Updated: 2016-09-20

Results Overview

Measurement of postoperative ATIII functional activity at ICU admission

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 200 participants
• Primary outcome timeframe: ICU admission
• Results posted on: 2016-09-20

Participant Flow

Participant milestones

Measure	Antithrombin III Treatment Group Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120%	Control Group No preoperative ATIII supplementation administered
Overall Study STARTED	100	100
Overall Study Safety Population	100	99
Overall Study Intent-to-Treat/Per Protocol Populations	100	94
Overall Study COMPLETED	100	99
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Use of Antithrombin in Cardiac Surgery With Cardiopulmonary Bypass

Baseline characteristics by cohort

Measure	Antithrombin III Treatment Group n=100 Participants Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120%	Control Group n=94 Participants No preoperative ATIII supplementation administered	Total n=194 Participants Total of all reporting groups
Age, Continuous	66.51 years STANDARD_DEVIATION 10.48 • n=5 Participants	67.63 years STANDARD_DEVIATION 11.18 • n=7 Participants	67.05 years STANDARD_DEVIATION 10.81 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	24 Participants n=7 Participants	41 Participants n=5 Participants
Sex: Female, Male Male	83 Participants n=5 Participants	70 Participants n=7 Participants	153 Participants n=5 Participants
Region of Enrollment Italy	100 participants n=5 Participants	94 participants n=7 Participants	194 participants n=5 Participants

PRIMARY outcome

Timeframe: ICU admission

Population: Intent-to-treat set and Per-protocol set

Measurement of postoperative ATIII functional activity at ICU admission

Outcome measures

Measure	Antithrombin III Treatment Group n=100 Participants Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120%	Control Group n=94 Participants No preoperative ATIII supplementation administered
Postoperative ATIII Levels at the ICU Admission	94.06 IU Standard Deviation 13.74	64.70 IU Standard Deviation 9.89

PRIMARY outcome

Timeframe: ICU admission

Population: Intent-to treat set and Per-protocol set

Percentage of subjects with ATIII levels of 58% functional activity or higher at ICU admission

Outcome measures

Measure	Antithrombin III Treatment Group n=100 Participants Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120%	Control Group n=94 Participants No preoperative ATIII supplementation administered
Percentage of Subjects With ATIII Levels of 58% or Higher at ICU Admission	100.0 percentage of participants	74.5 percentage of participants

SECONDARY outcome

Timeframe: During ICU stay (maximum 70 days)

Population: Intent-to-treat set

Percentage of subjects with postoperative myocardial infarction defined through enzymatic criteria plus new Q-waves at the electrocardiogram

Outcome measures

Measure	Antithrombin III Treatment Group n=100 Participants Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120%	Control Group n=94 Participants No preoperative ATIII supplementation administered
Percentage of Subjects With Postoperative Myocardial Infarction Follow-up visit (Anbinex n=76, Control n=69)	0.0 percentage of participants	0.0 percentage of participants
Percentage of Subjects With Postoperative Myocardial Infarction ICU discharge visit (Anbinex n=99, Control n=93)	1.0 percentage of participants	2.2 percentage of participants

SECONDARY outcome

Timeframe: During ICU stay (maximum 70 days)

Population: Intent-to-treat set

Percentage of subjects with adverse neurologic outcome defined as: coma, stroke or psychotic behaviors lasting >12 hours after extubation

Outcome measures

Measure	Antithrombin III Treatment Group n=100 Participants Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120%	Control Group n=94 Participants No preoperative ATIII supplementation administered
Percentage of Subjects With Adverse Neurologic Outcome Follow-up visit (Anbinex n=75, Control n=69)	5.3 percentage of participants	0.0 percentage of participants
Percentage of Subjects With Adverse Neurologic Outcome ICU discharge visit (Anbinex n=99, Control n=93)	1.0 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: During ICU stay (maximum 70 days)

Population: Intent-to-treat set

Percentage of subjects with thromboembolic events defined as perioperative myocardial infarction, stroke, mesenteric infarction, peripheral thromboembolism and pulmonary embolism

Outcome measures

Measure	Antithrombin III Treatment Group n=100 Participants Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120%	Control Group n=94 Participants No preoperative ATIII supplementation administered
Percentage of Patients With Thromboembolic Events Follow-up visit (Anbinex n=76, Control n=69)	0.0 percentage of participants	0.0 percentage of participants
Percentage of Patients With Thromboembolic Events ICU discharge visit (Anbinex n=99, Control n=94)	0.0 percentage of participants	1.1 percentage of participants

SECONDARY outcome

Timeframe: During ICU stay (maximum 70 days)

Population: Intent-to-treat set. One subject in the control group was missing this data.

Outcome measures

Measure	Antithrombin III Treatment Group n=100 Participants Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120%	Control Group n=93 Participants No preoperative ATIII supplementation administered
ICU Stay Duration	2.00 days Interval 1.0 to 4.0	2.00 days Interval 1.0 to 3.0

SECONDARY outcome

Timeframe: 70 days after ICU admission (maximum)

Population: Intent-to-treat set. One subject in the control group was missing this data.

Outcome measures

Measure	Antithrombin III Treatment Group n=100 Participants Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120%	Control Group n=93 Participants No preoperative ATIII supplementation administered
In-hospital Postoperative Mortality	1.0 percentage of participants	1.1 percentage of participants

SECONDARY outcome

Timeframe: Immediately after anesthesia induction

Population: Intent-to-treat set. One subject in the Antithrombin III treatment group was missing this data.

Percentage of subjects with heparin resistance defined as failure to reach an activated clotting time >450 seconds after a dose of up to 400 IU/kg of heparin, or failure to maintain this activated clotting time value despite heparin supplementations of 100 IU/kg per each dose with an interval of at least 30 minutes between doses

Outcome measures

Measure	Antithrombin III Treatment Group n=99 Participants Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120%	Control Group n=94 Participants No preoperative ATIII supplementation administered
Heparin Resistance	17.2 percentage of participants	40.4 percentage of participants

SECONDARY outcome

Timeframe: ICU admission through 12 hours post-operative

Population: Intent-to-treat set. One subject in the Antithrombin III treatment group was missing this data.

Blood loss defined as the amount of blood collected in the cardiotomy reservoir from ICU admission through the following 12 hours

Outcome measures

Measure	Antithrombin III Treatment Group n=99 Participants Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120%	Control Group n=94 Participants No preoperative ATIII supplementation administered
Postoperative Blood Loss in First 12 Hours	516.11 mL Standard Error 30.292	415.00 mL Standard Error 31.087

SECONDARY outcome

Timeframe: During ICU stay (maximum 70 days)

Population: Intent-to-treat set

Number of units of packed red blood cells, fresh frozen plasma, and/or platelets needed

Outcome measures

Measure	Antithrombin III Treatment Group n=100 Participants Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120%	Control Group n=94 Participants No preoperative ATIII supplementation administered
Need for Blood Products Packed Red Blood Cells (Anbinex n=45,Control n=38)	43.711 Units Standard Error 3.551	41.987 Units Standard Error 3.864
Need for Blood Products Fresh frozen plasma (Anbinex n=16, Control n=8)	12.188 Units Standard Error 1.646	13.125 Units Standard Error 2.327
Need for Blood Products Platelets (Anbinex n=5, Control n=8)	8.500 Units Standard Error 1.564	6.188 Units Standard Error 1.236

SECONDARY outcome

Timeframe: During ICU stay (maximum 70 days)

Population: Intent-to-treat set. Two subjects in the Antithrombin III treatment group and 2 subjects in the Control group were missing this data.

Percentage of subjects needing surgical re-exploration resulting from bleeding

Outcome measures

Measure	Antithrombin III Treatment Group n=98 Participants Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120%	Control Group n=92 Participants No preoperative ATIII supplementation administered
Percentage of Subjects Needing Surgical Re-exploration	5.1 percentage of participants	2.2 percentage of participants

SECONDARY outcome

Timeframe: During ICU stay (maximum 70 days)

Population: Intent-to-treat set. Three subjects in the Antithrombin III treatment group and 1 subject in the Control group were missing this data.

Percentage of subjects with low cardiac syndrome defined as the need for major inotropic support or intra-aortic balloon pump

Outcome measures

Measure	Antithrombin III Treatment Group n=97 Participants Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120%	Control Group n=93 Participants No preoperative ATIII supplementation administered
Percentage of Subjects With Low Cardiac Syndrome	24.7 percentage of participants	20.4 percentage of participants

SECONDARY outcome

Timeframe: During ICU stay (maximum 70 days)

Population: Intent-to-treat set

Percentage of subjects with renal dysfunction defined as an increase of serum creatinine levels to >2.0 and twice the baseline level or need for renal replacement therapy

Outcome measures

Measure	Antithrombin III Treatment Group n=100 Participants Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120%	Control Group n=94 Participants No preoperative ATIII supplementation administered
Percentage of Subjects With Renal Dysfunction Follow-up visit (Anbinex n=75, Control n=69)	1.3 Percentage of participants	0.0 Percentage of participants
Percentage of Subjects With Renal Dysfunction ICU discharge visit (Anbinex n=99, Control n=93)	3.0 Percentage of participants	1.1 Percentage of participants

SECONDARY outcome

Timeframe: During ICU stay (maximum 70 days)

Population: Intent-to-treat set

Outcome measures

Measure	Antithrombin III Treatment Group n=100 Participants Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120%	Control Group n=94 Participants No preoperative ATIII supplementation administered
Mechanical Ventilation Duration	1.00 Days Interval 1.0 to 1.0	1.00 Days Interval 1.0 to 1.0

SECONDARY outcome

Timeframe: During ICU stay (maximum 70 days)

Length of hospital stay (days) in both groups was defined as the discharge date minus the surgery date plus 1 day, during a maximum of 70 days after ICU admission.

Outcome measures

Measure	Antithrombin III Treatment Group n=100 Participants Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120%	Control Group n=94 Participants No preoperative ATIII supplementation administered
Length of Hospital Stay	10.00 days Interval 8.0 to 13.5	10.00 days Interval 8.0 to 13.0

Adverse Events

Antithrombin III Treatment Group

Serious events: 32 serious events

Other events: 96 other events

Deaths: 0 deaths

Control Group

Serious events: 29 serious events

Other events: 97 other events

Deaths: 0 deaths

Serious adverse events

Measure	Antithrombin III Treatment Group n=100 participants at risk Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120%	Control Group n=99 participants at risk No preoperative ATII supplementation administered
Blood and lymphatic system disorders Leukocytosis	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Cardiac disorders Atrial fibrillation	22.0% 22/100 • Number of events 22 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	17.2% 17/99 • Number of events 17 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Cardiac disorders Atrial flutter	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Cardiac disorders Bradycardia	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	2.0% 2/99 • Number of events 2 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Cardiac disorders Cardiac arrest	2.0% 2/100 • Number of events 3 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Cardiac disorders Cardiac tamponade	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	2.0% 2/99 • Number of events 2 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Cardiac disorders Low cardiac output syndrome	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	3.0% 3/99 • Number of events 3 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Cardiac disorders Myocardial infarction	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Cardiac disorders Ventricular fibrillation	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	2.0% 2/99 • Number of events 2 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Cardiac disorders Ventricular hypokinesia	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
General disorders Device occlusion	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
General disorders Hyperpyrexia	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
General disorders Pyrexia	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Infections and infestations Acinetobacter infection	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Infections and infestations Endocarditis	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Infections and infestations Klebsiella infection	2.0% 2/100 • Number of events 2 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Infections and infestations Pseudomonas infection	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Infections and infestations Sepsis	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Infections and infestations Serratia infection	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Infections and infestations Staphyloccal infection	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Infections and infestations Wound infection Staphyloccal	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Injury, poisoning and procedural complications Graft thrombosis	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Injury, poisoning and procedural complications Post procedural hemorrhage	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Injury, poisoning and procedural complications Vasoplegia syndrome	2.0% 2/100 • Number of events 2 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Injury, poisoning and procedural complications Wound secretion	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Investigations Electrocardiogram ST segment elevation	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Investigations Enterococcus test positive	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Investigations Seroconversion test	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Investigations Staphylcoccus test positive	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Musculoskeletal and connective tissue disorders Muscle necrosis	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Nervous system disorders Cerebral hematoma	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Nervous system disorders Cerebral hemorrhage	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Nervous system disorders Coma	2.0% 2/100 • Number of events 2 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Psychiatric disorders Psychotic behavior	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Renal and urinary disorders Oliguria	2.0% 2/100 • Number of events 2 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Renal and urinary disorders Renal failure	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Respiratory, thoracic and mediastinal disorders Acute pulmonary edema	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.0% 2/100 • Number of events 2 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	2.0% 2/99 • Number of events 2 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Surgical and medical procedures Evidence based treatment	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	2.0% 2/99 • Number of events 2 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Surgical and medical procedures Hospitalization	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Surgical and medical procedures Tricuspid valve repair	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Vascular disorders Hemodynamic instability	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Vascular disorders Hemorrhage	2.0% 2/100 • Number of events 2 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Vascular disorders Hypertension	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Vascular disorders Hypotension	1.0% 1/100 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Infections and infestations Septic shock	2.0% 2/100 • Number of events 2 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.

Other adverse events

Measure	Antithrombin III Treatment Group n=100 participants at risk Preoperative ATIII supplementation administered immediately after anesthesia induction Antithrombin III: Single dose of antithrombin III sufficient to achieve a preoperative level of 120%	Control Group n=99 participants at risk No preoperative ATII supplementation administered
Blood and lymphatic system disorders Leukocytosis	12.0% 12/100 • Number of events 12 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	11.1% 11/99 • Number of events 11 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Cardiac disorders Atrial fibrillation	24.0% 24/100 • Number of events 24 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	17.2% 17/99 • Number of events 17 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Cardiac disorders Atrioventricular block	5.0% 5/100 • Number of events 5 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	2.0% 2/99 • Number of events 2 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Cardiac disorders Bradycardia	23.0% 23/100 • Number of events 23 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	12.1% 12/99 • Number of events 12 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Cardiac disorders Pericardial effusion	5.0% 5/100 • Number of events 5 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	5.1% 5/99 • Number of events 5 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Cardiac disorders Sinus tachycardia	4.0% 4/100 • Number of events 4 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	5.1% 5/99 • Number of events 5 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Cardiac disorders Supraventricular extrasystoles	8.0% 8/100 • Number of events 8 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	6.1% 6/99 • Number of events 6 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Cardiac disorders Tachycardia	21.0% 21/100 • Number of events 21 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	17.2% 17/99 • Number of events 17 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
General disorders Oedema peripheral	16.0% 16/100 • Number of events 16 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	15.2% 15/99 • Number of events 15 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
General disorders Pyrexia	38.0% 38/100 • Number of events 38 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	42.4% 42/99 • Number of events 45 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
General disorders Serositis	6.0% 6/100 • Number of events 6 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	5.1% 5/99 • Number of events 5 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Investigations Electrocardiogram ST segment elevation	5.0% 5/100 • Number of events 5 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	4.0% 4/99 • Number of events 4 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Investigations Hematocrit decreased	22.0% 22/100 • Number of events 22 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	6.1% 6/99 • Number of events 7 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Psychiatric disorders Disorientation	6.0% 6/100 • Number of events 6 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	1.0% 1/99 • Number of events 1 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Renal and urinary disorders Oliguria	7.0% 7/100 • Number of events 7 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	2.0% 2/99 • Number of events 2 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Respiratory, thoracic and mediastinal disorders Bronchospasm	3.0% 3/100 • Number of events 3 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	6.1% 6/99 • Number of events 6 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Respiratory, thoracic and mediastinal disorders Dyspnoa	6.0% 6/100 • Number of events 6 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	3.0% 3/99 • Number of events 3 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Respiratory, thoracic and mediastinal disorders Hypoxia	10.0% 10/100 • Number of events 10 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	10.1% 10/99 • Number of events 10 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Respiratory, thoracic and mediastinal disorders Increased bronchial secretion	9.0% 9/100 • Number of events 9 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	5.1% 5/99 • Number of events 5 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Respiratory, thoracic and mediastinal disorders Pleural effusion	47.0% 47/100 • Number of events 47 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	45.5% 45/99 • Number of events 45 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Skin and subcutaneous tissue disorders Subcutaneous emphysema	5.0% 5/100 • Number of events 5 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	0.00% 0/99 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Surgical and medical procedures Diuretic therapy	15.0% 15/100 • Number of events 15 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	15.2% 15/99 • Number of events 15 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Vascular disorders Hemorrhage	27.0% 27/100 • Number of events 27 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	23.2% 23/99 • Number of events 23 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Vascular disorders Hypertension	8.0% 8/100 • Number of events 8 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	10.1% 10/99 • Number of events 11 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Vascular disorders Hypotension	11.0% 11/100 • Number of events 11 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	13.1% 13/99 • Number of events 13 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.
Cardiac disorders Sinus bradycardia	0.00% 0/100 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.	7.1% 7/99 • Number of events 7 • From the time of the Recruitment Visit (Day -14) to the Follow-up Visit (Day 50 +/- 20 days) 206 subjects were randomized; six were screen failures. 199 subject were included in the Safety population (100 Anbinex and 99 control).One subject in the control group was excluded from the safety population as Anbinex was administered during the ICU stay.

Additional Information

Michael Ken Woodward, BSc, M.Sc

GrifolsTherapeutics Inc.

Phone: +1 919-316-6675

Email: michael.woodward@grifols.com

Results disclosure agreements

• Principal investigator is a sponsor employee Site may publish results from the Study, after providing Sponsor thirty days' notice prior to submitting a manuscript or other materials related to the Study to any outside party. At Sponsor's request, Site will remove any Confidential Information (other than Study results), and Site will upon Sponsor's request, delay publication or presentation for a period of up to one hundred twenty days to allow Sponsor to protect its interests in any Sponsor's Inventions.
• Publication restrictions are in place

Restriction type: OTHER